Basic principles of infectious diseases The term infectious diseases applies when an interaction...

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Basic principles of infectious diseases The term infectious diseases applies when an interaction with a microbe causes damage to the host and the associated damage or altered physiology results in clinical signs and symptoms of disease. So pathogen is defined as any microrganism that has the capacity to cause disease. Not all pathogens have an equal probability of causing disease in the same host population. Virulence provides a measure of pathogenicity: for example encapsulated pneumococci are more virulent than nonencapsulated pneumococci. Escherichia coli strains expressing Shiga-like toxin are more virulent than those that do not express these toxins

Transcript of Basic principles of infectious diseases The term infectious diseases applies when an interaction...

Page 1: Basic principles of infectious diseases The term infectious diseases applies when an interaction with a microbe causes damage to the host and the associated.

Basic principles of infectious diseases

The term infectious diseases applies when an interaction with a microbe

causes damage to the host and the associated damage or altered physiology

results in clinical signs and symptoms of disease.

So pathogen is defined as any microrganism that has the capacity to cause

disease.

Not all pathogens have an equal probability of causing disease in the same host

population.

Virulence provides a measure of pathogenicity: for example encapsulated

pneumococci are more virulent than nonencapsulated pneumococci.

Escherichia coli strains expressing Shiga-like toxin are more virulent than those

that do not express these toxins

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Opportunistic microrganisms

These microrganisms, usually do not cause disease in people with intact host

defence systems, on the contrary, they can cause devasting diseases in many

hospitalized and immunocompromized patients.

Most microrganisms with a capacity to multiply in humans (including members

of the indigenous commensal flora) cause disease more readily in individuals

with underlying chronic diseases or different compromises.

The term opportunist indicates well this category of pathogen.

Opportunistic pathogens a vary emergency in hospital are considered,

they are vehicolated by paramedical staff or assistance staff

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Interaction of pathogenic microrganisms with host

Adherence indicates the process by which the microrganisms bind to surfaces (initial interaction between pathogenic microrganism and host).

It is the first step of cellular invasion and toxins delivery process by microbial pathogens.

Adhesins are microbial surface molecules binding the organisms to host surfaces.

Capsules are formed by extracellular

polymeric substances. They inhibits

phagocytosis.

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Interaction of pathogenic microrganisms with host: other factors

Fibrillae are the fine “hairy” structures on bacterial cells.

Fimbriae are nonflagellar filamentous structures on bacterial cells.

Glycocalyx is a superficial polysaccharide-containing structure on cellular

surface.

Lectins are glycoproteins that inhibit specific binding to carbohydrates.

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Interaction of pathogenic microrganisms with host: receptors

Receptors are host molecules able to recognize and bind

the microbial adhesins.

A single adhesin may have more than one receptor, and a single

receptor may be recognized by many different adhesins.

The central role of adhesins in microbial colonization and

pathogenesis makes them ideal target for preventive and

therapeutic treatment

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Examples in which bacterial adherence correlates with bacterial virulence

Infection Organism Comments

Cystitis E. coli Infection correlates with adhesin type 1 fimbriae

Pyelonephritis E. coli Infection correlates with adhesin P fimbriae

Urethritis Strept. sanguis and other bacteria

Infection correlates with adhesins, fimbriae and type II outer membrane proteins.

Otitis media Streptococcus pneumoniae

Infection correlates with

adherence to pharyngeal epitelial cells

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Specific adherence mechanisms and their roles in pathogenesis

Microbial biofilmsMany of the studies of bacterial adherence have been done on free-floating

“planktonic” bacteria growing in culture.

In nature, however many bacteria exist in a complex community-like structure

known as Biofilm.

Biofilms are bacterial populations that are inclosed in a matrix of extracellular

polymeric substances.

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Microbial biofilms

Bacteria form microcolonies with conelike and mushroom-shaped morphologies by adhering to each other and to a surface.Water-filled channels surround the microcolonies and function somewhat like a primitivecirculatory system, allowing access to nutrients and interbacterial communication

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Microbial Biofilms

In the medical area biofilms are seen in native valve endocarditis, otitis media, dental plaque

and they are a problem for cystic fibrosis patients.

Biofilms also form on synthetic medical implants, including, intravascular

catheters, artificial valves, pacemakers, orthopedic devices and contact lenses.

Medical device Biofilm-associated microrganisms

Central venous catheter CN staphylococci, Staphyl aureus, Enteroc. faecalis,

Klebsiella pneum. Pseudomonas aeruginosa

Prosthetic heart valve, urinary catheters

Viridans streptococci, CN staphylococci, enterococci

S.aureus, E. coli, K. pneumoniae, Proteus mirabilis

Artificial valve prosthetic Streptococcus ssp. Staphylococcus epidermidis

Intrauterine device Staphylococcus aureus, epidermidis, enterococcus ssp

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Microbial Biofilms

One of the characteristics of Biofilms is their increased resistance to antibiotics.Bacterial biofilms have been reported to be up to 500 times more resistant to antibiotics thanplanktonic cells. There are several properties of biofilms that could contribute to increasedresistance to antibiotics. The esopolysaccharide matrix or slime that surrounds the cells may createan exclusion barrier to antimicrobials or inactive them. Bacteria in biofilms grow more slowly and slower growth may lead to decreased uptake of the drugs.

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Biofilms formation

Biofilms are formed in two phases. The first phase is an initial reversible adherenceto a surface. Several factors contribute, including surface hydrophobicity, proteic adhesins andcapsular polysaccharides.The second phase involves intracellular adhesion, which results in microcolonies formation andcomplex biofilm architecture

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Biofilms formationPili and flagella have been shown to be important in biofilms formations. Strains lacking flagellaappear unable to establish initial adherence to a substrate and microcolony formation.Elucidation of molecular mechanisms of biofilms formation should identify new targets for chemotherapy and provide new approaches to controlling biofilms formation.

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Respiratory tract infections

Respiratory tract infections may be devided into: upper and lower tract

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Upper respiratory tract infections

The common cold

Is the traditional term used to indicate a vary common syndrome of upper respiratory tract.Common cold is the most common infectious disease in humans (each adult contracts two to four infections a year, children may have six to ten cold a year).The major respiratory viruses causing colds are found in the family of rhinovirus myxovirus, paramyxovirus,adenovirus, piconavirus and coronavirus (the rhinovirus group accountsfor more than 50% of cases in adults). In total more than 200 different viral types cause colds.

A small number of colds is complicated by bacterial infections of the paranasal sinuses and themiddle ear, and require antimicrobial therapy.

Eyes congestion

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The common cold: incidence, signs and symptoms

Respiratory infections have a seasonal incidence (in the colder mounths, in

temperate areas and in rainy seasons they, more frequently, occur).

Signs and symptoms Symptoms are cough, sore throat, runny nose, nasal congestion accompanied

by headache, fatigue and loss appetite.

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The common cold: treatment

Not many commercial remedies provide a good symptomatic relief.The first-generation antihistamines and the nonsteroidal anti-inflammatory drugs (NSAID) are commonly used.Antihistamines are recommended in control of rinorrhea and nasal mucus.NSAID are used in reducing cough, probably through blocking prostaglandin action, and in control of headaches, malaise and other symptoms.

The combination of a first-generation antihistamines with NSAID provides a good relief in common cold

The development of a new vaccine is difficult, because many different viruses are implicated in common cold.

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Pharyngitis

Acute pharyngitis is an inflammatory syndrome of the pharynx caused by both

viral and bacterial agents.

Most cases are of viral etiology and occur as part of common cold and influenzal

syndromes.

The most important bacterial infections are due to the group A β hemolytic Streptococcus (Streptococcus pyogenes).It is important to differentiate streptococcal from viral pharyngitis because only bacterial forms are sensitive to penicillin.

Streptococcal pharyngitis may be complicated by acute rheumatic fever and acute glomerulonephritis.There are other uncommon or rare types of pharyngitis and for some of these, specific treatment is available

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Etiology: causes of pharyngitisEtiology syndrome/disease %

ViralRhinovirus Common cold 20coronavirus Common cold >5Influenza virus influenza 2

Epstein Barr virus Infectious mononucleosis <1

Cytomegalovirus Infectious mononucleosis <1

Bacterial

Streptococcus pyogenes Pharyngitis/tonsillitis 15-30

Mixed anaerobic bacteria Vincent's angina <1

Haemophilus influenzae Pharyngitis <1

Staphylococcus aureus Pharyngitis <1

Corynebacterium diphteriae Diphtheria >1

Mycoplasmal

Mycoplasma pneumoniae pneumonia <1

Unknown 40

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Pathogenesis

The pathogenetic mechanisms of pharyngitis are different in according to various etiologic agents.

In viral infections caused by adenovirus and coxsackievirus, direct invasion of pharyngeal mucosa occurs.

In infections caused by Streptococcus pyogenes, many factors influence colonization and invasion in host tissue (natural and acquired host immunity, interference by other bacteriapresent in the oropharynx, different M-types).

Streptococcus pyogenes elaborates a number of extracellular factors, including pyrogenicexotoxins, hemolysins, streptokinase, deoxyribonuclease, proteinase, hyaluronidase.

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Streptococcal pharyngitis

The severity of infections varies greatly.

In severe cases, there is marked pharyngeal pain, odinophagia and a temperatureof 39.4 °C.Headache and abdominal pain may occur; the pharyngeal membrane is fiery red,grayish-yellow exudate is presente on the tonsils.Enlarged, cervical nodes and a rise in the number of leukocytes are typical in acute suppurative bacterial infection

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Streptococcal pharyngitis: complications

Complications of acute streptococcal pharyngitis, may include: acute reumathic fever, acuteglomerulonephritis and invasive infections (meningitis, endocarditis etc)

There is a general association of specific M serotypes with these complications

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Scarlet fever

Infection with strains of Streptococcus pyogenes producing pyrogenic exotoxins causes scarlet fever. The body is covered by a characteristic erythematous rash followed by desquamation.The tongue is red, and the papillae are enlarged (strawberry tongue)

Characteristics of rash:

is fine and blanches upon pressureappareas 12-48 hours after the fevergenerally it starts on the chest

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Staphylococcal pharyngitis

Staphylococcus aureus causes pharyngitis

expecially in children (1% of cases)

Staphylococcal pharyngitis is

characterized by:

• Mucopurulent drainage

• Mucosal erythema

• Localized pustules

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Vincent's angina (Henry Vincent)

Vincent's angina also called: acute necrotizing ulcerative gingivitis is a mixed bacteria-spirochetal infection usually present in patients with poor dental hygiene and in immunocompromized patients.

Inflamed and ulcered gingivae and halitosis may characterize this form.Exudative tonsillitis, pharyngeal pain and dysphagia occurs. Septic emboli to the lung may lead to pulmonary abscesses and empyema.

