Chemotherapy A- General Considerations and Non-specific Antimicrobial Agents Chapter Notes | Pharmacology - NEET PG PDF Download (2025)

General Considerations

• Antibiotics are substances produced by microorganisms that suppress the growth of or kill other microorganisms at very low concentrations.

Drug Resistance

• Drug resistance in bacteria can be natural or acquired.
• Acquired resistance may result from single-step mutation (e.g., streptomycin, rifampicin) or multi-step mutation (e.g., erythromycin, tetracycline, chloramphenicol).
• Resistance can be transferred between microorganisms via gene transfer, also known as infectious resistance, through the following mechanisms:
  • Conjugation: Physical contact between bacteria leads to multidrug resistance, significant for chloramphenicol and streptomycin resistance.
  • Transduction: Resistance genes are transferred via bacteriophages, affecting drugs like penicillin, erythromycin, and chloramphenicol.
  • Transformation: Resistance genes are transferred through the environment, less clinically significant, e.g., penicillin G.
• Once acquired, resistance becomes prevalent due to selection pressure from widely used antimicrobial agents, allowing resistant organisms to grow preferentially.

Mechanism of Resistance
Microorganisms may develop resistance through:

• Decreased affinity for the target: Altered penicillin-binding proteins in pneumococci and staphylococci reduce drug effectiveness.
• Alternative metabolic pathways: Sulfonamide-resistant organisms utilize preformed folic acid instead of synthesizing it from PABA.
• Enzyme elaboration: Production of inactivating enzymes such as β-lactamases (for penicillins and cephalosporins), chloramphenicol acetyltransferase (for chloramphenicol), and aminoglycoside-inactivating enzymes (for aminoglycosides).
• Decreased drug permeability: Loss of specific channels reduces intracellular drug concentration, affecting aminoglycosides and tetracyclines.
• Efflux pumps: Active extrusion of drugs like tetracyclines, erythromycin, and fluoroquinolones from resistant microorganisms.

Superinfection

• Superinfection is the appearance of a new infection due to antimicrobial therapy.
• Normal microbial flora contributes to host defense by producing bacteriocins and competing with pathogens for nutrients.
• Broad-spectrum antibiotics (e.g., tetracyclines, chloramphenicol, clindamycin, aminoglycosides, ampicillin) may kill normal flora, leading to new infections.
• Common sites for superinfection include the oropharynx, intestine, respiratory, and genitourinary tracts.
• Frequently involved organisms are Candida albicans, Clostridium difficile, staphylococci, Proteus, and Pseudomonas.
• Clostridium difficile superinfection may cause pseudomembranous colitis, most commonly linked to third-generation cephalosporins, with metronidazole as the treatment of choice (vancomycin for severe cases).
• Loss of commensal flora may reduce vitamin K formation, enhancing warfarin’s anticoagulant effects.

Pseudomembranous Colitis

• Most commonly caused by Clostridium difficile.
• Most frequently implicated antimicrobials: third-generation cephalosporins (more common) and clindamycin.
• Treatment of choice: metronidazole.
• Treatment for severe cases: vancomycin.

Concentration Dependent Killing (CDK) and Time Dependent Killing (TDK)

• CDK: Killing effect is higher when the peak concentration to minimum inhibitory concentration (MIC) ratio is greater. Exhibited by aminoglycosides and fluoroquinolones, which are more effective as a large single dose compared to divided doses.
• TDK: Antimicrobial action depends on the duration the drug concentration remains above the MIC. Seen in β-lactams and macrolides, where multiple daily doses are preferred.
• Post-Antibiotic Effect (PAE): After antibiotic exposure, bacterial growth remains suppressed even when drug concentrations fall below the MIC.

Renal Function

• Drugs contraindicated in renal disease: cephalothin, cephaloridine, nitrofurantoin, nalidixic acid, tetracyclines (except doxycycline).
• Drugs requiring dose reduction in renal failure: aminoglycosides, amphotericin B, vancomycin, ethambutol.
• Note: Penicillins and rifampicin do not require dose adjustment in renal disease.

Liver Function

• Drugs contraindicated in liver disease: erythromycin estolate, tetracyclines, pyrazinamide, pefloxacin.
• Drugs requiring dose reduction in liver failure: chloramphenicol, isoniazid, rifampicin, clindamycin.

Genetics Factors

• Antimicrobials causing hemolysis in glucose-6-phosphate dehydrogenase (G-6PD) deficient patients: primaquine, chloroquine, quinine, chloramphenicol, nitrofurantoin, fluoroquinolones, dapsone, sulfonamides.

Classification of Antimicrobial Agents

• Antimicrobials are classified based on mechanism of action and type of action.

Based On the Mechanism of Action

A. Drugs Inhibiting Cell Wall Synthesis:

• Bacterial cell wall contains peptidoglycan with N-acetylmuramic acid and N-acetylglucosamine, plus a pentapeptide unit attached to N-acetylmuramic acid.
• Cell wall synthesis begins with the conversion of UDP-N-acetylglucosamine to UDP-N-acetylmuramic acid by enolpyruvate transferase.
• UDP-M acquires a pentapeptide, facilitated by alanine racemase and alanine-alanine ligase.
• Bactoprenol removes UDP from UDP-M-pentapeptide and adds N-acetylglucosamine, with reactions occurring in the cytoplasm.
• The resulting molecule is transported across the plasma membrane by bactoprenol.
• Peptidoglycan chain elongation occurs via transglycosylase, with strength provided by transpeptidase-mediated cross-linking.
• Antimicrobials secreted in bile: penicillins, ampicillin, nafcillin, cephalosporins, ceftriaxone, cefoperazone, doxycycline, rifampicin, erythromycin.

B. Drugs Inhibiting Protein Synthesis:

• Tetracyclines and Glycylcyclines: Bind to 30S ribosome, inhibiting aminoacyl-tRNA attachment to the A site.
• Chloramphenicol: Binds to 50S ribosome, inhibiting peptidyl transferase, which prevents peptide bond formation and peptide chain transfer from P to A site.
• Macrolides, Lincosamides, Streptogramins: Bind to 50S ribosome, inhibiting translocation of the peptide chain from A to P site.
• Linezolid: Binds to the 23S fraction of 50S ribosome, inhibiting initiation.
• Mnemonic: "Buy AT 30 and SELL at 50" – Aminoglycosides and tetracyclines bind to 30S; streptogramins, erythromycin, lincosamides, linezolid bind to 50S.

C. Drugs Affecting Cell Membrane:

• Cause disruption of the cell membrane, leading to leakage of ions and molecules.
• Polypeptide antibiotics: Polymyxin B, colistin, tyrothricin (bacitracin inhibits cell wall synthesis).
• Polyene antibiotics: Amphotericin B, nystatin, hamycin, natamycin.
• Azoles: Ketoconazole, fluconazole, itraconazole.

