NEWER ANTIBIOTICS

NEWER ANTIBIOTICS

B-LACTAMS QUINOLONESCEPHALOSPORINS LEVOFLOXACIN

SPARFLOXACINCEFDITOREN GATIFLOXACINCEFEPIME GREPOFLOXACIN CEFEPIROME TRAVOFLOXACIN

CARBAPENEMS MOXIFLOXACINERTAPENEM CLINAFLOXACIN

MACROLIDES OXAZOLIDINONESDIRITHRMYCIN LINEZOLID

STREPTOGRAMINSJOSAMYCIN DALFOPRISTIN

AMINOGLYCOSIDES QUINPRISTIN

ARBIKACIN GLYCO/LIPOPEPTIDESDAPTOMYCINORITAVANICIN

GLYCINCYCLINS TEGICYCLINS

CEPHALOSPORINS• The activity of cephalosporins increases over gram negative organisms

as the generation passes• 4th generation are even resistant to b-lactamases and highely active

against pseudomonas• They act by inhibiting cell wall synthesis• INDICATION DOSAGE :cefditoren at 200-400mg po12hly indicated

for bronchitis, complicated sinusitis,otitis media,uti cefepime at 500-2g iv 8-12hly indicated for empirical therapy in febrile neutropenic patients and ABR gram-ve bacteremia

• ADVERSE EFFECTS:git effects, thrombophlebitis(cfepime), rare ones like hypersensitivity,interstitial nephritis,anemia, leukopenia

• CONTRAINDICATIONS: Decreased dosage in renal failure .cefepirome contra in pregnancy lactating .cefepime is to used with caution in lactating patients

QUINOLONES

• The activity of quinolones increases over gram +ve organisms as the generation increases .4th generation drugs are active against even anaerobic organisms

• INDICATIONS: levofloxacin(250-750mg po od)for sinusitis, bronchitis, pneumonia, uti . Gatifloxacin(400mg po/iv od 7-14days) for LRTI,UTI, gonorrhea .moxifloxacin(400mg po/iv od) for sinusitis,bronchitis ,pneumonia

• ADVERSE EFFECTS :most well tolerated drugs .nasuea ,rashes, cns disturbances .

• INTERACTIONS: increases QT interval• CONTRAINDICATIONS:2nd,3rd generation decrease dosage in renal

failure .4th generation decrease dosage in hepatic failure • Not to used in pregnancy lactating children below 18yrs

GLYCINCYCLINS(TEGICYCLIN)

• Bacteriostatic drug having good activity against gram+ve and gram –ve organisms

• Activity similar to tetracyclins• Inhibits protein synthesis by binding with 30s subunit• INDICATION: complicated skin&intra abdominal infections caused

by susceptable strains• DOSAGE:100mg stat followed by 50mg every 12th hly IV for 5-14days• ADVERSE EFFECTS: git side effects, irritation at injection site

,photosensitivity• INTERACTIONS: decreased elimination of warfarin• CONTRAINDICATIONS: not safe in pregnant lactating and children

below 8 yrs

KETOLIDE(TELITHROMYCIN)

• Telithromycin has broad spectrum of activity against gram +ve bacteria ,active against most macrolide resistant pneumococci, but like erythromycin not active against staph aureus

• INDICATION: for sinusitis, bronchitis , pneumonia• DOSAGE:800mg od daily dosage• ADVERSE EFFECTS: git side effects , vision problems ,

hepatotoxicity, pseudomembrane colitis • INTERACTIONS: inhibitor of cyp3a4• CONTRAINDICATIONS: decreased dosage in hepatic failure, no data

for pregnant, lactating, children

OXAZOLIDINONES(LINEZOLID)

• Outstanding activity against variety of gram positive organisms • Linezolid prevents formation of the 70S ribosome complex• No cross resistance• INDICAT/DOSAGE: at 10mg/kg iv/po for 10-14days is used as

an alternative to vancomycin for MRSA pneumonia/enterococcal meningitis

• Adverse effects: git side effects /oral moniliasis/ taste perverstion thrombocytopenia / myelosupression

• Contraindications: pregnancy/lactation-caution .FDA has approved for treating infections in infants .NO contraindication in renal, hepatic failure