Treatment includes irrigation and removal of necrotic areas, in untreated cases, infection canspread to the bones.

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Infectious mononucleosisPharyngitis often exudative occurs in many cases of infectious mononucleosis.The mononucleosis syndrome is caused by EBV or cytomegalovirus.Fever, fatigue, malaise, petechiae are present associated with headache.

Posterior and anterior cervical adenopathy is common and inguinal nodes are more frequently enlarged. Low-grade temperature and halitosis serves to differentiate this form from streptococcal pharyngitis.

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Diphtheria

Diphtheria still occurs in members of socio-economically disadvantaged populations.Human infection is caused by Corynebacterium diphtheriae. It colonizespharyngeal tract forming a characteristic tonsillar or nasopharyngeal pseudomembrane adherent to the tonsils and pharyngeal mucosa, causing bleeding and occlusion. Swollen neck is present. Patients may experience tiredness, pallor and fast heart rate.These symptoms are caused by the toxin released by bacterium.

The major damages include cardiac function withmyocarditis and peripheral neutropathy.The less severe forms are restricted to the skin (caracteristic lesions).Patients are treated with repeated course of antitoxin.Antibiotics are used in patients or in asymptomatic carriers to eradicate Corynebacterium diphtheriae,to reduce the numbers of bacteria and to prevent their trasmission.

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Diagnosis

The first objectives in diagnosis of acute pharyngitis are to distinguish cases of common viral etiology, which predominate, and do not require antimicrobial therapy, from those due to S. pyogenes or other unusual organisms for which treatment is available.

This distinction is critical because many patients continue to receive unnecessary antimicrobials increasing prescription for expensive broad-spectrum agents.

The presence of pharyngeal or tonsillar exudates, adenophaty or skin rash helps in differential diagnosis, but these findings are not specific in most cases

Several commercial kits are available for rapid detention ofgroup A streptococcal antigen from throat swabs. Rapid testsare 60-90% sensitive and 98-99%specific when comparedto colture methods.The patient's history and epidemiologic factors may help in suggesting a specific etiologic diagnosis in cases in which cultures or rapid antigen tests are negative for group A streptococci

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Treatment

Patients with Streptococcal pharyngitis should receive a 10-day dose of penicillin (or equivalent antibiotic). In allergic patients to penicillin erythromycin is recommended. Antibiotic treatment serve to prevent suppurative complications (peritonsillar abscess, sinusitis, otitis and pneumonia).

Vincent's angina: responds to an oral penicillin such as amoxicillin plus metronidazole or amoxicillin-clavulanate. Peritonsillar abscesses can be treated by surgical drainage or incision

Diphtheria: the treatment requires both antimicrobials and hyperimmune diphtheria antitoxin

Viral pharyngitis: amantidine or rimantidine can reduce symptoms in uncomplicated influenza, also neuroaminidase inhibitors have a similar effect.Acyclovir, valacyclovir and foscarnet are available for the treatment of ulcerative oropharyngeal Herpes simplex virus infection in immunocompromized patients

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Otitis

Otitis may be defined such as an inflammatory condition of the ear characterized

by pain, fever, abnormalities of hearing and vertigo.

Is devided into: externa and media otitis

Ear anatomy

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Otitis externa

Otitis externa: regards the outer ear (auricle pavilion and auditory canal).The esternal auditory canal is long 2.5 cm. The microbial flora is similar to floraof the skin (Staphylococcus epidermidis, S. aureus, Corynebacteria and anaerobic bacteria)

Infections of the external canal may be subdivided into four categories:

Acute localized otitis externa

Acute diffuse otitis externa

Chronic otitis

Invasive otitis externa

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Acute localized otitis externa

Acute localized otitis externa may occurs as a foruncle due to S. aureus

Pain is severeBluish, red hemorrhagic fluid may be frequent on auditory canal or on tympanic membrane, adenopathy is often present.Local treatment or systemic antibiotic treatment are curativeIncision or drainage are necessary in case of severe pain

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Acute diffuse otitis externa

Acute diffuse otitis externa (swimmer's ear) occurs in hot, humid wheathersThe skin is edematous and red. Gram negative bacilli especially Pseudomonas aeruginosa play an important role in etiology.Irrigation with hypertonic saline solution (3%), or cleansing with mixtures of alcohol and acetic acid may be used initially.A 10-day regiment of a fluorochinolone otic solution or ear drops associated with hydrocortisone serve to reduce local inflammation and to block infection.

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Chronic otitis externa

The most frequent cause of chronic otitis externa is chronic suppurative otitis media with perforated tympanic membrane.Rare causes include: tubercolosis, syphilis and sarcoidosis.

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Invasive otitis externaIs a severe necrotizing infection that spreads from the ear canal to adjacent areas ofsoft tissue, cartilage and bone.Frank pain and inflammation are accompanied by the drainage of pus from the canal.Diabetic, immunocompromized and debilitated patients are at particular risk.Pseudomonas aeruginosa is almost always the etiologic agent.Systemic therapy including anti-Pseudomonas drug should be used.Association of ceftazidime, cefepime or piperacillin with an aminoglycoside (gentamicin or tobramycin) should be considered.

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Otitis media

Otitis media is defined by the presence of fluid in the middle ear accompanied by signs orsymptoms

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Otitis media: epidemiology

Otitis media is a pediatric disease. The peak incidence occurs in the first 3 years of life.The highest incidence of acute otitis media occurs between 6 and 24 months of ageThe disease is less common in adolescens and adults

Children with acquired immunodeficiency syndrome have a higher incidence of otitismedia beginning at 6 months of age

Otitis media is infrequent in adults, but the bacteriology and therapy is similar to those in children

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Otitis media: pathogenesisThe middle ear includes: the nares, nasopharynx and eustachian tube.Anatomic or functional disfunction of the eustachian tube appears to play an important rolein the development of otitis media.

Eustachian tube has three physiologic functions:

Protection from nasopharyngeal secretions Drainage of secretions into the nasopharynx• Ventilation of the middle ear to equilibrate air pressure

When one or more of these functions are compromised, the result is the developmentof fluid and infection in the middle ear. Congestion of the mucosa of the eustachian tube mayresult in obstruction, and if bacterial pathogens are present a suppurative otitis can occur

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Etiology of otitis media

Bacteria

Streptococcus pneumoniae and Haemophilus influenzae are the most frequent cause in all age groups

Streptococcus pneumoniae is the most important bacterial cause of otitis media (a 7 valent conjugate polysaccharide vaccine serve to prevent this disease)

Haemophilus influenzae is a significant cause of otitis media in older children, adolescent and adults

Moraxella catarrhalis was isolated from 10% of children with acute otitis media. Before 1970, all strains of M. catarrhalis were sensitive to penicillin Today most strains produce β-lactamase and are resistant to penicillin ampicillin and amoxicillin

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Etiology of otitis media

Bacterial Pathogen Mean Range

Strep. pneumoniae 38 27-52

Haemoph. influenzae 27 16-52

Moraxella catarrhalis 10 2-15

Streptoc. pyogenes 3 0-11

Staphylococ. aureus 2 0-16

Miscellaneous 8 0-24

Viruses 28 12-35

Bacterial pathogens isolated from middle ear fluid in children with acute otitis media.Total percentages are greater than 100% because of multiple pathogens may be isolated

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Etiology of otitis media

Viruses

Many studies identify respiratory viruses or viral antigens in 25% of middle ear fluids ofchildren with acute otitis media.

The most important viruses found in middle ear fluids are:

Respiratory syncytial viruses

Influenza virus

Enteroviruses

Rhinoviruses

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Chlamydia and unusual organisms

Chlamydia trachomatis is associated with acute respiratory infections in infants younger than 6 mounths, and is a cause of acute infections of the middle ear in this age group

Uncommon forms of otitis include:

Diphtheritic otitis (bilateral form of otitis media with effusion due to diphtheria bacillus)

Tuberculous otitis (accounts for only 0.04% of all cases of chronic suppurative otitis media).

Otogenous tetanus (secondary to chronic ear infections)

Otitis due to Mycobacterium chelonae (chronic otorrhea and tympanic membrane perforation)

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Diagnosis and clinical course

Acute otitis media is defined by the presence of fluid in the middle ear accompanied by symptoms and acute illness.

Specific symptoms

Nonspecific symptoms

Ear painEar drainage

FeverLethargyIrritability

Signs and symptoms usually resolve with antimicrobial treatment

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Antimicrobial treatment

There are now 19 antimicrobial agents approved by the Food and Drug Administration for treatment of acute otitis media.Amoxicillin remains the drug of choice for initial treatment.The drug is ineffective against -lactamase-producing strains of Haemophilus influenzae andMoraxella catarrhalis (H. influenzae and M. catarrhalis are responsible for about 30% and 10% of acute otitis media cases respectively)

For patients with known and severe allergy to β-lactam antibiotics, a macrolide (erithromycin,azithromycin,or clarithromycin) is preferred.Decongestants, and corticosteroids administered alone or in combination with an antihistamine are used extensively for the treatment of otitis media with effusion.

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Sinusitis

• Sinusitis is an inflammatory condition of one or more of the paranasal sinuses (frontal, sphenoid, ethmoid,

• mascellar sinus)

• Most acute cases result from infection, other causes include allergy.

• Acute infectious sinusitis can be classified into various categories on the basis of different characteristics including the immune status of patient or its viral, bacterial or fungal etiology.

• The knowledge of these categories is important to understand the pathogenesis and to optimize the treatment of this disease. Paranasal sinuses anatomy

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Sinusitis: classificationSinusitis can be classified on the basis of symptoms persistence into

acute (symptoms persisting less than four weeks)

subacute (4-8 weeks)

chronic (8 weeks or more)

All three types of sinusitis have similar symptoms and are often difficult to

distinguish.

Sphenoid (not visible)

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Acute sinusitis

Acute sinusitis is often caused by an upper respiratory tract infection generally

of viral origin.

In case of bacterial infection, three are the most common etiological agents:

Streptococcus pneumoniae

Haemophilus influenzae

Moraxella catarrhalis

Until recently Haemophilus influenzae was the most common bacterial agent.

However introduction of the H. influenzae type B vaccine has decreased the

number of cases.

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Acute sinusitis: other causes

Other sinusitis causing bacterial pathogens include:

Staphylococcus aureus and other streptococci species

Anaerobic bacteria

Less common Gram negative bacteria

Viral sinusitis typically lasts for 7 to 10 days, bacterial sinusitis is more

persistent.

Acute episodes can also result from fungal invasion. These infection are

typically seen in patients with diabetes or other immune deficiencies syndromes

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Subacute sinusitis

Subacute sinusitis: infection is present for more than four but less than eight weeks. Symptoms may be less severe and include nasal congestion or post-nasal drip.