D. Drugs Affecting Nucleic Acids (DNA and RNA):

• DNA gyrase inhibitors: DNA gyrase nicks double-stranded DNA, introduces negative supercoils, and reseals ends to prevent excessive supercoiling. In gram-positive bacteria, topoisomerase IV performs a similar function. Inhibitors include quinolones (nalidixic acid, fluoroquinolones) and novobiocin.
• RNA polymerase inhibitors: Rifampicin inhibits transcription by blocking DNA-dependent RNA polymerase.
• Drugs destroying DNA: Metronidazole generates reactive nitro radicals in anaerobic conditions, causing DNA helix destabilization and strand breakage. Nitrofurantoin also destroys DNA.
• Nucleotide/Nucleoside analogues: Structurally similar to nucleosides or nucleotides, these drugs (e.g., idoxuridine, acyclovir, NRTIs) are incorporated into DNA or RNA, forming faulty, non-functional, or unstable nucleic acids.

E. Drugs Affecting Intermediary Metabolism:

• Folic acid synthesis is a key target for inhibition.
• Drugs inhibiting folic acid synthesis: Folic acid synthase (dihydropteroate synthase) incorporates PABA to form folic acid. Sulfonamides, dapsone, and para-aminosalicylic acid (PAS) are competitive inhibitors.
• Dihydrofolate reductase (DHFRase) inhibitors: DHFRase converts dihydrofolic acid to tetrahydrofolic acid, the active form for one-carbon unit transfer. Inhibitors include trimethoprim, pyrimethamine, proguanil, methotrexate.
• Arabinogalactan synthesis inhibitors: Ethambutol inhibits arabinogalactan synthesis, preventing mycolic acid incorporation into mycobacterial cell walls.

Antibiotics According to the Type of Action

• Antibiotics are classified as bacteriostatic (inhibit bacterial growth) or bactericidal (kill bacteria).
• Minimum Bactericidal Concentration (MBC): Concentration of an antibiotic that kills 99.9% of bacteria.
• Minimum Inhibitory Concentration (MIC): Concentration that prevents visible bacterial growth in culture plates using serial dilutions.
• Small difference between MIC and MBC indicates bactericidal action; large difference indicates bacteriostatic action.
• In immunocompromised patients (e.g., HIV, steroid therapy, neutropenic), only bactericidal drugs should be used.

Antibiotic Classification by Action

Bacteriostatic antibiotics:

• Protein synthesis inhibitors: Tetracyclines, Tigecycline, Chloramphenicol, Macrolides, Lincosamides, Linezolid.
• Drugs affecting metabolism: Sulfonamides, Dapsone, PAS, Trimethoprim, Ethambutol.

Bactericidal antibiotics:

• Protein synthesis inhibitors: Aminoglycosides, Streptogramins.
• Drugs affecting DNA: Quinolones, Metronidazole, Nitrofurantoin, Novobiocin.
• Polypeptide antibiotics: Polymixin B, Colistin, Amphotericin B.
• Cell wall synthesis inhibitors: Fosfomycin, Cycloserine, Bacitracin, Vancomycin, Penicillins, Cephalosporins.
• First-line antitubercular (ATT) drugs (except Ethambutol): Rifampicin, Isoniazid, Pyrazinamide, Streptomycin (aminoglycoside).

Based on the Therapeutic Index (TI)

• Therapeutic Index (TI) classifies antibiotics based on safety margin (ratio of toxic dose to effective dose).
• High TI: Penicillins, Cephalosporins, Macrolides.
• Low TI: Chloramphenicol, Aminoglycosides, Tetracyclines.
• Very low TI: Polymixin B, Vancomycin, Amphotericin B.

Drugs Inhibiting Cell Wall Synthesis

• Beta-lactam antibiotics contain a β-lactam ring and inhibit cell wall synthesis.
• Include: Penicillins, Cephalosporins, Monobactams (e.g., Aztreonam), Carbapenems (e.g., Imipenem).
• All β-lactam antibiotics are bactericidal.
• Mechanism: Bind to penicillin-binding proteins (PBPs) on bacterial cell membrane, inhibiting transpeptidase enzyme responsible for cross-linking peptidoglycan chains.
• Bacteria formed in the presence of these drugs lack a cell wall and die due to water imbibition (cell wall provides turgidity).

Penicillins
Penicillin G is derived from Penicillium chrysogenum.

Limitations of Penicillin G:

• Not effective orally due to breakdown by stomach acid.
• Short duration of action due to rapid renal excretion via tubular secretion.
• Narrow spectrum, mainly effective against gram-positive bacteria.
• Resistance due to penicillinase (β-lactamase) or altered PBPs.
• Can cause hypersensitivity reactions.

Newer penicillins developed to address limitations:

• Acid-resistant for oral use: Penicillin V, Oxacillin, Dicloxacillin, Cloxacillin, Amoxycillin, Ampicillin.
• Long-acting formulations:
  • Benzathine and procaine groups added to Penicillin G; Benzathine Penicillin G is the longest-acting.
  • Probenecid inhibits tubular secretion, prolonging action.
  • High initial dose possible due to wide therapeutic index.
• Extended-spectrum penicillins:
  • Aminopenicillins: Ampicillin, Amoxycillin.
  • Carboxypenicillins: Carbenicillin, Ticarcillin.
  • Ureidopenicillins: Mezlocillin, Azlocillin, Piperacillin.
  • Mnemonic: A CT MAP.
  • Effective against gram-negative bacteria (e.g., E. coli, Salmonella, Shigella, except Amoxycillin).
  • CT MAP effective against Pseudomonas; MAP effective against Klebsiella.
• Resistance management:
  • Adding β-lactamase inhibitors to prevent degradation.
  • Penicillinase-resistant penicillins: Cloxacillin, Oxacillin, Nafcillin, Dicloxacillin, Methicillin.
• Hypersensitivity: Penicillins are the most common cause of anaphylactic shock; if severe allergy, avoid all β-lactams except monobactams; intra-dermal skin testing recommended.

Pharmacokinetics:

• One gram of penicillin = 1.6 million units.
• Gastric acid reduces oral bioavailability; Penicillin G used orally only for proven efficacy.
• Ampicillin and Nafcillin partly excreted in bile.
• Penicillin G given by i.m. injection, short half-life (6-12 hourly); Procaine Penicillin (12-24 hourly) and Benzathine Penicillin (longest-acting) have slow release.