• Interactions: MAO inhibitor

STREPTOGRAMINS(DALFOPRISTIN-QUINPRISTIN)

• Good activity against MDR gram +ve organisms except enterococcal feacalis active against gram –ve URT pathogens

• Inhibits protein synthesis by binding to 50s ribosome • Both are static drugs individually but cidal when used in combination,• StreA:streB—30%:70%• INDICATION: VRSA ORSA VR enterococcal feacium infections• DOSAGE: 7.5mg/kg IV ever 8-12hly for 7das• ADVERSE EFECTS: thrombophlebitis, arthralgias ,myalgias • INTERACTIONS: inhibits cyt p3a4• CONTRAINDICATIONS: hepatic failure , not safe in children

pregnant ,lactating women

GLYCO/LIPOPEPTIDE(DAPTOMCIN)

• Bactericidal activity against wide variety of gran +ve bacteria including enterococi,staphylococci,streptococci that are even resistent to methicillin& vancomycin

• Daptomycin bind to bacterial mambrane causes rapid depolarisation of membrane potential resulting in inhibition of dna rna protein synthesis

• INDICATION: at dose of 4mg/kg iv od is approved for treatment of complicated skin infections

• ADVERSE EFFECTS: git side effects , increased LFTS ,increased CPK with or with out myopathy

• CONTRAINDICATIONS: renal failure ,inpregnant and lactitating no data

CARBAPENEMS(ERTAPENEM)

• Effective against gram –ve bacteria and anaerobic bacteria • It inhibits cell wall synthesis• INDICATION: indicated only for community acquired

infections because of its lack activity against pseudomonas• DOSAGE:1gm iv once aday• ADVERS EFFECTS: diarrhoea• seizeures(older,renal failure,cns

pathology)• pseudomembrane colitis• CONTRAINDICATIONS: renal failure, no data in

pregnant lactating and children

Why?

•Increasing resistance patterns among both community and hospital acquire infections•Judicious use will prevent resistance strains to emerge

INDICATIONS

1.Clinical scenario

2.Organisms common in that scenario

3.Antibiotic resistance patterns

4.Pharmacokinetics of the drug

5.Clinical trials

Community infections

•Pneumonia

•Meningitis

•Osteomyelitis

COMMUNITY ACQUIRED PNEUMONIA

Core pathogens

•Streptococcus pneumonia•Mycoplasma pneumoniae (during epidemics)•Haemophilus influenzae•Staphylococcus aureus•Chlamydia pneumonia•Legionella pneumophila

Pencillin resistance is a major problem in these casesSo the drug used should take into account of the organism, risk factors for atypical organisms,anti biotic resistance

With no risk factors

• Patient can be treated with

• Ketolides(telithromycin)

• New extended spectrum fluroquinolones

• Ertapenem if there is e/o of vancomycin resistance

Fluoro quinolene should not be used in patients with Rhinitis,sinusitis,Pahryngitis unless there is evidence of pneumonia……………ACP recommendation.

Meningitis

Mc organisms

• Strep.pneumoniae• H.influenza• Neisseria meningitidis• Streptococcus agalactiae• Listeria monocytogenes

Pencillin resistance is also major problem

So empirical therapy is started with 3rd generation cephalosporinsBut if risk factors are present for listeria ampicillin with gantamycin should be used as empirical therapy

Cephalosporins are ineffective

AFTER GRAM STAIN AND CULTURE

EMPIRICAL THERAPY CAN BE CHANGED TO

MORE SPECIFIC THERAPY

In adults penetration of vancomycin is not good especially if dexamethasone is being used So in such cases ceftriaxone plus rifampcin is used

Newer antibiotic LINEZOLIDE irrespective of dexamethasone therapy reaches high concenteration in CSF fluid so can be used in stead of ceftriaxone +rifampcin

Osteomyleitis

Acute haematogenous infection : Staph.aureus

Secondary to contagious focus of infectionPolymicrobial: staphylococci, streptococci, enteric organisms, and anaerobic bacteria.