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Chronic sinusitis

Chronic sinusitis, by definition, lasts more than three months and can be caused by different diseases. Symptoms may include any combination of nasal congestion, facial pain, headache,night-time coughing, general malaise etc.Often chronic sinusitis can reduce sense of smell.

In a small number of cases chronic sinusitis is associated with a dental infection

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Chronic sinusitis: complicated casesChronic sinusitis cases are subdivided into cases with polyps and cases without polyps.When polyps are present (ethmoid or mascellary sinuses), the condition is more severe.Abnormally narrow sinus and deviated septum blocks the drainage from the sinus cavitiescontribuiting to infections.A combination of anaerobic and aerobic bacteria including Staphylococcus aureus and coagulase-negative staphylococci can occur. Also fungi play an important role in this disease(fungi can be found in the nasal cavities and sinuses of most patients with sinusitis).Antibiotic treatment provide a reduction of inflammation.

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Treatment of sinusitis

Nasal irrigation may help in cases of chronic sinusitis, decongestant sprays may

provide relief.

Antibiotic treatment

Most cases of sinusitis are caused by viruses and resolve without antibiotics.

If symptoms do not resolve within 7 days, amoxicillin/clavulanate (Augmentin)

is used.

Fluoroquinolones and macrolide antibiotics are indicated in patients

allergic to penicillins.

Corticosteroids

Intranasal corticosteroids are used in combination with antibiotics.

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Lower tract respiratory infections

Bronchitis

Bronchitis is an inflammatory syndrome of the tracheobronchial tree. It occurs most often during the winter months, when respiratory tract infections are prevalent.May be divided in acute and chronic.

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Acute bronchitis: clinical finding and etiology

Cough occurs in approximately 50% of cases of acute bronchitis. The symptoms are most requently associated with fever. (Members of all the major respiratory virus groups often cause cough and bronchitis, in fact, cases of acute bronchitis are particularly common during epidemic influenza)

A small number of all cases of acute bronchitis have a nonviral cause.

Mycoplasma pneumoniae and Bordetella pertussis play an important role.

In adolescens and adults Bordetella pertussis has been associated with 12 to 32% of cases.

Also Chlamydia pneumoniae has been associated with cases of acute bronchitis

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Treatment

Symptomatic treatment

Treatment of most cases of acute bronchitis is symptomatic and is directed primarily at thecontrol of cough. Patients do not require hospitalization except in cases of unusual severity

Antimicrobial treatment

Antimicrobial treatment is recommended for cases of acute bronchitis caused by Bordetella pertussis, Mycoplasma and Chlamydia pneumoniae.Mycoplasma pneumoniae infections are treated with erithromycin or tetracycline.Bordetella pertussis infections with erythromycinChlamydia pneumoniae with tetracycline, erithromycin or azitromycin

Antimi

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Chronic bronchitis and obstructive pulmonary disease

Chronic bronchitis is a chronic inflammation of the bronchi in the lungs.It is considered one of the two forms of chronic obstructive pulmonary disease (COPD), clinically defined as a persistent cough producing sputum and mucus for at least three monthsper year. COPD is a severe form characterized as airflow limitation. Occasionally chest pain fever and malaise may occur.Superinfections can coexist, causing exacerbation of COPD. Mucus is often green and also may be orange or pink, depending on the pathogen causing the inflammation.

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Epidemiology and etiology of COPD

Over the past several decades, the prevalence of Chronic Obstruc.Pulmon.Dis.

has increased in wordlwide, especially in industrialized countries and in women

Multiple factors can cause COPD:

tobacco smoking is considered the major cause in industrialized countries

cystic fibrosis caused by a gene defect in the transmembrane conductance

immunoglobulin deficiency (IgA or selective IgG subclasses or both)

structural or acquired defect in cilia

air pollution

Allergies can also cause mucus hypersecretion, leading to symptoms similar to asthma

or bronchitis

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Microrganisms implicated in acute exacerbation of COPD

An exacerbation of COPD or chronic bronchitis is signaled by an increased

volume of more purulent sputum, cough and dyspnea.

Bacterial bronchial airway colonization includes:

Streptococcus pneumoniae, Haemophilus influenzae, Neisseria ssp.

Also respiratory viruses have been associated with asthmatic exacerbation

(one third were related to viral infections) such as Rhinoviruses, coronaviruses

and parainfluenzaviruses)

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Antibiotic therapy

Many consideration must guide the selection of appropriate antibiotic therapy

including spectrum of activity, mechanism of action, tissue penetration,

tolerance of the drug by the patients.

Antimicrobial choice must be made in the context of emerging antibiotics

resistance.

Currently most patients receive: amoxicillin clavulanate

erithromycin

levofloxacin

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Acute pneumonia

This is a section of the lungs in a patient affected by pneumonia. The neutrophils appear to be floating in space

Acute pneumonia is the sixth most common cause of death in USA and the most commoncause of infection-related mortality.A wide number of microbial agents can cause acute pneumonia, and no a single antimicrobial regiment can be expected to cover all possibilities, because a specific etiologic diagnosis is often not possible.In addition the prevalence of antibiotics resistant strains has made this challenge more difficult

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Etiological agents of acute pneumonia: bacteria

Streptococcus pneumoniae

Staphylococcus aureus

Anaerobic bacteria: bacteroides,fusobacterium ssp

Haemophilus influenzae

Enterobacteriacee:

Escherichia coli

Klebsiella pneumoniae

Enterobacter

Serratia

Pseudomonas aeruginosa

Legionella pneumoniae

Acinetobacter

Neisseria meningitidis

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Less common agents of acute pneumonia: Fungi, Rickettsia, Chlamydia etc.

Aspergillus ssp

Candida albicans

Candida ssp

Coccidioides immitis

Cryptococcus neoformans

Histoplasma capsulatum

Coxiella burnetii Q fever stands for queer, is a zoonosis (contact with

infected animals

Rickettsia rickettsiae puncture of tick

Chlamydia psittaci caused by infected birds (parrots ducks)

Chlamydia pneumoniae pneumonia often asymptomatic in young p.

Chlamydia trachomatis causes ocular or genital infections

Mycoplasma pneumoniae causes an atypical form of pneumonia in

young population

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Causative agents of acute pneumonia: viruses

Children

Common

Respiratory syncyntial virus

Parainfluenza virus types 1,2,3.

Influenza A virus

Uncommon

Adenovirus, Rhinovirus

Adults

common

Influenza A and B

Uncommon

Rhinovirus

Enterovirus

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Community-acquired pneumonia

Acute Community-Acquired pneumonia

A long list of bacterial, fungal, viral agents may cause this syndrome.

Patients with acute community-acquired pneumonia are usually in their mid-fifties to late

sixties.

Peak incidences in midwinter and early spring have been described, so there is no

“pneumonia season” but disease takes place at all time.

Most patients (60% to 90%) have one or more chronic diseases, cardiovascular diseases

neurological diseases, diabetes. Immunosuppression related to myelosuppressive agents

or HIV infection may be present in more than 57% of patients. (patients affected by HIV

infection are treated with myelosuppressive agents and develop pneumonia in many

cases

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Acute Community-Acquired Pneumonia: signs and symptoms

Community-acquired pneumonia presents with a sudden onset of a chill followed by fever

chest pain and cough producing mucopurolent sputum.

The signs, symptoms and physical findings vary according to the age of the patient.

These classic findings in some combination are present in approximately 81% of patients

with community-acquired pneumonia for a mean of 6 days.

Cough is noted in greater than 80 to 90% of patients and is often productive.

A variety of nonrespiratory symptoms are associated with pneumonia, including anorexia,

sweats and nausea.

Tachypnea (more than 30 breaths per minute) is noted in older age groups.

The white blood cells (15,000 to 35,000/mm3), also positivity in C-reactive protein is

noted early

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Acute Community-acquired pneumonia. Signs and symptoms

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Acute Community-Acquired Pneumonia: infectious agents

In the past 50% to 90% of cases were caused by Streptococcus pneumoniae.

More recently the importance of S. pneumoniae has varied showing from 16 to 60%.

Advanced age, cigarette smoking, diabetes, chronic illnesses, have been indicated as

significant risk factors for the development of pneumococcal pneumonia.

An estimated 3% to 38% of cases of ACAP are caused by Haemophilus influenzae

(the true incidence is obscured by the difficulty to isolate it from sputum).

Staphylococcus aureus accounts for 2 to 5% and takes an increase importance in older

patients or in those with influenza.

Gram negative rods account for 7 to 18% of cases. Half of these cases are caused by

Pseudomonas aeruginosa. Gram negative rods are particularly important in hospitalized patients

and immunocompromized patients

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Acute Community-Acquired Pneumonia: infectious agents

Streptococcus pneumoniae Pseudomonas aeruginosa

S. aureus

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Acute Community-Acquired Pneumonia: other agents

• The importance of Legionella species varies in different geographic areas.

• No clinical signs distinguish legionella species pneumonia from that caused by other bacteria

• However the presence of a high fever, male sex, elevated liver enzyme levels, have all

been associated with Legionella pneumoniae.

• Moraxella catarrhalis has been also identified as a cause of pneumonia.

• The incidence is low, but Moraxella catarrhalis appareas an important pathogen in older adults with Chronic Obstructive Pulmonary Disease or in immunocompromized people.

Moraxella catarrhalis

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Community-Acquired Pneumonia: in the older adults

Pneumonia is the third most common cause for hospitalization in those 65 and older,

and a major cause of morbidity and mortality may be considered.

Fever less commonly in older adults (especially over 80) occurs, temperature is variable,

but tachypnea more frequently is observed.

In general the etiological agents of community acquired pneumonia in older people

are similar to younger populations: S. pneumoniae is the predominant

organism (20 to 60% of cases). H. influenzae is the second most common agent.

Increased oropharyngeal colonization with Gram negative rods has been documented

in the older population, so a predisposition to develop pneumonia has been noted in

these subjects

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Community-Acquired Pneumonia: in Patients with AIDS

Pneumocystis carinii infection remains a significant problem in patients with AIDS.

Many studies suggest that Pneumocystis accounts for over one third of cases of

pneumonia in HIV-positive populations.

The cases of pneumonia can be 100 to 300 times greater in HIV infected patients than in

non-HIV infected controls.

A variety of other microrganisms have been implicated, including:

Rhodococcus equi (intracellular Gram positive organism, it infects animals occasionally

humans are infected, especially immunocompromized patients)

Pseudomonas aeruginosa especially in presence of central venous or urinary catheters.

Mycobacterium tuberculosis and nontuberculous mycobacteria,

Cryptococcus neoformans

Cytomegalovirus

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Pneumocystis carinii

Pneumocystis carinii a fungal organism or a protozoa is considered

(unconfirmed taxonomy)

Asymtomatic infection is common in infant (confirmed by level of specific

antibodies in population).