Clinical Uses:

• Penicillin G: Drug of choice for syphilis (Benzathine for primary/secondary/early latent as single dose, late latent/tertiary for 3 weeks; Aqueous for neurosyphilis), gram-positive bacteria (streptococci, meningococci), actinomycosis, tetanus (metronidazole preferred), gas gangrene, rat bite fever, yaws, leptospirosis, group A/B streptococcal infections, viridans streptococcal endocarditis; effective against anaerobes except Bacteroides; most staphylococci and gonococci now resistant.
• Methicillin, Nafcillin, Oxacillin, Cloxacillin: For Staphylococcus aureus (methicillin resistance due to altered PBPs; MRSA resistant to all β-lactams, treated with Vancomycin/Teicoplanin; VRSA treated with Linezolid/Streptogramins).
• Ampicillin, Amoxycillin: Wide-spectrum, penicillinase-sensitive; effective against enterococci, Listeria, Haemophilus; enhanced with β-lactamase inhibitors; Ampicillin for Listeria meningitis, UTI by E. faecalis.
• Piperacillin, Ticarcillin, Carbenicillin, Azlocillin, Mezlocillin: Effective against gram-negative rods, including Pseudomonas; used with β-lactamase inhibitors or aminoglycosides; Ureidopenicillins effective against Klebsiella.
• MRSA not susceptible to β-lactam antibiotics.

Toxicity:

• Hypersensitivity (including serum sickness, anaphylaxis); intra-dermal testing required.
• Severe penicillin allergy contraindicates all β-lactams except Aztreonam.
• Ampicillin: Maculopapular rash in viral diseases (e.g., infectious mononucleosis).
• Methicillin: Most common cause of interstitial nephritis.
• Amoxicillin, Ampicillin: Nausea, diarrhea; Ampicillin causes more diarrhea due to incomplete absorption, leading to microbial flora suppression and pseudomembranous colitis.
• Procaine Penicillin: High doses cause seizures, CNS abnormalities.
• Oxacillin: Hepatitis.
• Nafcillin: Neutropenia.
• Carbenicillin: High doses cause bleeding.

Cephalosporins

• β-lactam antibiotics with 7-aminocephalosporanic acid nucleus, classified into five generations.
• First Generation: Cephalexin, Cefadroxil, Cepharadine (oral); Cefazolin (parenteral).
• Second Generation: Cefaclor, Cefuroxime axetil, Loracarbef, Cefprozil (oral); Cefuroxime, Cefotetan, Cefoxitin, Cefmetazole (parenteral).
• Third Generation: Cefixime, Cefpodoxime, Ceftibuten, Cefditoren, Cefdinir (oral); Cefotaxime, Ceftizoxime, Ceftriaxone, Ceftazidime, Cefoperazone, Moxalactam (parenteral).
• Fourth Generation: Cefepime, Cefpirome (parenteral).
• Fifth Generation: Ceftaroline, Ceftobiprole (parenteral).
• Pharmacokinetics:
  • Most excreted via kidney through tubular secretion.
  • Ceftriaxone, Cefoperazone secreted in bile.
  • Nephrotoxicity increased with loop diuretics.
• Antibacterial Spectrum:
  • First Generation: Gram-positive cocci (Streptococci, Staphylococci); not active against penicillin-resistant strains.
  • Second Generation: Gram-negative bacilli (E. coli, Klebsiella, Proteus, H. influenza, M. catarrhalis, Bacteroides); only Cefoxitin, Cefmetazole, Cefotetan effective against Bacteroides.
  • Third Generation: Gram-positive cocci (Streptococci, Staphylococci), gram-negative cocci (Gonococci), gram-negative bacilli (Enterobacteriaceae, Serratia, Pseudomonas), anaerobes (Bacteroides); only Ceftazidime, Cefoperazone effective against Pseudomonas; activity against Bacteroides less than Cefoxitin.
  • Fourth Generation: Same as third generation, more resistant to β-lactamases.
• Clinical Uses:
  • First Generation: Active against gram-positive cocci, including Staphylococci (MRSA resistant); Cefazolin is drug of choice for surgical prophylaxis.
  • Second Generation: Less active against gram-positive organisms than first generation, extended gram-negative coverage; Cefotetan, Cefmetazole, Cefoxitin active against Bacteroides fragilis; Cefuroxime attains higher CSF levels.
  • Third Generation: Active against gram-negative organisms resistant to other β-lactams; penetrate blood-brain barrier (except Cefoperazone, Cefixime); Ceftazidime (maximum), Ceftolozane, Cefoperazone active against Pseudomonas; Ceftazidime for melioidiosis; Ceftizoxime for Bacteroides; Ceftriaxone for gonorrhoea, salmonellosis, E. coli sepsis, Proteus, Serratia, Haemophilus, empirical bacterial meningitis; long-term Ceftriaxone (>2g/d) causes biliary sludging and cholelithiasis; Cefotaxime metabolized to active desacetyl-cefotaxime.
  • Fourth Generation: Active against gram-negative organisms (including Pseudomonas) resistant to third generation; similar efficacy against gram-positive cocci; not active against anaerobes.
• Mnemonics:
  • Generation Identification:
    • Drugs with ‘a’ after cef are first generation (except Cefaclor).
    • Drugs with ‘PI’ are fourth generation (Cefepime, Cefpirome).
    • Drugs with ‘ROL’ are fifth generation (Ceftaroline, Ceftobiprole).
    • Drugs ending in ME (except Cefuroxime), ONE, or TEN are third generation.
    • Others (except Cefdinir, Moxalactam) are second generation.
  • Oral vs. Parenteral:
    • Drugs with ‘OR’ are oral (e.g., Cefaclor, Cefditoren, Loracarbef).
    • Drugs with ‘t’ are injectable (except Ceftibuten).
• Note:
  • Cefotaxime, Ceftriaxone most active against penicillin-resistant pneumococci.
  • No cephalosporin active against Enterococcus faecalis, MRSA, Listeria monocytogenes.
  • Ceftazidime plus aminoglycoside is treatment of choice for Pseudomonas infections.
• Toxicity:
  • Hypersensitivity reactions; complete cross-reactivity between cephalosporins, 5-10% with penicillins.
  • Drugs with methylthiotetrazole group (Cefamandole, Cefoperazone, Moxalactam, Cefotetan) cause hypoprothrombinemia and disulfiram-like reaction with alcohol.
  • Ceftazidime implicated in neutropenia.
• Note: No cephalosporin active against penicillin-resistant Pneumococci, MRSA, Enterococcus, Listeria, Legionella, Xanthomonas, Campylobacter, Clostridium difficile.

Other Beta Lactam Antibiotics

Monobactams:

• Include Aztreonam; active against β-lactamase-producing gram-negative rods, including Pseudomonas; no activity against gram-positive organisms or anaerobes.
• Administered i.v.; half-life prolonged in renal failure.
• Only β-lactam safe for patients with severe penicillin or cephalosporin allergies (no cross-sensitivity).