P. aeruginosa is frequently associated with puncture wounds of the foot (especially by a nail through a sneaker)

Penicillin-resistant, methicillin-sensitive (MSSA ) --- ceftriaxone, 1 g IV q24h

Methicillin-resistant (MRSA ) --- Vancomycin

Vancomycin alone always not effective in such cases. Rifampcin can be added New antibiotics like daptomycin is effective

osteomyelitis due to Enterobacteriaceae ---- Extended spectrum β-lactam antibiotics fluoroquinolone

Hospital acquired infections

Most common are

•UTI

•Pneumonia

•Surgical site infections

UTI

Mc organisms are E.coli, enterobacteraceaenterococcipseudomonas

Risk factors for uti include catheterization,instrumentation,diabetesMost are resistant to tmp-smx,amoxiciliinIn such cases

Fluroquinolones,extende spectrum b-lactams likeTicarcillinCarbapenem—(Imipenem)

Fosfomycin has been recently approved for uncomplicated UTI

Hospital acquired pneumonia

Most common organisms are ;•Pneumococcus•Staph areus•Enterobacteriacea•Pseudomonas•Anaerobes

Many are resistant to pencillin,Enterobacteriacea are resistant to cephalosporinsPseudomonas to cephalosporins,pencillin

HAP is classified into 3 types based on risk factors and severity of pneumoniaAnd the time of development of pneumonia(<5days >5days)

1.Moderate to MILD ,early onset, no risk factors treated like CAPRx: 3rd generation cephalosporins or fluroquinolones

2.Moderate to severe,early onset, if risk factor presentadditional antibiotic is added

If risk factors …

Anaerobes…… Clindamycin

Pseudomonas Extended spectrum Blactam+aminoglycoside

Staph.aureus Vancomycin,linezolid,ortitavanicin

Entero bacteriacea cephamycins

3.Severe H.A.P Use amino glycoside with carbapenems or extended blactams

Surgical site infections

Most commonG+cocci. Staphyloccoccus aureus, Staphylococcus

epidermidis,

Enterococcus faecalis and Escherichia coli, the latter two of which are common pathogens after clean-contaminated surgery.

Antibiotic chosen should be active against Staph1 generation cephalosporins CEFAZOLIN commonly usedThe antibiotic should be given within two hrs of sugery

Single dose prophylaxis is enough

Unless if the patient is undergoing transplant surgery(48 hrs)

Immunocompromised Individuals

Patients with neutropenia

neutropenia is common in hematological malignancies:Such patients predisposed to both gram +Coagulase – staphStre. viridans and g- infectionsEspecially to pseudomonasPatient is said to have low risk neutropenia ifFACTORS ASSOCIATED WITH A LOW RISK OF SEVERE COMPLICATIONS•Malignancy in remission•Absence of co-morbidities (chronic lung disease, diabetes mellitus, congestive heart failure, hemorrhage, liver disease, renal disease)•Absence of vomiting, diarrhea, dehydrationOutpatient status•Absolute monocyte count =100 cells/mm3•Anticipated duration of neutropenia <7–10 days•Normal chest radiograph•Peak temperature <102.2°F (39.0°C)•Absence of shivering•Does not appear ill•Absence of neurologic or mental alterations•Absence of abdominal pain•Absence of intravenous catheter site infection•Absence of septic complications (e.g. severe sepsis, septic shock, hypoxia, pneumonia or other deep organ infection)

In neutro penia IV anti biotics are usedThe anti biotic Should be BACTERICIDAL:,

NON TOXICBROAD SPECTRUM

PREVIOUSLY the initial treatment used to beExtended spectrum pencillin/Antipseudomonal cephalosporin+Aminoglycoside

(Toxic regimen)EORTC-IATG trial showed that mono therapy with ceftriaxone+amikacin is as effective as thrice daily regemen of ceftazidime+amikacinSo now neutropenia patients are treatedMONOTHERAPY 1Carbapenems

2.extended spectrum b lactam/blactamase inhibitor3.3rd and 4th gen. Cephalosporins

And amino glycoside should be added if there is septic shock,severe sepsis,and pseudomonas infection is suspectedAdd vancomycin or linezolid or ortivanacin if sepsis shock and evidence or sucpicion of catheter based infectionIn low risk patients oral fluroquinolones can be give and are effective

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