Dr. Lokesh Garg

M.B.B.S. M.D.

One of the most commonly used group of drugs.

A medical doctor has to know the definite clinical pharmacology of antibiotics, how to select & use them rationally.

- Avoid adverse effects on the patient

- Avoid emergence of antibiotic resistance

- Avoid unnecessary increases in the cost of health care

Definition

Antibiotics are substances that kill or inhibit the growth

of micro-organisms.

Bacteriostatic

Bactericidal

Based on their mechanism of action, antibiotics can be divided into the following classes:

Inhibitors of Cell Wall synthesis Inhibitors of Protein synthesis Inhibitors of Nucleic Acid synthesis

This class includes:

Penicillin Cephalosporin Carbapenems Monobactams Vancomycin Beta lactamase inhibitors

B – lactam antibiotics

Category Parenteral Agents Oral Agents

Natural Penicillins Penicillin G Penicillin V

Antistaphylococcal penicillins

Nafcillin, oxacillin Dicloxacillin

Aminopenicillins Ampicillin Amoxicillin and Ampicillin

Aminopenicillin + -lactamase inhibitor

Ampicillin-sulbactam Amoxicillin-clavulanate

Extended-spectrum penicillin

Piperacillin, ticaricillin Carbenicillin

Extended-spectrum penicillin + -lactamase inhibitor

Piperacillin-tazobactam, ticaricillin-clavulanate

THE PENICILLINS

Class Examples Routes of administration

First generation

Cephalexin/cefadroxilCefazolin

Orali.v.

Second generation

CefuroximeCefoxitin

Oral/ i.v.

Third generation

CefiximeCeftriaxone/cefotaxim

Ceftazidime

Orali.v.i.v.

Fourth generation

Cefipime i.v.

Adverse Effects

Allergic reactions: itch, rash, fever, angioedema, rarely anaphylactic reaction

GI upset and diarrhoea

Interstitial nephritis and increased renal damage in combination with aminoglycosides

Pharmacokinetics

Bactericidal

Safe in pregnancy

Dosage needs to be reduced in cases of impaired renal function.

This class includes:- Macrolides- erythromycin, clarithromycin,

azithromycin

Lincosamides- clindamycin

Aminoglycosides- gentamicin, tobramycin, amikacin, netilmicin,neomycin, streptomycin.

Tetracyclines- tetracycline, doxycycline,minocycline

Chloramphenicol

Pharmacokinetics:

Bacteriostatic

Dose adjustment in renal failure is not necessary

Adverse Effects :

GI upset

Cholestatic jaundice

Prolongation of QT interval (erythromycin)

Theophylline, oral anticoagulants cannot be administered simultaneously

PharmacokineticsPharmacokinetics

Bectericidal

Negligible oral absorption

Dose adjustment is critical in renal impairment

Adverse Effects Ototoxic (permanent)

Avoid concurrent use of other ototoxics drugs for eg. Lasix , minocycline

Nephrotoxic ( reversible): use cautiously with other nephrotoxic drugs

Pharmacokinetics

Bacteriostatic

Best oral absorption in fasting state

Adverse Effects

Contraindicated in renal failure (except doxycycline and minocycline)

Nausea, diarrhoea

Binds to metallic ions in bones and teeth (to be avoided in children and

in pregnancy)

Phototoxic skin reactions

This group includesThis group includes::

Sulphonamides: Sulfamethoxazole, sulfadoxine

Trimethoprim

Quinolones: Ciprofloxacin, levofloxacin, pefloxacin, ofloxacin, norfloxacin, gatifloxacin, moxifloxacin, sparfloxacin

Rifampicin

Azoles: This group includes-

Antibacterial- Metronidazole, secnidazole, tinidazole,

Antihelminth- Albendazole, Mebendazole, thiabendazole

Pharmacokinetics

Bactericidal

Well absorbed orally with good bioavailability

Dose reduction necessary in renal failure

Adverse Effects

Fatal marrow dysplasia and haemolysis in G6PD deficiency

Skin and mucocutaneous reactions: Stevens- Johnson syndrome

Contraindicated in pregnancy

Pharmacokinetics

Bectericidal

Well absorbed after oral administration

Dose adjustment required in renal impairment (except moxifloxacin and trovafloxacin)