Carbapenems:

• Include Imipenem, Doripenem, Meropenem, Ertapenem.
• Wide spectrum: gram-positive cocci, gram-negative rods, anaerobes.
• For Pseudomonas (Meropenem most active, Ertapenem least), combine with aminoglycosides.
• β-lactamase resistant; drug of choice for Enterobacter, Klebsiella, Acinetobacter, ESBL-producing organisms.
• Imipenem inactivated by renal dehydropeptidase I, combined with Cilastatin to increase half-life and inhibit nephrotoxic metabolite formation.
• Adverse effects of Imipenem-Cilastatin: Seizures, gastrointestinal distress.
• Meropenem, Doripenem, Ertapenem: Not metabolized by dehydropeptidase, less likely to cause seizures.
• Ertapenem: Long-acting, inactive against Pseudomonas.

Loracarbef:

• Chemically similar to Cefaclor; oral administration; spectrum and uses resemble second-generation cephalosporins.
• Overdose can cause seizures.

Beta Lactamase Inhibitors

• Include Clavulanic acid, Sulbactam, Tazobactam, Avibactam.
• More active against plasmid-encoded β-lactamases (e.g., gonococci, E. coli) than inducible chromosomal β-lactamases (e.g., Pseudomonas, Enterobacter).
• Combinations:
  • Amoxicillin + Clavulanic acid (Co-amoxy-clav).
  • Ampicillin + Sulbactam (Sultamicin).
  • Piperacillin + Tazobactam.
  • Ceftazidime + Avibactam: Approved for complicated UTI (including pyelonephritis) and intra-abdominal infections.

Beta-lactamases

Enzymes that hydrolyze β-lactam antimicrobials; located on chromosome (e.g., SHV-1 in Klebsiella) or plasmid (e.g., penicillin resistance in Staphylococci).

Can be inducible (production triggered by β-lactam exposure, e.g., Staphylococci) or constitutive (constant production, e.g., SHV-1).

Classification:

• Molecular (Amber): Based on structure; Class A, C, D use serine; Class B (metallo-β-lactamases) use zinc.
• Functional (Bush): Based on substrate and inhibition:
• Group 1 (Cephalosporinase, Molecular C): Not inhibited; hydrolyzes cephalosporins, cephamycins, aztreonam (e.g., Amp C).
• Group 2 (Serine β-lactamases, Molecular A or D): Inhibited by Clavulanic acid (CA) or Tazobactam (TZB); includes Penicillinase, Extended Spectrum β-lactamases (ESBL), Carbenicillinase, Oxacillinase.
• Group 3 (Metallo-β-lactamases, Molecular B): Inhibited by EDTA; hydrolyzes carbapenems (e.g., IMP-1).

Extended Spectrum Beta Lactamases (ESBL)

• Enzymes conferring resistance to penicillins, cephalosporins, monobactams; found in gram-negative organisms (primarily Klebsiella, E. coli).
• Characteristics:
  • Bush Group 2be, Amber Group A.
  • Inhibited by Clavulanic acid or Tazobactam.
  • Hydrolyze penicillins, cephalosporins (e.g., Cefotaxime, Ceftazidime, Ceftriaxone, Cefepime), monobactams (Aztreonam).
  • Cannot hydrolyze cephamycins (Cefoxitin, Cefotetan, Cefmetazole) or carbapenems.
  • Carbapenems are drug of choice for ESBL-producing bacteria infections.

Vancomycin and Other Glycopeptides

• Vancomycin: Bactericidal glycopeptide; inhibits cell wall synthesis by inhibiting transglycosylase enzyme.
• Narrow spectrum; effective against gram-positive organisms (MRSA, penicillin-resistant pneumococci, Clostridium difficile).
• Drug of choice for MRSA, Corynebacterium jeikeium, serious infections in penicillin-allergic patients.
• Teicoplanin: Similar to Vancomycin; once-daily dosing due to long half-life (45-70 hours); no red man syndrome or nephrotoxicity.
• Administration: Vancomycin (i.v.), Teicoplanin (i.v. or i.m.); excreted unchanged in urine.
• Rapid i.v. Vancomycin infusion causes Red Man Syndrome (flushing due to histamine release).
• Vancomycin toxicities: Chills, ototoxicity, nephrotoxicity; reduce dose in renal failure.
• Vancomycin: Oral use for Clostridium difficile pseudomembranous colitis (not absorbed, high colon concentration).
• Oritavancin: Newer glycopeptide for MRSA infections.
• Telavancin: Approved for complicated skin infections; effective against MRSA; disrupts membrane potential.
• Dalbavancin: Once-weekly for MRSA and VRSA; same mechanism as Vancomycin.

Fosfomycin

• Inhibits cell wall synthesis by inhibiting enolpyruvate transferase.
• Drug of choice (with Nitrofurantoin) for uncomplicated urinary tract infections.
• Common side effect: Diarrhea.

Bacitracin

• Inhibits cell wall synthesis; marked nephrotoxicity limits to topical use.
• Selective against gram-positive bacteria.

Cycloserine

• Inhibits cell wall synthesis; second-line drug for tuberculosis.
• Toxicities: Neurotoxic effects (tremors, seizures), neuropsychiatric symptoms.

Drugs Inhibiting Protein Synthesis

Classified by spectrum:

• Broad spectrum: Chloramphenicol, Tetracyclines.
• Moderate spectrum: Macrolides, Ketolides.
• Narrow spectrum: Lincosamides, Streptogramins, Oxazolidinones.

Chloramphenicol

• Inhibits protein synthesis by binding to 50S ribosomal subunit, inhibiting peptidyl transferase.
• Bacteriostatic, broad-spectrum; undergoes enterohepatic circulation, inactivated by hepatic glucuronidation.
• Resistance due to acetyl transferase enzyme.
• Limited systemic use due to resistance and toxicity; previously used for typhoid (now Ceftriaxone/Ciprofloxacin preferred).
• Active against anaerobes; may cause superinfection diarrhea.
• Toxicities: Dose-dependent reversible bone marrow suppression; idiosyncratic irreversible myelosuppression (even ocular use); Grey Baby Syndrome in neonates/premature infants (decreased RBCs, cyanosis, cardiovascular collapse) due to deficient hepatic glucuronyl transferase.

Tetracyclines

• Inhibit protein synthesis by binding to 30S ribosomal subunit, preventing aminoacyl-tRNA binding.

Groups:

• Group I: Tetracycline, Chlortetracycline, Oxytetracycline.
• Group II: Demeclocycline, Lymecycline.
• Group III: Doxycycline, Minocycline.

Pharmacokinetics:

• Oral absorption impaired by food, multivalent cations (calcium, iron, aluminum); yogurt reduces absorption.
• Cross placenta, affect fetus.
• Undergo enterohepatic circulation.
• Excreted in urine (except Doxycycline, excreted in feces, safe in renal failure).
• Doxycycline, Minocycline have longer half-lives.