Pneumonia in AIDS patients a riattivation of infection and no a new

infection is considered

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Community-Acquired Pneumonia: in Patients with AIDS

Criptococcus neoformans

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Severe Community-Acquired Pneumonia

Approximately 10% of community acquired pneumonia cases are severe and required

intensive care and/or mechanical ventilation.

Advanced age, presence of other significant diseases (including pulmonary diseases),

congestive heart failure, genetic predisposition, appear to be associated with the

development of severe community-acquired pneumonia.

Streptococcus pneumoniae and Legionella pneumophila are the organisms more

frequently involved.

Gram negative rods, especially klebsiella species must be considered in patients affected

by Chronic Obstructive Pulmonary Diseases, diabetes and in case of alcohol abuse.

Mortality rates have ranged from 20% to 50%.

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Severe Community-Acquired Pneumonia

Klebsiella pneumoniae on Mc Conkey agar

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Atypical pneumonia syndrome

In 1938 Hobart Reiman described a mild clinical form of atypical pneumonia

characterized by fever malaise, headache, cough without sputum.

Mycoplasma pneumoniae, Chlamydia pneumoniae, Francisella tularensis and a

variety of respiratory viruses may cause atypical pneumonia.

Mycoplasma pneumoniae infections in the older child (older than 5 years), in the

adolescent and in the young adult occurs. Mycoplasmal infection occurs at all time but,

an increased incidence is noted in the late summer and autumn, in contrast

Adenovirus infection, another cause of atypical pneumonia, most commonly occurs

between January and April

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Francisella tularensis

• Francisella tularensis is Gram negative intracellular parasyte.

• It is the etiological agent of tularemia, a zoonosis called rabbit fever.

• Bacterium can infect rabbits and other small animals.

• Infection can be transmitted to humans by a puncture of ticks (vector) or by inhalation of bacteria.

• Infection of the skin is observed (75-80% of cases ) after a contact with infected animals (ulcerated areas)

• In course of tularemia also a form of atypical pneumonia occurs.

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Antibiotic therapy in Community-Acquired Pneumonia

The choice of antibiotic is complicated by the increasing incidence of drug resistance in

pneumococci.

The incidence of penicillin nonsusceptibility (MIC ≥0,12) has increased dramatically since the 1970.

Surveillance studies between 1979 and 1987 shoved high levels of incidence of

Penicillin nonsusceptibility. By the early 1990 the incidence has increased to 20% and by

the winter of 1999-2000, 34,1% of pneumococchi strains were nonsusceptible and 16%

were resistant to penicillin (MIC<2).

Oral cephalosporins such as cefuroxime appears to be the most potentially usefull, but

only for penicillin-intermediate strains (from 0,125 to 2) of pneumococci.

Parental penicillin or third-generation cephalosporins (ceftriaxone or cefotaxime) are

used for resistant strains.

Vancomycin, linezolid, quinupristin/dalfopristin are considered when etiologic agent is

meticillin resistant Staphylococcus aureus (MRSA)

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Pneumonia prevention

• Vaccination against influenza virus and against S. pneumoniae serve to prevent pneumonia.

• In older adults, influenza vaccine decreases the incidence of pneumonia by 53%.

• Pneumococcal polysaccharide vaccine is recommended for patients older than 65.

• Protein polysaccharide vaccine is available only for pediatric use (conjiugated vaccine).

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Chronic pneumonia

• Chronic pneumonia is a pulmonary parenchymal process caused by infectious or noninfectious agents, that has been present for weeks to months, characterized by abnormal radiografic findings and chronic or progressive pulmonary symptoms.

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Chronic pneumonia: etiology

The infectious causes of chronic pneumonia can be divided into two main groups:

1) Agents that typically cause acute pneumonia and are unusual causes of chronic

pneumonia

2) Infectious agents that typically cause chronic pneumonia.

Many agents typically causing acute pneumonia such as: anaerobic bacteria,

Staphylococcus aureus, Haemophilus influenzae, enterobacteriacee and

Pseudomonas aeruginosa, most likely produce a persistent chronic pneumonia.

This is a chronic necrotizing process that most commonly occurs in patients

with significant diseases (alcoholism, diabetes mellitus, hospitalized patients, individuals

requiring ventilatory assistance etc.)

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Chronic pneumonia: etiology

Infectious agents that typically cause chronic pneumoniaAerobic and anaerobic bacteria:

Actinomyces responsable of chronic abscesses

Nocardia

Rhodococcus equi

Burkholderia ssp

Mycobacteria (tuberculosis, avium complex)

Fungi:

Aspergillus ssp

Cryptococcus neoformans

Coccidioides ssp

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Burkholderia cepacia complex

Burkholderia cepacia complex is a group of Gram negative, catalase positive

and lactose non fermenting species (nine species). This microrganism causes

pneumonia in immunocompromized patients and lung disease in patients

affected by cystic fibrosis or chronic granulomatosis disease.

Pathogenesis: organisms may be found in water or in soil and can survive in wet

areas, also person to person spread has been documented.

Infection can cause a rapid decline in the lung function resulting in death.

B. cepacia complex is naturally resistant to many common antibiotics including

Aminoglicosides or Polimixyn B (used for identification of organism: polymixin

bacitracin lactose agar)

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Chronic pneumonia: noninfectious causes

However it is important to recognize the importance of non infectious causes

of chronic pneumonia including:

Neoplasia (carcinoma, lymphoma etc.)

Drugs

Radiations

Amyloidosis (deposit of amiloid proteins in organs or tissue such as heart, intestine)

Sarcoidosis (abnormal collection of inflammatory cells in many organs)

Other idiopathic causes

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Chronic pneumonia in people with AIDS

• In persons with acquired immunodeficiency syndrome this infection is frequently seen. In these patients, chronic pneumonia may be caused by Rhodococcus equi, Pneumocystis ssp, Cytomegalovirus or by noninfectious disorders as Kaposi’s sarcoma, lymphoma, radiation therapy etc.

• Since the introduction of antibiotics in the 1940s, new pathogens have emerged. Organisms considered to be commensals are now recognized

as pathogens. R. equi produces large and mucoid colonies. Initially the colonies are greyish but after further incubation may appear salmon in colour.

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Chronic pneumonia: therapy

In many patients, etiologic agents do not are identified only on the basis of Gram stain or

cultural methods, but definitive diagnosis requires serologic, histologic, bacteriologic

studies or other diagnostic tests.

In this situation, immediate empirical therapy is recommended, the choice of antimicrobial

agents must be based according to epidemiologic or clinical data.

Empirical therapy with the newer fluoroquinolones (levofloxacin, moxifloxacin

etc) may be performed

In patients, affected by chronic pneumonia, intubated in an intensive care unit,

antimicrobial therapy should provide broad-spectrum coverage against hospital-acquired

flora including anaerobes, Staphylococcus aureus and aerobic Gram negative bacteria

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Corticosteroids in chronic pneumonia

The use of corticosteroids in the treatment of patients with chronic pneumonia is controversial.

Steroids are not indicated in case of pneumonia caused by infectious agent .

Generally corticosteroids only in chronic pneumonia due to noninfectious causes are used.

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Cystic fibrosis

Cystic fibrosis is caused by a mutation in the gene encoding for the protein cystic fibrosistransmembrane conductance regulator (CFTR). This gene is required to regulate the components of sweat glands, the production of digestive juices, and mucus. Cystic fibrosis determines superinfections of the lungs, compromizes the function of the pancreas, liver , intestine, and sex organs.The mucus clogs the lungs causing breathing problems and bacterial infections with conseguent lung damage

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Cystic fibrosis: clinical manifestations

The clinical manifestations of cystic fibrosis are related to viscous secretions

and chronic bacterial infection of the lung. More than 90% of cystic fibrosis

deaths are caused by the progressive pulmonary insufficiency.

Most respiratory bacterial infections in adults are caused by Staphylococcus

aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex.

The clinical finding is dominated by a chronic cough characterized by purulent

sputum, dyspnea anorexia and weightless.

Most adults may exhibit low-grade fever, sepsis or bacteremia.

Despite the large number of bacteria in sputum, other complications

(hemoptisis or pneumothorax) frequently occur.

Hemoptisis is expectoration of blood from the bronchi.

Pneumothorax is a collection of air or gas in pleural cavity in course of trauma or

surgical treatment

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Cystic fibrosis: other complications

• The pancreas is particularly involved in cystic fibrosis; most patients show a progressive destruction of organ.

The prevalence of diabetes mellitus increases in adults.

• The diabetic condition increases the predisposition to pulmonary infections

and makes difficult the treatment.

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Cystic fibrosis: microbiology Staphylococcus aureus and Pseudomonas aeruginosa are the primary

etiological agents of pulmonary infection in patients with cystic fibrosis.

S. aureus can be found in about 30% of patients with CF. Antistaphylococcal

penicillins (methicillin and isoxazolil-penicillins) are used to control infections

caused by this microrganism.

Resistance to these antibiotics is increasing in patients with CF (10 to 30% are

infected with methicillin-resistant Staphylococcus aureus MRSA).

A further problem in CF patients with MRSA infection is the emergency of

strains with reduced vancomycin susceptibility

Small colony variants of S. aureus are recognizedwith increasing frequency in patients with CF orchronic osteomyelitisThe variant shows a higher survival to cell mediated immunity

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Cystic fibrosis: microbiology

• More than 80% of adolescent and adult patients with CF, presents a chronic infective

state caused by Pseudomonas aeruginosa.

• Strains of P. aeruginosa isolated from these patients produce a large amounts of

an extracellular mucoid polysaccharide called alginate (mucoid colonies that result

from alginate production are predominant in patient with CF and are rarely seen in

patient with other chronic diseases)

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Pseudomonas aeruginosa and antibiotic resistance

In the early stage of cystic fibrosis infection Pseudomonas aeruginosa strains

are usually susceptible to all antipseudomonal β-lactams, imipenem, quinolones

and aminoglycosides.

Repeated antibiotic treatments and selection of chronic mucoid strains,

Increases antibiotic resistance.

Two factors occur to determine antibiotic resistance:

1) growth as a biofilm

2) growth under anaerobic conditions

Many studies have shown that P. aeruginosa growing as a biofilm is much more

resistant to antibiotics, in addition the capacity to grow under anaerobic

conditions increases the resistance against the aminoglycosides (inactive under

anaerobic conditions)

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P. aeruginosa growing under anaerobic conditions

Proteomic analysis has indicated an outer

membrane protein, upregulated in

anaerobic condition and able to reduce the

accumulation of toxic products of anaerobic

respiration.

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Cystic fibrosis: microbiology

• Burkholderia cepacia is an emerging important nosocomial pathogen isolated from 10% of patients with CF.