These two drugs are contraindicated in hepatic failure

Adverse Effects

GI side effects

CNS effects such as restlessness, headache, insomnia, confusion and seizures in the elderly

Rare skin reactions

Should be avoided in pregnancy

Not routinely recommended for use in patients under 18 years

of age

Pharmacokinetics

Almost completely absorbed after oral administration (60% after rectal administration).

Adverse Effects

Metallic taste

Severe vomiting if taken with alcohol (disulfiram like syndrome )

CNS: Meningitis, brain abscess etc

Respiratory: URTI, Pneumonia, Lung abscess, Bronchiectasis

CVS: Acute rheumatic fever, Infective endocarditis

GIT and HBS: Cholera, Bacillary dysentery, Enteric fever, gastroenteritis, peritonitis,liver abscess

Genitourinary: UTI, pyelonephritis, STDs

Skin : Cellulitis necrotizing fascitis

Musculoskeletal: Osteomyelitis, Septic arthritis

Mycobacterial Infections: Tuberculosis, Leprosy

Chlamydial Infections

Systemic Infections: Sepsis syndrome

62 year old male presents to your clinic with c/o: Cough with expectoration x 4days

◦ Intermittent fever, measured to 100.8◦ Chest pain – Rt side

PMHx

◦ Healthyo No H/O hospitalization in recent pasto not on any medication

Drink socially , non smoker

Exam

VS – temp 100.3, P 92, RR 18, Spo2 - 96% on room air, BP 123/75

HEENT – normal

Neck – normal w/o palpable LN or TMG

Lungs – Bronchial breath sound in I/S , I/A on Rt side, clear at bases,

CV – normal

Legs – no edema

Case 1

Community –acquired Pneumonia (CAP)

Recent onset of - Fever - Productive cough- TLC- CXR

Why CAP- Healthy adult with no H/O hospitalization in recent past & was not taking any antibiotics

Common Outpatient Bacterial Etiologies

AntibioticsAntibiotics

Oral macrolide Erythromycin Azithromycin Clarithromycin

This patient’s pneumonia is mild

Previously healthy

No antibiotics in past 3 months

In patients who are older, have comorbid illnesses Levofloxacin Moxifloxacin

In patients treated with antibiotics within the last 90 days. Respiratory quinolones

MoxifloxacinLevofloxacinGemifloxacin or

B- lactam Amoxicillin + ClavunateCefuroxime

Beta-lactam + macrolide

Ceftriaxone or cefotaxime

Erythromycin, azithromycin, or clarithromycin

OR

Fluoroquinolone with antistreptococcal activity

Levofloxacin or moxifloxacin

Trimethoprim/sulfamethoxizole x 3 days

women with risk factors, complicated UTI

Fluoroquinolone x 3 days: Ciprofloxacin Norfloxacin Ofloxacin

Nitrofurantoin x 7 days

Initial drug selections:

Fluoroquinolones

Ciprofloxacin Levofloxacin

Cephalosorin

Ceftriaxone Cefotaxime + Amikacin

57 years male painful rash on his right leg. 5 days ago he developed a blister on his foot after wearing a new pair of shoes.

c/o fever with chills

PMHx – COPD, high cholesterol

Social – stopped tobacco two years ago.

Exam

Temp 101.2 otherwise stable , APPP

Exam unremarkable except for

Lungs – few inspiratory rales

Right leg …

Outpatient Treatment: non-MRSA

Antistaphylococcal penicillinDicloxacillinFirst-generation cephalosporin Cephalexin

Inpatient Treatment: non-MRSA Amoxicillin + Clavunate

Clindamycin is a good alternate with penicillin allergy

Surgical opinion

A 43 year old male presents with 10 days of purulent rhinorrhea, subjective fevers, and facial

headaches.