Clinical Uses:

• Broad-spectrum bacteriostatic; resistance due to efflux pumps.
• First-choice for: Lymphogranuloma venereum, Granuloma inguinale, Atypical pneumonia (Chlamydia), Cholera, Brucellosis (with Rifampicin), Plague prophylaxis (Streptomycin for treatment), Relapsing fever (Doxycycline), Lyme’s disease (Doxycycline), Rickettsial infections (Doxycycline), Chlamydial infections (Doxycycline).
• Other uses: Meningococcal carrier state (Minocycline), Malaria prophylaxis (Doxycycline), Amoebiasis (Doxycycline), SIADH (Demeclocycline), Pleurodesmosis in malignant pleural effusion, Leprosy (Minocycline), secondary for gonorrhoea, syphilis, chlamydial infections, H. pylori peptic ulcer (Tetracycline).

Toxicity:

• Superinfection diarrhea, pseudomembranous colitis; gastrointestinal effects most common.
• Contraindicated in pregnancy (fetal tooth enamel dysplasia, bone growth irregularities).
• In children <8 years, causes dentition abnormalities (Doxycycline less likely).
• High doses cause hepatic necrosis, especially in pregnancy.
• Outdated Tetracycline causes Fanconi’s syndrome (renal tubular acidosis).
• Exacerbate pre-existing renal dysfunction, not directly nephrotoxic.
• Photosensitivity: Demeclocycline (maximum), Doxycycline.
• Vestibular toxicity: Minocycline (dose-dependent, more in women).
• Diabetes insipidus: Demeclocycline (ADH antagonist).
• Anti-anabolic effects.

Mnemonic (KAPILDE V):

• K: Kidney Failure (all contraindicated except Doxycycline).
• A: Antianabolic effect.
• P: Photosensitivity (maximum Demeclocycline).
• I: Insipidus (diabetes insipidus, maximum Demeclocycline).
• L: Liver Toxicity (hepatic necrosis).
• D: Dentition and Bone defects (contraindicated in pregnancy, children).
• E: Expired drugs cause Fanconi’s syndrome.
• V: Vestibular dysfunction (maximum Minocycline).

Glycylcyclines

• Include Tigecycline; inhibit protein synthesis similar to Tetracyclines, more resistant to efflux pumps.
• Indications: Serious complicated skin/structure infections, intra-abdominal infections.
• Broad spectrum: MRSA, VRSA, Streptococci, Enterococci, anaerobes, Rickettsia, Chlamydia, Legionella, rapidly growing mycobacteria.
• Ineffective against Proteus, Pseudomonas.

Macrolides

Large cyclic lactone ring with attached sugars; include Erythromycin, Azithromycin, Roxithromycin, Clarithromycin, Tacrolimus (immunosuppressant).

Inhibit protein synthesis by binding to 50S ribosome, blocking peptide chain translocation.

Pharmacokinetics:

• Well absorbed orally.
• Erythromycin: Biliary excretion; Clarithromycin: Renal and biliary; Azithromycin: Slow excretion, mainly urine, longest half-life.
• Erythromycin: Four times daily; Azithromycin: Single daily dose.

Clinical Uses (CLAW):

• Chancroid (Haemophilus ducreyi, Azithromycin single dose), Corynebacterium (diphtheria), Campylobacter.
• Legionella infections.
• Atypical pneumonia.
• Whooping cough (Bordetella pertussis).
• Second-choice for Chlamydia, gram-positive organisms (to Penicillins).
• Azithromycin: More active against H. influenza, Neisseria; single dose for urogenital Chlamydia; once-weekly for MAC prophylaxis.
• Roxithromycin: Similar spectrum to Azithromycin.
• Clarithromycin: For MAC prophylaxis/treatment, H. pylori peptic ulcer.
• Anti-inflammatory action: Prevents cystic fibrosis exacerbation.
• Spiramycin: Drug of choice for toxoplasmosis in pregnancy.
• Fidaxomycin: Non-absorbed, for C. difficile infection.

Toxicity:

• Gastrointestinal effects (most common); Erythromycin stimulates motilin receptors, causing diarrhea.
• Erythromycin estolate: Acute cholestatic hepatitis, especially in pregnancy (other salts safe).
• Erythromycin, Roxithromycin, Clarithromycin inhibit CYP3A4, causing QT prolongation with Terfenadine, Astemizole, Cisapride (torsades de pointes); Azithromycin free from these interactions.
• Intravenous Erythromycin: Dose-dependent reversible ototoxicity.
• Erythromycin increases Theophylline concentration by inhibiting CYP1A2.

Ketolides

• Include Telithromycin; same mechanism and indications as Macrolides.
• Excreted in bile and urine; potent CYP3A4 inhibitor.

Lincosamides

• Include Clindamycin, Lincomycin; same mechanism as Macrolides.
• Clindamycin: Effective against anaerobes (Bacteroides, Propionibacterium), severe invasive group A streptococcal infections (with Penicillin), Pneumocystis jiroveci, Toxoplasma gondii; alternative to Amoxycillin/Ampicillin for endocarditis prophylaxis.
• Previously most common cause of pseudomembranous colitis (now second/third-generation Cephalosporins).
• Can cause hepatic dysfunction.

Streptogramins

• Bactericidal; bind to 50S ribosomal subunit, constrict exit channel, inhibit tRNA synthetase.
• Quinpristin-Dalfopristin: Bactericidal combination with prolonged post-antibiotic effect (PAE).
• Effective against penicillin-resistant pneumococci, Methicillin-resistant Enterococcus faecium (not faecalis), MRSA, VRSA.
• MLS-B resistance: Cross-resistance with Macrolides, Lincosamides.
• Potent CYP3A4 inhibitors; drug interactions possible.
• Side effects: Venous irritation (requires central line), arthralgia-myalgia syndrome.

Oxazolidinones

• Include Linezolid, Tedizolide; bind to 23S part of 50S ribosomal subunit, inhibit initiation of protein synthesis.
• No cross-resistance with other protein synthesis inhibitors.
• Effective against MRSA, VRSA, vancomycin-resistant Enterococcus faecium/faecalis.
• Toxicities: Thrombocytopenia, neutropenia (monitor blood counts if therapy >1 week), MAO inhibitory activity (serotonin syndrome with SSRIs), optic neuritis, peripheral neuropathy, lactic acidosis.

Aminoglycosides

• Include Streptomycin, Gentamicin, Kanamycin, Tobramycin, Amikacin, Sisomicin, Netilmicin, Neomycin, Framycetin.
• Bactericidal; inhibit protein synthesis; oxygen-dependent transport limits activity against anaerobes.
• Enhanced penetration with cell wall synthesis inhibitors (e.g., Penicillins).
• Bind to 30S/50S ribosomes, freeze initiation, interfere with polysome formation, cause mRNA misreading.
• Pharmacokinetics:
  • Not absorbed orally, do not cross blood-brain barrier.
  • Excreted by glomerular filtration; reduce dose in renal insufficiency.
  • Resistance due to inactivating enzymes (acetylate, phosphorylate, adenylate); Amikacin, Netilmicin less susceptible.