• Many patients with CF and infected with B. cepacia develop the cepacia

syndrome characterized by a rapid deficiency of pulmonary function and

bacteremia (these patients die within 6 mounths).

The ability to biofilm formation play an important role in resistance against

antibiotics.

• Burkholderia cepacia is a frequent cause of infection in patients with transplanted lungs.

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Cystic fibrosis: microbiology

Other bacteria such as Haemophilus influenzae, Moraxella catarrhalis,

Stenotrophomonas maltophilia and members of enterobacteriacee have been

isolated from the respiratory tract of patients with cystic fibrosis and may play a

role in their pulmonary disease.

In this period, the life expectancy is increasing and more patients with CF

survive, so multidrug-resistant microrganisms such as S. maltophilia are seen

with increased frequency.

The role of Mycobacteria in the lung disease of patients with CF has been

observed. Nontuberculous mycobacteria have been isolated in more than 13%

of patients with CF (72% were Mycobacterium avium complex, 18%

Mycobacterium abscessis)

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Cystic fibrosis: (oral therapy)

The aim of therapy is to retard progressive lung demage by removing viscous

and purulent secretions, by bloking person-to-person spread of drug-resistant

organisms frequently noted in CF affected patients.

Antibiotic treatments play a key role in survival. Oral antibiotics can be used to

treat subacute pulmonary exacerbation, despite the presence of

Pseudomonas aeruginosa (resistant to these antibiotics).

Antibacterial therapy, in this case, inhibits the release of toxic bacterial

exoproducts also in absence of bacterial killing.

The emergency of bacterial resistance during monotherapy limits the efficacy

of long-term treatment.

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Cystic fibrosis: (parental therapy)

Parental therapy is indicated for clinical exacerbations that do not respond to

oral antimicrobials.

Parental therapy should be guided by bacteriologic analysis of sample and

susceptibity tests to antibiotics.

A combination of antibiotics is indicated to treat infections caused by

Pseudomonas aeruginosa. The pharmacologic regimen usually includes an

aminoglycosides plus another agent active against P. aeruginosa such as a

Cephalosporin (ceftazidime or cefepime).

In case of Staphylococcus aureus infection addition of specific antistaphylo-

coccal agents should be considered

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Urinary tract infections:definition

• Urinary tract infection is an infection regarding the urinary system.

• Urinary system includes the upper (Kidneys, ureters) and the lower tract (bladder and urethra).

• Any part of urinary system can become infected, but most infections involve the

lower urinary tract (bladder and urethra).

• Women are at particular risk to develop urinary tract infection (1:5).

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Urinary tract infections: definition

Bacteriuria is a frequently used term to indicate the presence of bacteria in the

urine.

The presence of infected urine in the bladder can be discovered by quantifying

the bacteria in collected urine or in urine obtained via uretral catheterization.

The term “significant bacteriuria” indicates that the number of bacteria

exceeds the number expected from normal contamination.

Asymptomatic bacteriuria refers a significant bacteriuria in patients without

symptoms.

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Urinary tract infections

Urinary tract infection may involve onlythe lower urinary tract or may involve boththe upper and the lower tract.

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Lower urinary tract infections: cystitis

Cystitis is an infection of the urinary bladder.

This condition more often affects the women, but can regard either sex and all

age groups.

There are several types of cystitis:

1) traumatic bacteria are transferred from the intestinal

tract to the bladder

2) radiation patients treated with radiation therapy

3) hemorragic blood in urines

4) eosinophilic rare form, the bladder wall is infiltrated

with a high number of eosinophils

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Cystitis: causes and incidence

Cystitis occurs when the normally sterile lower urinary tract is infected by

bacteria and becomes irritated and inflamed

This condition affects sexually active women ages (20 to 50) but may occur in

not sexually active women or in young girls. Older adults are a high risk for

developing cystitis.

Cystitis is rare in males.

Females are more exposed because of their relatively shorter urethra and the

relatively short distance between the opening of the urethra and the anus

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Cystitis: risk factors

Risk of cystitis increases in presence of:

obstruction of the bladder or urethra (congenital abnormalities)

insertion of instruments (catheterization or cystoscopy)

Pregnancy (urine discharge becomes difficult)

Diabetes (urines contain more sugar favouring the growth of bacteria)

Analgesic nephropathy (damage induced by use of aspirin, paracetamol)

Reflux nephropathy (urine is forced back toward the kidney)

Older males develop cystitis associated with a condition of benign

prostatic hyperplasia, prostatitis and abnormalities of urethral structure

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Reflux nephropathy

Normally, when the bladder empties, theureter closes automatically

In reflux, the valves don’t close and urineis forced back toward the kidney

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Cystitis: infecting organisms

More than 95% of lower urinary tract infection are caused by a single bacterial

species. Escherichia coli is the most frequent infecting organism in acute

forms.

In recurrent urinary tract infections, especially in presence of structural

abnormalities (obstructive uropathy, congenital anomalies) the frequency of

infection caused by Proteus, Pseudomonas, Klebsiella, Enterobacter

enterococci and staphylococci increases

In presence of structural anomalies it is relatively common to isolate

multiple organisms from the urine.

Instrumentation and repeated courses of antimicrobial therapy play an

important role in selection of antibiotic-resistant organisms.

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Cystitis: infecting organisms in hospital environment

The hospital environment influences the etiology of urinary tract infections.

Proteus, Klebsiella, Enterobacter, Pseudomonas ssp, staphylococci and

enterococci are more often isolated from hospitalized patients, on the contrary

E. coli is the most frequent in community.

Cross-infections are important in the pathogenesis of hospital-acquired urinary

tract infections, especially related to catheters introduction.

Corynebacterium urealyticum, staphylococcus saprophyticus and other

coagulase-negative staphylococci have been recognized as important

nosocomial pathogens.

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cystitis: symptoms

Pressure in the lower pelvis

Painful urination (dysuria)

Frequent urination (polyuria)

Need to urinate at night

Abnormal urine color (cloudy)

Blood in the urine (hematuria)

Strong urine odor

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Cystitis: tests

In case of cystitis:

• urine analysis urine analysis commonly shows an

increased number of white blood cells or red blood cells.

• urine culture A sample of urine or a speciment of catheterized urine are collected

for identification of infecting organism and to select the

specific antibiotic treatment. Dip slide urine culture device

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Cystitis: treatmentAntibiotic treatment is important in the control of infection and

in prevention of recurrent forms.

Conventional therapyIn the past, 7 to 10 days of therapy were recommended for patients with lower

tract infections. In recent years it has become clear that most women have only

a superficial infection and can be treated with shorter courses of therapy,

sometimes with only a single dose of an antimicrobial agent.

Short-Course therapyShort-course therapy is defined as 3 or fewer days of treatment.

The advantages include a better compliance and a decreased risk for

emergence of multi-resistant organisms in intestinal, urethral or vaginal flora

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Cystitis: short-course therapy

Short-course therapy

The most widely used regiments are the oral doses of amoxicillin.

Other regiments include, aminoglycosides, tetracycline, cephalosporins and

fluoroquinolones.

Because of the high cost of the fluoroquinolones and more rapid emergency of

bacterial resistance with their wide-spread use, clinisians may prefer to use

Trimethoprim-sulfamethoxazole. This agent must be used in case of susceptible

infecting organisms or in patients do not receiving recent antimicrobial therapy.

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Cystitis: Fungal origin

Candida ssp vary often can cause infection in catheterized patients.

Catheters must be removed in 30 to 40% of subjects with candiduria.

Continuous amphotericin B bladder irrigation or oral fluconazole (200 mg for 7

days) in association with removing catheter serve to eliminate candiduria.

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Complicated urinary tract infection

Complicated urinary tract infection indicates an infection caracterized by

functional or structural anomalies (catheters, calculi, malformations).

In general infection in men, pregnant women, children or hospitalized

patients may be considered complicated.

In these cases, relapses or reinfections can occur.

Relapse is a bacteriuria with the same infecting microrganism.

Reinfection is a bacteriuria with a different microrganism from the original

infecting bacterium.

In patients with complicated infection, infecting microrganisms become

more often resistant to antimicrobial agents.

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Reinfection of the urinary lower tract

Many patients can develop frequent reinfections of the urinary lower tract, in

these cases, when symptoms are severe, long-term chemoprophylaxis is

recommended.

If reinfection occurs in course of therapy, the prophylactic agent must be

changed.

Long-term chemoprophylaxis should be considered in patients at risk to

develop renal parenchymal damage (e.g. young children or adults with

obstructive uropathy).

Fluoroquinolones and other antimicrobial agents are used with good

results

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Acute pyelonephritis: upper tract

• Acute pyelonephritis describes a clinical syndrome characterized by frank pain and fever often associated with dysuria, urgency and frequency.

• More frequently this syndrome is accompanied by significant bacteriuria and

acute infection of the kidney

In severe pyelonephritis the Kidneyis enlarged.Renal surface is covered byvariable numbers of smallyellowish, abscesses surrounded by zone of hyperemia

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Acute pyelonephritis: infecting organisms

Adhesive properties of the organisms are involved in selection of bacteria able

to colonize and infect upper urinary tract.

Humans studies have confirmed the significance of the adhesive capacity of the

urinary pathogens in pathogenesis of upper tract infections.

Pyelonephritis E. coli strains, adhere more strongly to uroepithelial cells, with

filamentous organelles called pili or fimbriae.

P fimbriae are frequently present in uropathogens E. coli.

In addition to P fimbriae a variety of adhesins have been identified on

uropathogenic E.coli

Other uropathogen microrganisms such as Proteus mirabilis and Klebsiella

ssp. have demonstrated the importance of adherence in pathogenesis of urinary

infections.

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Acute pyelonephritis: antimicrobial therapy

Patients with severe pyelonephritis should be hospitalized.

In patients with acute community-acquired pyelonephritis, when Gram-negative

bacilli are suspected, empirical therapy includes a wide number of antimicrobial

agents: aminoglycosides, piperacillin-tazobactam, third-generation

cephalosporins (cefotaxime or ceftriaxone) or parental fluoroquinolones.

In patients with hospital-acquired Gram-negative infection the possibility to

isolate multi-resistant organisms increases.

Ceftazidime, cefepime, piperacillin-tazobactam, meropenem or ertapenem often

in combination with aminoglycosides are recommended.

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Chronic pyelonephritis

• In chronic pyelonephritis one or both kidneys are involved.

• The anatomo-pathologic exam shows inflammatory changes in the pelvic wall, with papillary atrophy.

• The parenchyma shows interstitial

fibrosis with an inflammatory infiltrate of lymphocytes, plasma cells and occasionally neutrophils.

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Central nervous system syndromes

• The central nervous system may be infected by a variety of agents, including viruses, bacteria, fungi, protozoa.