PMHx – HTN, high cholesterol

Meds – lisinopril/HCTZ

FamHx – noncontributory

Exam

HEENT – VS normal tenderness over right maxillary sinus

Exam otherwise unremarkable

Diagnosis?

Sinusitis

Mild Acute Bacterial Sinusitis (ABS)Amoxicillin

Amoxicillin/clavulanate

Cefuroxime axetil

CefpodoximeOr

antistrep. fluoroquinolones:LevofloxacinMoxifloxacin

Drug option in the case of allergies to penicillin and cephalosporin with Mild ABS:

◦ Doxycycline

◦ Trimethoprim/sulfamethoxizole

◦ Azithromycin

◦ Clarithromycin

Drug option in the case of allergies to penicillin and cephalosporin with Moderate to Severe ABS:

◦ Antipneumococcal fluoroquinolone:

Levofloxacin Moxifloxacin

42 years male with 5 days of progressive diffuse headache, mildly stiff neck,fever vomiting, confusion.

PMHx – none known

PSHx - none

Exam VS: T 100.9, Pulse 96, RR 16, BP 138/82

Gen: mildly ill appearing

Mental status: orientation to place & person not time

HEENT: mild photophobia

Neck: mild pain with flexion (kernig sign +ve )

Skin: no rash

RS/CVS - WNL

Lab.-

TLC - 16000

DLC - N80 L18

CECT Head - normal study

CSF - TLC – 412DLC – N 96 L4protein – 110mg/dlsuger - 23 mg/dl

Adults(<55years) and children>3 months old: High dose ceftriaxone or cefotaxime

+ Vancomycin 1gm IV BD

Adults > 55years of age , patient with alcoholism or other debilitating illness

High dose ceftriaxone /cefotaxime+ Vancomycin 1gm IV BD

+ Ampicillin 2gm/ 4horly

2gm IV BD

Cholera: Tetracycline 250 mg 6-hourly for 3 days,Doxycycline 300 mg single dose or

Ciprofloxacin 1 g in adults Bacillary Dysentery:

Ciprofloxacin 500 mg 12-hourly for 3 days Helicobacter pylori Infection:

Two antibiotics (from amoxicillin, clarithromycin and metronidazole) for 7 days

Aetiology: Salmonella typhi and Salmonella paratyphi A and B

Ciprofloxacin 500 mg 12-hourly

Ofloxacin 400 mg every 12 hourly

Ceftriaxone 2gm IV BD

Azithromycin 1gm once daily x 5 days

Treatment should be continued for minimum 10 days. Or

5 days after resolution of fever

Aetiology (pyogenic): E.coli, various streptococci (amoebic): Entamoeba

histolytica Management:o Pyogenic: Combination of antibiotics e.g3rd gen

cephalosporin, gentamicin and metronidazole

o Amoebic: Metronidazole (800 mg 8-hourly for 10 days) or tinidazole (2 g daily for 3 days)

Luminal amoebicide-diloxanide furoate (500 mg 8-hourly for 10 days)

Gastro-Intestinal: Ancylostoma, Ascaris:

Albendazole 400 mg single dose or Mebendazole 100 mg 12 hourly for 3 days

Tissue parasite:

Filariasis: Caused by Wuchereria bancrofti

Treatment: Diethylcarbamazine 6 mg/kg body wt. orally in 3 divided doses for 12 days.

Avoid tetracycline Staining of teeth and bones in babies Acute yellow atrophy of lever , pancreatitis in mother

Avoid sulfa drugs in the third trimester May be associated with kernicterus

Avoid aminoglycosides Kidney toxicities Can cause foetal ear damage

Fluoroquinolones Concerns about cartilage development

Treat the Mother first and the baby will appreciate it

Penicillins and cephalosporins are generally safe in pregnancy.

Macrolides are generally safe

- They may increase nausea early on

Is antibiotic necessary

What is the most appropriate antibiotic

H/O

Allergy

Pregnancy

Renal dysfunction

Liver Disease Dose/Frequency/Route/Duration

Monitor side effects