Clinical Uses:

• Gentamicin, Tobramycin, Amikacin: Effective against gram-negative organisms, including Pseudomonas (except Salmonella); not reliable alone for gram-positive organisms.
• Synergistic with β-lactams or Vancomycin against gram-positive bacteria.
• Streptomycin: First-line for tuberculosis, plague, tularemia.
• Amikacin: Second-line for tuberculosis, MDR tuberculosis.
• Netilmicin: For serious infections.
• Neomycin, Framycetin: Topical use due to high toxicity; Neomycin orally for gut sterilization in hepatic encephalopathy.
• Spectinomycin: Single-dose for penicillinase-producing Neisseria gonorrhoea (PPNG), gonorrhea in penicillin-allergic patients.
• Note: Tobramycin less active than Gentamicin/Streptomycin for enterococcal endocarditis.

Toxicity:

• Ototoxicity: Damages hair cells; irreversible, progresses from high to low frequencies; early changes reversible with Ca2+; Amikacin (maximum hearing loss), Streptomycin (maximum vestibular dysfunction), Netilmicin (least ototoxic).
• Nephrotoxicity: Proximal tubular cell toxicity, reversible; Neomycin most nephrotoxic (not systemic), Gentamicin > Tobramycin > Streptomycin (least).
• Neuromuscular blockade: Rare, severe respiratory depression; Neomycin, Streptomycin (maximum), Tobramycin (least); avoid in myasthenia gravis; reversible with i.v. calcium.

Toxicity Ranking:

• Nephrotoxicity: Neomycin > Gentamicin > Streptomycin.
• Ototoxicity: Amikacin (auditory), Streptomycin (vestibular) > Netilmicin.
• Neuromuscular blockade: Neomycin > Streptomycin > Tobramycin.

Pleuromutilins

• Retapamulin: A topical drug approved for impetigo caused by methicillin-sensitive Staphylococcus aureus or Streptococcus pyogenes.
• Mechanism: Inhibits protein synthesis by binding to 50S ribosomes.

• Antimetabolites interfere with the role of endogenous compounds in cellular metabolism.
• Examples: sulfonamides, trimethoprim, pyrimethamine, proguanil, methotrexate.

Sulfonamides

• Bacteriostatic agents that competitively inhibit folate synthase.
• Selective toxicity to bacteria because mammalian cells utilize preformed folic acid from the diet, not synthesizing it.
• Ineffective in the presence of pus due to high PABA content.
• Undergo hepatic metabolism by acetylation (along with dapsone, hydralazine, isoniazid, procainamide), which may cause systemic lupus erythematosus (SLE).
• Precipitation in acidic urine can lead to crystalluria; risk is minimal with soluble drugs like sulfisoxazole.
• Sulfadoxine: Longest-acting sulfonamide.
• Sulfacytine: Shortest-acting sulfonamide.
• Classification:
  • For systemic use (oral):
    • Short-acting: sulfisoxazole, sulfamethiazole, sulfacytine.
    • Intermediate-acting: Not specified in the document.
    • Long-acting: sulfadoxine.
  • For gastrointestinal tract (GIT): sulfasalazine, olsalazine.
  • For topical use: sulfacetamide, silver sulfadiazine, mafenide.
• Clinical Uses:
  • Sulfacetamide: Ocular infections.
  • Mafenide, silver sulfadiazine: Topical treatment for burn patients.
  • Sulfadiazine: Nocardiosis.
  • Sulfisoxazole: Urinary tract infections (UTIs).
  • Sulfasalazine, olsalazine: Ulcerative colitis.
  • Sulfadoxine + pyrimethamine: Malaria.
  • Sulfadiazine + pyrimethamine: Toxoplasmosis, prophylaxis of Pneumocystis jiroveci pneumonia in AIDS patients.
• Toxicity:
  • Most common: Hypersensitivity-induced skin rash.
  • Can cause granulocytopenia, thrombocytopenia, aplastic anemia (more common in treated patients).
  • Acute hemolysis in G-6PD deficient patients.
  • Crystalluria and hematuria due to precipitation in acidic urine.
  • Kernicterus in newborns if given in the third trimester of pregnancy due to bilirubin displacement from plasma protein binding sites.

Trimethoprim

• Bacteriostatic antimetabolite that inhibits dihydrofolate reductase (DHFRase).
• Achieves high concentrations in prostate and vaginal fluids.
• Commonly combined with sulfonamides but can be used alone for prostatitis and UTIs.
• Adverse effects: Megaloblastic anemia (in folate deficiency), hyperkalemia (due to amiloride-like inhibition of epithelial Na⁺ channels in collecting ducts).
• Other DHFRase inhibitors: pyrimethamine, methotrexate, proguanil, pentamidine, all of which can cause megaloblastic anemia.

Cotrimoxazole

• Fixed-dose combination of sulfamethoxazole and trimethoprim (5:1 ratio).
• Both drugs have similar half-lives; plasma concentration ratio achieved is 20:1 due to differences in bioavailability (higher for sulfamethoxazole).
• Bactericidal due to sequential blockade of DNA synthesis: sulfamethoxazole inhibits folate synthase, and trimethoprim inhibits DHFRase.
• Effective for UTIs, respiratory tract infections, MRSA, middle ear and sinus infections caused by Haemophilus and Moraxella.
• Drug of choice for pneumocystosis and nocardiosis.
• Adverse effects are similar to those of sulfonamides and trimethoprim.