• In addition a number of noninfectious disorders may regard the CNS

such as: neoplastic diseases, intracranial tumors, vascular disorders etc.

• All central nervous system diseases are associated with significant morbidity and mortality.

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Meningitis

Meningitis is an inflammation of the protective membranes covering the brain and spinal cord(meninges), identified by an abnormal number of white blood cells in cerebrospinal fluid (CSF)

meningitis in acute or chronic form can occur.

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Acute meningitis

Acute meningitis is clinically defined as a syndrome characterized by

meningeal symptoms that occur sudden or after several days.

The most common symptoms are severe headache (90% of cases) followed by

nuchal rigidity (70% of cases) associated with fever, confusion, vomiting and

inability to light tolerate (photophobia).

Sometimes especially in small children, only non specific symptoms may be

present such as irritability.

Chronic meningitis is characterized by signs and symptoms lasting for more

than 4 weeks.

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Acute meningitis

The acute meningitis syndrome may be caused by a wide variety of infectious

agents but may be caused also by noninfectious agents.

Aseptic meningitis

Viruses are the major cause of the aseptic meningitis syndrome, a term used

to define any meningitis (infectious or noninfectious) for which the etiologic

agent is not defined with stain or cultural methods of CSF and characterized by

lymphocytic pleocytosis.

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Acute meningitis: viral agents

Nonpolio enteroviruses

Arboviruses

Herpesviruses

Human immunodeficiency virus

Adenovirus

Parainfluenza virus

Influenza virus

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Acute meningitis : major bacterial agents

Haemophilus influenzae

Neisseria meningitidis

Streptococcus pneumoniae

Listeria monocytogenes mening. occur in extreme ages of life or in AIDS patients, in

pregnant women is associated with risk of miscarriage)

Streptococcus agalactiae colonizes the vaginal and gastrointestinal tract

Staphylococcus aureus and epidermidis

Enterococcus ssp

Propionibacterium acnes

Escherichia coli

Klebsiella pneumoniae

Pseudomonas aeruginosa

Salmonella ssp account for 1% of cases of meningitis in infant and neonates (high mortal.)

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Acute meningitis: other bacterial agents of aseptic meningitis

Rickettsiae (obligated parasites)

Rickettsia rickettsii zoonotic infection endemic in mediterranean countries

3% of cases develops meningitis

Rickettsia conorii zoonosis, humans may be infected by a puncture of ticks

Rickettsia prowazekii trasmetted by pediculi

Spirochetes

Treponema pallidum syphilis agent, meningitis occurs in the first years of infection

Borrelia burgdorferi (Lyme disease) transmissed by infected ticks.

Meningitis occurs in 10-15% of cases

Leptospira ssp zoonotic infection, may be asymptomatic or severe ranging from low

grade fever to meningitis. Diagnosis is performed by serology

Protozoa and Helminths

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Community-acquired meningitis

Bacterial meningitis one of the most important disease in worldwide is

considered.

Haemophilus influenzae, Neisseria meningitidis and Streptococcus

pneumoniae, (the tree most common etiological agents) account for more

than 80% of cases.

Surveillance studies conducted during 1995, showed the incidence of bacterial

meningitis decreased. This decrease was a result of vaccination against

Haemophilus influenzae type B (recommended for pediatric use).

Bacterial meningitis is now a disease of adults rather than of infants or

children.

In patients 16 years old or older, community-acquired bacterial meningitis is

caused by S. pneunomiae, N. meningitidis and Listeria monocytogenes

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Bacterial meningitis in hospitalized patients

Bacterial meningitis is also a significant problem in hospitalized patients with

most cases (40%) caused by Gram-negative bacilli (death level about 35%).

The mortality rate for meningitis caused by Enterobacteriaceae is 80%.

More than half of cases in children younger than 24 mounths is caused by

Salmonella, an unusual meningeal pathogen in industrial countries.

In addition bacterial meningitis is a major problem in underdeveloped countries

with 50% of deaths occurring within 48 hours of hospitalization

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Bacterial agents of meningitis: Haemophilus influenzae

Most cases of meningitis caused by Haemophilus influenzae occur in infants

and children younger than 6 years (incidence peak of 6 to 12 mounths), with

90% of cases caused by capsular type B strains.

A significant reduction has been seen in incidence of invasive infection including

bacterial meningitis caused by H. influenzae type B in Europe and in United

States.

This decrease is attributed to use of conjugate vaccine (routine use in children beginning at 2 mounths of age). The number

of cases has decreased more than 90%.

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Bacterial agents of meningitis: Neisseria meningitidis

Neisseria meningitidis causis meningitis in children and young adults.

Meningococci of serotypes B, C, Y account for most of epidemic diseases.

Serogroup B is frequent in Italy, it accounts for 75% of cases.

Respiratory tract infections, with viruses, such as influenza virus, may play a

role in the pathogenesis of invasive meningocaccal disease.

Patients with deficiencies in the terminal complement components have an

increased incidence of neisserial infection.

An increased risk of invasive meningococcal disease has been observed in

subjects with properdin deficiencies, which suggests a potential role of the

alternative pathway in a complement mediate resistance against meningococci.

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Bacterial agents of meningitis: Neisseria meningitidis

In conclusion because

meningococcal meningitis occurs in approximately 39% of persons with complement deficiencies, a screening test for

complement function should be performed for all patients with invasive meningococcal infection.

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Bacterial agents of meningitis: Streptococcus pneumoniae

Streptococcus pneumoniae is one of the most frequently observed etiologic

agent of bacterial meningitis, it accounts for about 45% of cases.

Streptococci may be divided into more than 90 serotypes, but only 18 are

responsible for 82% of the cases of pneumococcal pneumonia, with a frank

correlation between bacteremic serotypes and those implicated in meningitis.

Meningitidis can derive by cases of pneumonia, otitis media, mastoiditis,

sinusitis ,endocarditis.

Serious infections may be observed in patients affected by:

alcoholism, malnutrition, chronic liver or renal disease, diabetes, multiple

myeloma etc.

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Bacterial agents of meningitis: Streptococcus pneumoniae

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Bacterial agents of meningitis: Listeria monocytogenes

Listeria monocytogenes causes 8% of cases of bacterial meningitis, has been isolated fromland, water, vegetable (infection is often associated with the ingestion of contamined foods)Listerial infection is most common in infants, in adults older than 60 years,alcoholics, cancer patients, receiving corticosteroid therapy and immunosuppressed adults.Pregnant women may present the organism asymptomatically in their genital tract and they transmit the infection to newnates.

GBNA medium (Gum base nalidixic acid) green-blue colonies

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Bacterial agents of meningitis: Streptococcus agalactiae

Group B Streptococcus

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Bacterial agents of meningitis: Streptococcus agalactiae

Group B Streptococcus, called Streptococcus agalactiae, is a common cause

of meningitis in neonates (52% of all cases), it has been isolated from the

vaginal or rectal cultures of asymptomatic pregnant women.

The risk of trasmission from mother to infant increases on the basis of inoculum

of organisms and on the basis of the number of maternal colonization sites.

Horizontal trasmission has also been documented from the hands of nursery

personnel in hospital.

Group B Streptococcus can also cause meningitis in adults especially in

case of diabetes, cardiac disease, renal failure, corticosteroid therapy.

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Bacterial agents of meningitis:aerobic Gram-negative bacilli

Aerobic Gram-negative bacilli such as Klebsiella ssp, Escherichia coli, Serratia

marcescens, Pseudomonas aeruginosa, Salmonella ssp. are important etiologic

agents of bacterial meningitis. These agents may be isolated from the CSF of

patients after head trauma or neurosurgical procedures and may also be found

in neonates, older adults, immunocompromized patients.

In patients affected by E.coli meningitis, 75% of cases are caused by strains

with K1 antigen. Almost half of pregnant women have this organism

isolated on rectal culture (75% of their infants will be colonized during the first

days of life).

Horizontal trasmission from nursery staff members has also been reported.

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Viral meningitis

Enteroviruses are the most important viruses causing meningitis.

Because they are able to escape host defence mechanisms, they may replicate

and disseminate with CNS invasion.

The clinical manifestation of enteroviral meningitis depend on host age and

immune status. In neonates, fever is always present and is accompanied

by any combination of vomiting anorexia, rush and upper respiratory symptoms

and signs.

Nuchal rigidity is present in more than half of patients, expecially in children

in adulescents and in adults.

Photophobia is present in older patients.

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Bacterial meningitis: symptoms andsigns

• Patients with bacterial meningitis present fever headache, meningismus (nuchal rigidity and positivity to Kernig and Brudzinshi signs), accompained by

signs of cerebral dysfunction ranging from lethargy to coma.• In case of bacterial meningitis in adults the classic triad: fever, nuchal rigidity

and change in mental status was found in two third of patients.

• Some categories of patients may not manifest many of the classic signs of

bacterial meningitis

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Diagnosis of bacterial meningitis

For the diagnosis of bacterial meningitis, CSF collected by

lumbar puncture, may be tested.

Typical findings in acute bacterial meningitis are observed:

Opening pressure 200-500 mm H2O

White blood cell count 1000-5000 mm3

Percentage of neutrophils > 80%

Protein 100-500 mg/dL

Glucose <40 mg/dL

Gram stain positive 90%

Culture positive 85%

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Antimicrobial therapy of acute meningitis

Microorganism Standard therapy Alternative therapies

Haemophilus infl.

β lactamase neg. Ampicillin Third gen ceph, cefepime, chloramph.

β lactamase pos. Third gen cephalosporins Cefep, chloramph. Fluoroq.

Neisseria meningPenicillin MIC<0,1 Penicillin G, ampicillin Third gen ceph, chloramph.

Penicillin MIC>2 Vancomycin, third gen. cephalosporins

Third gen ceph, chloramph.

fluoroquinolones

Streptococcus pneumoniaePenicillin MIC<0,1 Penicillin G, ampicillin Vancomycin, third gen.

cephalosporins

Penicillin MIC>2 Vancomycin, third gen. cephalosporins

third gen. Cephalosporins plus fluoroquinolones

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Antimicrobial therapy for acute meningitis

Microorganism Standard therapy Alternative therapies

Enterobacteriacee Third gen. cephalosporins Aztreonam, fluoroquinolones, meropenem

Pseudomonas aerug. Ceftazidime or cefepime Aztreonam, fluoroquinolones, meropenem

Listeria monocytogen Ampicillin or penicillin G Trimethoprim sulpham.

Streptococcus agalac Ampicillin or penicillin G Third gen. Cephalosporins, vancomycin

Staphylococcus aur.

Methicillin sensitive oxacillin vancomycin

Methicillin resistant vancomycin vancomycin

Staphylococcus epid vancomycin

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Immunoprophylaxis: Haemophilus influenzae (recommended vaccination)

Vaccination to prevent infection is a vary useful measure for

decreasing the incidence of bacterial meningitis.

For Haemophilus influenzae type B, the availability of conjugate

vaccines has decreased the number of cases more than 90% in

recent years (conjugate vaccines are effective in reducing

nasopharyngeal colonization).

Three different types of vaccines are licensed for immunization

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Immunoprophylaxis: Haemophilus influenzae (recommended vaccination)

The Hib vaccine is available as:

Hib (alone)

Hib in combination with DTaP (Diphtheria-Tetanus-acellular

Pertussis) vaccine

Hib in combination with recombinant hepatitis B (HBV) vaccine

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Immunoprophylaxis: Neisseria meningitis

Monovalent vaccines using purified serogroup capsular polysaccharides

antigens of Neisseria meningitis have been shown to be immunogenic in

humans.

Serogroup A and C vaccines have demonstrated clinical efficacies of

approximately 85 to 100% in older children and adults (serogroup C component

is poorly immunogenic in recipient younger than 2 years).

The efficacy decreases durung the first 3 years after a single dose.

Vaccination with the quadrivalent meningococcal vaccine (A, C, Y, W135)

is recommended for high risk patients.

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Immunoprophylaxis:Streptococcus pneumoniae

Use of current 23-valent pneumococcal vaccine is recommended for prevention

of bacteremic pneumococcal disease in high risk persons 65 years and older,

with chronic cardiovascular disease, chronic pulmonary disease, diabetes

mellitus, alcoholism, chronic liver disease etc.

Heptavalent conjugate pneumococcal vaccine, administared in four doses

(2, 4, 6, 12 months) is used in children and in infants (efficacy 97%) in

prevention of invasive pneumococcal disease.

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Special problems: nosocomial infections

Nosocomial infections in hospitalization period occur and are a result of

treatmen in hospital or in healthcare service units.

Infections are considered nosocomial if they appear 48 hours or more after

hospital admission or within 30 days after dismission.

Nosocomial infections are known a hospital-acquired infections or

healthcare-associated infection.

Nosocomial infections can cause severe pneumonia, infections of the

urinary tract, bloodstream etc. Many types of infections are difficult to

treat with antibiotics and antibiotic resistance is vary frequent.

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Nosocomial infections control

Nosocomial infection control is a discipline developed during the late 1950 to

prevent the problem of nosocomial staphylococcal infections.

The primary role of an infection-control program is to reduce the risk of

hospital-acquired infection transmitted by patients, students and visitors.

The hospital infection control program vary from institution to institution, but,

generally, regards the following areas:

Surveillance

Education

Antimicrobial utilization

Environmental Hygiene

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Nosocomial infections

SurveillanceSurveillance for nosocomial infections is generally reserved to areas of the

hospital where the highest rates of infection, highest impact of infection and

antibiotic resistance are likely to be found.

These areas include: intensive care units, cardiothoracic surgery units,

hematology and oncology units.

The importance of surveillance was demonstrated by the reduction in

nosocomial infections in hospitals with active surveillance program, compared

with hospitals without such programs.

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Nosocomial infections

EducationA fundamental role in prevention of nosocomial infections is to educate

the hospital staff in specific sections for the control of diseases: sterilization,

disinfection and infection-control policies.

In many hospitals the epidemiology team is responsible for blood-borne

pathogen training and for airborne-isolation-mask training and fit testing.

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Nosocomial infections

Antimicrobial utilizationAboud one-half of hospitalized patients receive antimicrobial agents and their

use varies widely in hospitals.

The hospital epidemiology program should monitor the antimicrobial susceptibi-

lity profiles to observe the development of antimicrobial resistance.

The results should be correlated with the antimicrobial agents currently used in

the institution.

Many remedies should be made to optimize antimicrobial prophylaxis for

surgical procedures, optimize the choice of empiric antimicrobial therapy and

improve the antimicrobial prescribing practices

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Nosocomial infections

Environmental hygiene

Because most of hospitalized patients has become immunocompromized,

the importance of environmental hygiene has significantly increased.

The control and prevention of environmental infection by hospital

epidemiologists must be considered.

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Disinfection, sterilization and control of hospital environment

A major risk of clinical procedures is the introduction of infections. A failure of

disinfection or sterilization techniques increases not only the risk of person-to-

person trasmission (e.g, hepatitis B virus), but also the risk of environmental

pathogens trasmission (e.g. Pseudomonas aeruginosa, Klebsiella pneumoniae).

The use of disinfectants, the sterilization of medical or surgical instruments is

crucial to inhibit the transmission of infectious pathogens to patients.

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Disinfection, sterilization and control of hospital environment: definition of terms

Sterilization:

is a complete suppression or destruction of all forms of microbial

life. Steam under pressure, dry heat, ethylene oxide gas, and liquid chemicals

are the principal sterilizing agents used.

Disinfection:

describes a process that eliminates many or all pathogenic microorga-

nisms with the exception of bacterial spores. The efficacy of disinfection

depends on the level of bacterial contamination, on the nature of objects, on the

presence of biofilms, on the temperature and pH.

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Disinfection, sterilization and control of hospital environment: definition of terms

Disinfection differs from sterilization by the absence of sporicidal property, but

this is an oversimplification. Many disinfectants in fact can kill spores with

prolonged exposure times.

Cleaning

is the removal of visible organic and inorganic materials from objects and

surfaces, using water with detergents or enzymatic products.

Decontamination

is a procedure that removes pathogenic microorganisms from objects.

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Disinfection: chemical disinfectants

Alcohol in the health care setting,

“alcohol” indicates two water-soluble chemical compounds: ethyl alcohol and isopropyl alcohol. These alcohol are rapidly bactericidal rather than bacteriostatic against vegetative forms of bacteria, they are also tuberculocidal, fungicidal, virucidal, but do not kill bacterial spores.

Alcohols are not recommended to sterilize medical and surgical materials for the absence of sporicidal action and inability to penetrate protein-rich materials.

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Disinfection: chemical disinfectants

Chlorine and chlorine compounds

Hypochlorites are the most widely used of the chlorine disinfectants and are available in a liquid or solid form. They

have a broad spectrum of antimicrobial activity (bactericidal, virucidal, fungicidal, sporicidal, mycobactericidal). Remove dried or fixed organisms and biofilm from surfaces, with a low incidence of serious toxicity.

In hospital are used as irrigating agents in endodontic treatment, todisinfect laundry, dental appliances and water distribution system inhemodialysis centers and hemodialysis machines.

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Disinfection: chemical disinfectants

Hydrogen peroxideMany reports describe bactericidal, virucidal, sporicidal and fungicidal

propertiesof hydrogen peroxide, in hospital it has been instilled into urinary drainage bagsto eliminate a source of bladder bacteriuria and environmental contamination.(this procedure did not reduce catheter associated bacteriuria).

One of the more recent low-temperature plasma sterilizers is STERRAD system.It uses hydrogen peroxide vapor and low-temperature gas plasma to sterilize most clinical devices (hydrogen peroxidein presence of electric circuit is transformed in plasma state with production of free radicals).

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Disinfection: chemical disinfectants

IodophorsIodophors are used for the disinfection of blood-culture bottles and medical

instruments (endoscopes, hydrotherapy tanks).

Antiseptic iodophors are not used such as hard-surface disinfectants.

Iodine or iodine-based antiseptic should not be used on silicone catheters

because the silicone tubes may be damaged.

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Disinfection: chemical disinfectants

Quaternary ammonium compoundsThe quaternary ammonium compounds are widely used as surface disinfectants.

There have been some reports of infections related to contaminated

quaternary ammonium compounds used to disinfect materials such as

cystoscopes or cardiac catheters (most Gram-negative enterobacteria have

been found to survive or grow in them)

The quaternaries are commonly used in enviromental disinfection of non critical

surfaces such as floors, forniture and walls

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Disinfection against emerging pathogens

Revelant emerging pathogens include: Cryptosporidium parvum

(causes oppurtunistic infections in AIDS patients), Helicobacter pylori (gastritis

and ulcer), E. coli 0157:H7 (is enterohemorrhagic E. coli), HIV, Hepatitis C

virus, Creutzfeld-Jakob prion (causis spongiform encephalopathy), antibiotic-

resistant bacteria such as MRSA (methicillin-resistant Staphylococcus aureus),

multidrug-resistant Mycobacterium tuberculosis and nontuberculosis

mycobacteria.

The susceptibility of each of these pathogens to chemical disinfectants has been

studied. With the exception of prion (see later) standard disinfection procedures

are able to sterilize or disinfect instruments or medical devices

contaminated with blood or other organic fluids from infected persons.

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Disinfection against prions

The prions of Creutzfeldt-Jakob disease exhibit an unusuals resistance to

conventional chemical and physical methods.

For high-risk tissues (brain, spinal cord etc), high risk patients and critical

medical devices, is recommended to clean the device and sterilize by one of

four methods.

1) Immerse in 1N NaOH for 1 hour, remove and rinse in water and autoclave

at 121° C for 1 hour.

2) Immerse instruments in 1N NaOH for 1 hour and heat in a gravity

displacement sterilizer at 121° C for 30 min.

3) Autoclave at 134°C for 18 min. in a prevacuum sterilizer.

4) Autoclave at 132°C for 1 hour in a gravity displacement sterilizer.

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Infections caused by percutaneous intravascular devices

The use of intravascular devices, to deliver sterile fluids, drugs and nutritional

products has increased during the past decades. It is estimated that aboud 50%

of ospitalized patients receive intravenuos therapy with a large risk for local and

systemic blood stream infections.

The use of therapeutic medical devices is often associated with complications.

Vascular catheters have become an increasingly source of bacteremias (from

3% in the mid-1970s to 19% in the early 1990s)

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Nosocomial bacteremia caused by percutaneous intravascular devices

Pathogenesis: In order of intravascular device-related bacteremia, microrganisms must gain

access to the extraluminal or intraluminal surface of the device. Microbial

adherence and incorporation into biofilms then occurs, resulting first in infection and then in hemotogenous dissemination.

The figure illustrates the potential points of access to an intravascular device, each of which is associated with cases of nosocomial bacteremia

health care worker

health

Device-related bacteremia can derive by:

1) point of insertion of device2) contamination of the device or attachment of pathogens on the skin surrounding the insertion site

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Nosocomial bacteremia caused by percutaneous intravascular devices:

other infection sources

Contamination may occur in case of defects in container

Contamination may occur in case of malfuntioning air filter

Contamination may occur in case of defect of pressure measuring devices

Contamination may reach blood stream at the catheter insertion size

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Nosocomial bacteremia caused by percutaneous intravascular devices: Microbiology

Staphylococci predominate, and are the most frequently isolated pathogens in

device-related infections.