Fluoroquinolones

• Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV, preventing DNA replication.
• Exhibit a long post-antibiotic effect (PAE).
• Classification by Spectrum:
  • First generation: Norfloxacin, lomefloxacin (narrow spectrum, mainly gram-negative).
  • Second generation: Ciprofloxacin, ofloxacin.
  • Third generation: Levofloxacin, gatifloxacin, pefloxacin, sparfloxacin (more active against gram-positive).
  • Fourth generation: Moxifloxacin, fleroxacin, garenoxacin, gemifloxacin, trovafloxacin (broadest spectrum).
• Pharmacokinetics:
  • Good oral bioavailability (except norfloxacin).
  • Absorption impaired by multivalent cations (e.g., calcium, magnesium).
  • Metabolism: Hepatic metabolism and biliary excretion for most; sparfloxacin and pefloxacin are excreted by both renal and hepatic routes.
  • Excretion: Ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, norfloxacin, ofloxacin are excreted via tubular secretion in kidneys, inhibited by probenecid.
  • Dose adjustment required in renal disease for all fluoroquinolones.
• Clinical Uses:
  • Most active oral agents against Pseudomonas (ciprofloxacin has maximum activity).
  • First-generation (e.g., norfloxacin): Bactericidal urine concentrations for UTIs but not effective systemically.
  • Second-generation (e.g., ciprofloxacin, ofloxacin): Effective against gonorrhea, gram-negative organisms, and Pseudomonas. Ciprofloxacin is the drug of choice for anthrax prophylaxis/treatment and meningococcal meningitis prophylaxis.
  • Ciprofloxacin and levofloxacin: Only fluoroquinolones effective against Pseudomonas.
  • Levofloxacin: L-isomer of ofloxacin, effective against atypical microorganisms (e.g., Mycoplasma).
  • Sparfloxacin: Greater activity against gram-positive organisms but not Pseudomonas.
  • Respiratory fluoroquinolones (levofloxacin, gatifloxacin, gemifloxacin, moxifloxacin): Enhanced activity against gram-positive and atypical organisms (e.g., Chlamydia, Mycoplasma, Legionella).
  • Moxifloxacin, trovafloxacin: Broadest spectrum, including gram-negative, gram-positive, and anaerobes.
  • Ciprofloxacin, levofloxacin, moxifloxacin: Effective in tuberculosis and for prophylaxis in neutropenic patients.
  • Finafloxacin: Recently approved for topical treatment of acute otitis externa caused by Pseudomonas and Staphylococcus.
  • Treponema pallidum and Nocardia are resistant to all fluoroquinolones.
• Toxicity:
  • Most common: Gastrointestinal distress, followed by CNS side effects (headache, dizziness, rarely seizures).
  • Cartilage problems: Not recommended for children under 18 or pregnant women, except when benefits outweigh risks (e.g., cystic fibrosis with pulmonary exacerbations).
  • Tendinitis and tendon rupture: Rare in adults.
  • Phototoxicity: Highest with lomefloxacin and sparfloxacin.
  • Gatifloxacin: Withdrawn in India due to dysglycemic effects (hypo- or hyperglycemia).
  • Moxifloxacin: Can cause hypoglycemia.
  • Sparfloxacin, gatifloxacin: Prolong QTc interval (grepafloxacin withdrawn due to arrhythmias).
  • Trovafloxacin: Hepatotoxic potential.
  • Ciprofloxacin, pefloxacin: Increase plasma concentrations of methylxanthines (e.g., theophylline), enhancing toxicity.
  • NSAIDs: Increase CNS toxicity (seizures) of fluoroquinolones; contraindicated in epilepsy.
  • Withdrawn fluoroquinolones: Temafloxacin (immune hemolytic anemia), trovafloxacin (hepatotoxicity), grepafloxacin (cardiotoxicity), clinafloxacin (phototoxicity).
  • FDA warning: Peripheral neuropathy associated with fluoroquinolones.

Urinary Antiseptics

• Oral drugs rapidly excreted in urine, suppressing bacterial growth in the urinary tract.
• More effective in acidic urine, as low pH independently inhibits bacterial growth.
• Key drugs: nitrofurantoin, methenamine mandelate, nalidixic acid.

Nitrofurantoin

• After reduction by bacterial enzymes, causes DNA damage.
• Active against most urinary pathogens except Pseudomonas and Proteus.
• Resistance develops slowly.
• Used infrequently now.
• Adverse effects: Diarrhea, phototoxicity, neurotoxicity, hemolysis in G-6PD deficient patients.

Methanamine Mandelate

• Releases formaldehyde at low pH (<5.5), which provides antibacterial activity.
• Mandelate salt acidifies urine, enhancing effectiveness.
• Ineffective against Proteus, which releases ammonia and alkalinizes urine.
• Forms insoluble complexes with sulfonamides, so should not be co-administered.

Nalidixic Acid

• Quinolone drug that inhibits DNA gyrase.
• Ineffective against Pseudomonas and Proteus.
• Resistance emerges rapidly.
• Main adverse effect: Neurotoxicity.

Phenazopyridine

• Not a urinary antiseptic but an analgesic that alleviates dysuria, frequency, burning, and urgency.

Other Antibacterial Drugs

• Include daptomycin, mupirocin, polypeptide antibiotics, fusidic acid, teicoplanin, glycylcyclines.

Daptomycin

• Lipopeptide bactericidal drug causing depolarization of bacterial cell membranes with K⁺ efflux, leading to rapid cell death.
• Used for serious gram-positive infections, including penicillin-resistant pneumococci, MRSA, and VRSA.
• Effective against organisms resistant to linezolid and streptogramins.
• Dose-limiting toxicity: Myopathy.
• Pulmonary surfactant antagonizes daptomycin, so it should not be used for pneumonia.

Mupirocin (Pseudomonic Acid)

• Inhibits protein synthesis by binding to isoleucyl-tRNA.
• Active against most gram-positive cocci, including MRSA (but not enterococci).
• Used topically or nasally to eliminate staphylococcal nasal carriage.

Polypeptide Antibiotics

• Include polymyxin B, bacitracin, colistin, tyrothricin.
• All except bacitracin affect the cell membrane; bacitracin inhibits cell wall synthesis.
• Used topically due to neurotoxicity and renal damage.

Fusidic Acid

• Blocks protein synthesis.
• Used topically for staphylococcal infections.

Important Points About Antimicrobials

Major Routes of Drug Elimination:

• Renal: Aminoglycosides, amphotericin B, beta-lactams, quinolones, sulfonamides, tetracyclines.
• Hepatic/Biliary: Metronidazole, erythromycin, ceftriaxone, azithromycin, novobiocin, linezolid, isoniazid, streptogramins, moxifloxacin, clindamycin, cefoperazone, doxycycline, ampicillin, nafcillin, rifampicin, chloramphenicol.
  

​Drugs Effective Against Anaerobic Organisms: Clindamycin, cefmetazole, metronidazole, cefotetan, trovafloxacin, chloramphenicol, cefoxitin, moxifloxacin, vancomycin.

• Note: Aminoglycosides are ineffective against anaerobes.

Drugs Effective Against Pseudomonas:

• Beta-lactam antibiotics: Carboxypenicillins (carbenicillin, ticarcillin), ureidopenicillins (piperacillin, azlocillin, mezlocillin), carbapenems (imipenem, doripenem, meropenem), monobactams (aztreonam), cephalosporins (ceftazidime, cefoperazone, moxalactam, cefepime, cefpirome).
• Fluoroquinolones: Ciprofloxacin, pefloxacin.
• Polypeptide antibiotics: Colistin, polymyxin B.
• Aminoglycosides: Effective against Pseudomonas.
• Note: Vancomycin is not active against Pseudomonas.
• Treatment of choice: Ceftazidime plus an aminoglycoside.

Drugs Effective Against MRSA: Vancomycin, teicoplanin, oritavancin, telavancin, dalbavancin, streptogramins, linezolid, daptomycin, cotrimoxazole, rifampicin, tetracyclines.

• Note: No β-lactams are effective against MRSA except fifth-generation cephalosporins.
  

Antimicrobials of Choice for Prophylaxis:

• Cholera: Tetracycline.
• Rheumatic fever: Benzathine penicillin.
• Tuberculosis: Isoniazid alone or with rifampicin.
• Meningococcal meningitis: Rifampicin, ciprofloxacin, ceftriaxone.
• Gonorrhea/Syphilis: Procaine penicillin.
• Rickettsial infections: Tetracyclines.
• Malaria: Chloroquine, mefloquine, doxycycline.
• Influenza A and B: Oseltamivir.
• Surgical prophylaxis: Cefazolin.
• Anthrax: Ciprofloxacin, doxycycline.
• Diphtheria: Penicillin, erythromycin.
• Endocarditis: Amoxicillin, clindamycin.
• Herpes simplex: Acyclovir.
• Group B streptococcal infection: Ampicillin.
• Haemophilus influenzae type B: Rifampicin.
• Mycobacterium avium complex (MAC): Azithromycin, clarithromycin, rifabutin.
• Otitis media: Amoxicillin.
• Pertussis: Azithromycin.
• Plague: Tetracycline.
• Pneumocystis jiroveci: Cotrimoxazole, dapsone, atovaquone.
• Toxoplasmosis: Cotrimoxazole.
• Urinary tract infections: Cotrimoxazole.
• Most Important Mechanism of Drug Resistance:
  • Beta-lactams: Inactivating enzyme (β-lactamase).
  • Tetracyclines: Efflux pump (decreased intracellular concentration).
  • Chloramphenicol: Inactivating enzyme (acetyltransferase).
  • Aminoglycosides: Inactivating enzyme.
  • Macrolides: Decreased permeability or efflux pumps.
  • Sulfonamides: Increased PABA production, decreased folate synthase activity.
  • Fluoroquinolones: Altered DNA gyrase with reduced affinity.
  • Note: Resistance transfer is plasmid-mediated for all antibiotics except fluoroquinolones (chromosomal mutation).

Drugs of Choice For Suspected or Proved Microbial Pathogens

Gram-Positive Cocci:

• Streptococcus:
  • S. pneumoniae: Penicillin G.
  • Hemolytic groups A, B, C, G: Penicillin G.
  • S. viridans: Penicillin G.
• Staphylococcus:
  • Non-penicillinase producing: Penicillin G.
  • Penicillinase producing: Penicillinase-resistant penicillin (cloxacillin, oxacillin, nafcillin, dicloxacillin).
  • Methicillin-resistant (MRSA): Vancomycin.
  • Coagulase-negative: Vancomycin.
• Enterococcus:
  • E. faecalis: Ampicillin.
  • E. faecium: Vancomycin.

Gram-Positive Bacilli:

• Actinomyces: Penicillin G.
• Bacillus:
  • Anthracis: Ciprofloxacin or doxycycline.
  • Cereus and others: Penicillin G.
• Clostridium: Penicillin G.
• Corynebacterium: Erythromycin.
• Listeria: Ampicillin.

Gram-Negative Cocci:

• Neisseria:
  • Meningitidis: Penicillin G.
  • Gonorrhoeae: Ceftriaxone + azithromycin/doxycycline.
• Moraxella: Fluoroquinolones.

Gram-Negative Bacilli:

• Campylobacter: Macrolides.
• Legionella: Macrolides.
• Bordetella: Macrolides.
• Brucella: Doxycycline + rifampicin.
• Acinetobacter: Carbapenems.
• Haemophilus:
  • Serious infections (e.g., meningitis): Ceftriaxone.
  • Respiratory infections, otitis: Cotrimoxazole.
  • Ducreyi (chancroid): Azithromycin.
• Prevotella: Clindamycin.
• Bacteroides: Metronidazole.
• Pseudomonas: Anti-pseudomonal β-lactam (piperacillin, ceftazidime, cefepime, imipenem) + gentamicin.

Examples of Initial Antimicrobial Therapy for Acutely Ill, Hospitalized Adults Pending Identification of Causative Organism

• Bacterial Meningitis:
  • Age 18–50 years: Vancomycin + ceftriaxone.
  • Age >50 years: Vancomycin + ceftriaxone + ampicillin (to cover Listeria).
  • Post-operative or post-traumatic: Vancomycin + cefepime.
• Brain Abscess: Vancomycin + ceftriaxone + metronidazole.
• Pneumonia:
  • Community-acquired: Respiratory fluoroquinolone (levofloxacin, moxifloxacin, gemifloxacin) or azithromycin + ceftriaxone.
  • Nosocomial:
    • Low risk of MDR organisms: Respiratory fluoroquinolone.
    • High risk of MDR organisms: Ceftazidime + gentamicin (to cover Pseudomonas) + vancomycin (for MRSA).
• Endocarditis: Vancomycin + gentamicin.
• Septic Thrombophlebitis: Vancomycin + ceftriaxone.
• Osteomyelitis: Nafcillin or cefazolin.
• Septic Arthritis: Ceftriaxone.
• Pyelonephritis: Ceftriaxone.
• Febrile Neutropenia: Ceftazidime.
• Intra-abdominal Sepsis: Ertapenem.

Example of Empiric Choices of Antimicrobials for Adult Outpatient Infections

• Streptococcal Skin Infections:
  • Erysipelas: Penicillin V.
  • Impetigo: Penicillin V.
  • Cellulitis: Penicillin V.
  • Lymphangitis: Penicillin V.
• Staphylococcal Skin Infection:
  • Furuncle: Dicloxacillin.
• Pharyngitis: Penicillin V.
• Otitis Media: Amoxicillin.
• Malignant Otitis Externa: Ciprofloxacin.
• Acute Sinusitis: Amoxicillin.
• Pneumonia:
  • Aspiration: Clindamycin.
  • Community-acquired: Doxycycline or azithromycin.
• Urinary Tract Infections:
  • Cystitis: Nitrofurantoin or fosfomycin.
  • Pyelonephritis: Fluoroquinolone.
• Gastroenteritis:
  • Salmonella: No treatment.
  • Shigella: Ciprofloxacin.
  • Campylobacter: Ciprofloxacin.
  • Entamoeba: Metronidazole.
• Urethritis or Epididymitis:
  • Gonococcal: Ceftriaxone + azithromycin.
  • Chlamydial: Doxycycline.
• Pelvic Inflammatory Disease (PID): Fluoroquinolone + metronidazole.
• Syphilis:
  • Early (primary, secondary, latent <1 year): Benzathine penicillin G once.
  • Latent >1 year: Benzathine penicillin G for 3 weeks.
  • Cardiovascular: Benzathine penicillin G for 3 weeks.
  • Neurosyphilis: Aqueous penicillin G for 10–14 days.