Although Staphylococcus aureus is a frequent cause of device-associated

infections, the coagulase-negative staphylococci have become the most

common causes of these infections in the past two decades, especially in

immunocompromizes patients and when long-term central venous access is

required.

Recent studies have suggested that CN staphylococci may be able to adhere

to plastic catheters more than other microrganisms (ability to biofilm formation).

Staphylococci account for two thirds to 90% of the cases of bacteremia

associated with medical implanted devices.

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Microbiology of device-associated Bacteremia: (other microrganisms)

Coagulase-negative staphylococci including Staphylococcus epidermidis

Staphylococcus aureus

Enterococcus ssp

Serratia marcescens

Candida albicans

Candida tropicalis

Pseudomonas aeruginosa

Klebsiella ssp

Enterobacter ssp

Citrobacter freundii

Corynebacterium ssp

Burkholderia cepacia complex

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Microbiology of device-associated Bacteremia: (other microrganisms)

Recent studies have suggested an increase in catheter-associated infections

caused by Gram-negative bacilli.

The frequent etiology of unusual microrganisms such as: Enterobacter,

Burkholderia, Citrobacter, suggests the possible presence of these

pathogens in hospital environment.

Concomitant use of broad-spectrum antimicrobials expecially in

immunocompromized patients, contributes to increase the number of device-

associated bloodstream infections produced by a variety of unusual bacterial

and fungal pathogens.

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Antibiotic lock prophylaxis

The use of antibiotic lock solution, in which an antibiotic is injected into the catheter lumenand the solution is left within the lumen for periods of some hours or days has received attention in the past years. Antibiotic lock therapy in combination with systemic antibiotic isrecommended for prevention of bacteremias related to central venous catheters or implantable devices, when the catheters are not removed and the infection is due to coagulase-negative staphylococci, S. aureus or Gram-negative bacilli producing biofilm.

Antibiotic lock solution containstaurolidine, biocompatible antibiotic,citrate and anticoagulant agent

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Nosocomial respiratory infections

Nosocomial respiratory tract infections are an important cause of mortality and

morbility in world and they account for approximately 15% of all

nosocomial infections.

Generally any respiratory infection, in health care setting, may occur but the

adjective “nosocomial” indicates those acquired within hospitals.

Many viruses such as: Influenza virus, respiratory syncytial virus and

parainfluenza virus can infect hospitalized patients.

Aspergillus ssp, herpes virus and other opportunistic pathogens cause

respiratory tract infections in transplant recipients and other

immunocompromized patients.

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Nosocomial pneumonia

Pneumonia is a frequent, severe and costly problem in hospitalized patients.

It accounts for 15% to 20% of nosocomial infections and is second only to

urinary tract infection.

In intensive care units, pneumonia is the number one of nosocomial infections.

Hospital acquired pneumonias account for the majority of deaths

attributed to nosocomial infections

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Nosocomial pneumonia

Definition

Nosocomial pneumonias are inflammatory conditions

of the lung parenchyma caused by infectious agents

not present or incubating at the time of admission,

developed 48 to 72 hours after admission to the

hospital.

Accumulation of neutrophils in the distal bronchioles,

alveoli and interstitium of the lung constitutes the

histopathologic report.

In the last decade, definitions that include

positive cultural results have become preferred by

clinical investigators.

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Nosocomial pneumonia:risk factors

A number of studies performed during the last years have established a numberof risk factors for nosocomial pneumonia, such as the elderly age.These subjects show wide compromises in respiratory tract functions, resulting in respiratory tract obstruction, reduction of the lung volumes, decreased filtration ofinspired air, or decreased clearance of secretion. Sometimes this condition isassociated with other intrinsicneurologic defects.

Insertion of an endotracheal tube allows the direct access of microrganisms to the lower respiratory tract.

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Nosocomial pneumonia:etiology

When disease develops within 4 or 5 days of admission or intubation, the

most common etiological agents associated with hospital-acquired

pneumonia are: Haemophilus influenzae, Streptococcus pneumoniae and

Moraxella catarrhalis.

These bacteria probably originate from the oropharyngeal flora present at

admission.

When disease develops after 5 days a large number of pathogens

may be associated with nosocomial pneumonia.

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Etiology of nosocomial pneumonia after 5 days of admission

Staphylococcus aureus

Streptococcus pneumoniae

Haemophilus ssp (predominantly H. influenzae)

Moraxella catarrhalis

enterobacteriaceae

Pseudomonas ssp (predominantly P.aeruginosa)

Acinetobacter ssp

Other enteric Gram negative bacilli

Fungi (predominantly Candida ssp)

Mixed bacteria: coagulase neg Staphylococci, enterococci, viridans streptococci, Neisseria, anaerobes

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Examples of antimicrobial agents recommended for empirical therapy of nosocomial pneumonia

Microorganisms Clinical setting antibiotics

S. aureus

S. pneumoniae

H. influenzae

enterobacteriaceae

Severe disease before 5 days in absence of risk factors

or

Moderate disease in absence of risk factors

Cefotaxime or ceftriaxone or

Piperacillin/tazobactam or

Clindamycin and ciprofloxacin or

Vancomycin or levofloxacin

P. aeruginosa

Acinetobacter ssp

Stenotrophomonas maltophilia

Burkholderia cepacia

MRSA

Severe disease in presence of risk factors

or

Moderate disease in presence of risk factors

Gentamicin or ciprofloxacin plus

Imipenem/cilastatin or meropenem or piperacillin/tazobactam or

Cefepime or cefotaxime and vancomycin or linezolid (if MRSA

likely)

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Nosocomial urinary tract infections

Urinary tract infection (UTI), is the most common nosocomial infection that

occurs in both hospitals and nursing homes.

In hospitals where the epidemiology has been better investigated, 80% or more

nosocomial UTIs are related to the use of urethral catheters. Another 5% to

10% occur after other genitourinary manipolations.

In this period the widespread use of systemic antibiotics determines an

increasing number of Candida ssp isolated from catheterized urinary tract.

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Risk factors for UTIs associated with catheterization

Many studies have described the risk factors for catheter-associated urinary

tract infections.

Time of catheterization

Microbial colonization of the drainage bag

Diabetes mellitus

Absence of antibiotic use

Female sex

Abnormal serum creatinine

Errors in catheter care

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Time of catheterization

The time of catheterization is the most important risk factor for the

development of catheter-associated infections.

catheterization is required in these cases:

Surgery (1 to 7 days)

Urine measurement (serious ill patients 7 to 30 days)

Urine retention (1 to more than 30 days)

Urinary incontinence (more than 30 days)

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Short-Term Catheterization

Short-term catheterization is vary used in hospital, in fact 15-25% of hospitalized

patients receive a catheter.

Most catheters are applied only for a short time.

Nevertheless, between 10% and 30% of these catheterized patients develop

urinary tract infection.

In short-term catheterized patients, Escherichia coli is the species most

frequently isolated.

Other common organisms are Pseudomonas aeruginosa, Klebsiella

pneumoniae, Proteus mirabilis, Staphylococcus epidermidis, enterococci

and Candida ssp.

Most episodes of bacteriuria in short-time catheterization are caused by a single

organisms.

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Long-term catheterization

Urines of long-term catheterized patients become infected.

Two different situation can occur.

The incidence of new episodes of UTIs similar to those observed in

short-time catheterized patients (including a wider variety of Gram positive

and Gram negative species.

The ability of some microbes to persist for weeks or months in the

catheterized urinary tract

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Long-term catheterization: microbiology

Two particular types of microorganisms infect the long-term catheterized urinary

tract:

E. coli (strains with specific type 1 pilus) Providencia stuartii (strains with specific MR/K adhesin)

P. stuartii strains are rarely found outside the catheterized urinary tract

(it uses catheter such as a niche). It causes purple urine bag syndrome

Urine specimens for long-term catheterized patients, show polymicrobial

bacteriuria in more than 95% of cases

Bacteriuria include common uropathogens such as E.coli, Pseudomonas

aeruginosa and Proteus mirabilis

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Complications associated with long-term catheterization

The most common complications are:

Fever (low-grade)

Catheter obstructions (caused by bacteria or glycocalix compounds)

Urinary stones (P. mirabilis produce urease, which hydrolyzes urea

to ammonia, increasing urine pH and causing crystal-

lization in catheter lumen).

Chronic renal inflammation common in long-term catheterized persons.

Often chronic pyelonephritis associated

with deformed calices can occur.

Other complications urethritis, epididymitis, scrotal abscess etc

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Treatment

Asyntomatic catheter-associated bacteriuria should not be treated.

In case of syntomatic bacteriuria, patients generally are treated with the same

antibiotic therapy used to treat bacteriuria from a known or suspected

bacterial species.

Antibiotics should be modified in case of different report by clinical microbiology

laboratory

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Surgical and trauma-related wound infections

Wound infections after surgical procedures may be frequent in hospitals.

The prognosis of surgical and trauma related infections, depend on

the interaction between:

Patients-related factors such as host immunity, nutritional status, presence of

chronic diseases

Procedure-related factors severity of trauma

Microbial factors adherence and invasion of implicated microrganisms

Perioperative antimicrobial prophylaxis

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Microbiology of wound infections

Bacterial contamination of the surgical wounds is inevitable.

Despite many techniques have been performed to eliminate this risk,

bacteria can be isolated from wound surface after surgical procedure.

Numerous species have been described as wound pathogens:

Staphylococcus aureus, CN staphylococci, Enterococci, Escherichia coli,

Pseudomonas aeruginosa, Enterobacter, Proteus mirabilis, Klebsiella

pneumoniae, Bacteroides fragilis.

Unusual and hard-to-culture species including: non-tuberculous mycobacteria,

Nocardia species, Legionella species, Mycoplasma hominis etc. are

occasionally implicated.

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Source of contamination of surgical wound

Despite numerous sources of bacterial contamination of surgical wound have

been described, two are the most common the source of contamination.

The direct contamination of a patient’s endogenous flora at the moment of

surgery, the most common mechanisms is considered.

Trasmission from contaminated surgical instruments or surgical materials,

contamination from the skin, mucous membranes of operating room staff

have been implicated as potential sources of microbial contamination.

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Perioperative antibiotic therapy

Over the past 20 years, the efficacy of antimicrobial prophylaxis in surgical

procedures has been documented.

The interaction between inoculated bacteria and prophylactically

administared antibiotic, is one of the most important determinant for the

positive prognosis of infected wound in surgical procedures.

For example, without antibiotic prophylaxis the referred risk in developing a

Staphylococcus aureus wound infection after cardiac surgery is 15% to 45%

(approximately the frequency of naso-pharingeal colonization).

The success of perioperative prophylaxis correlates directly with the

susceptibility of bacteria to antibiotics