Anti Tuberculosis Drugs

Antituberculosis drugs •

To avoid the emergence of resistant organisms, compound therapy is used (e.g. three drugs initially, followed by a two-drug regimen later).

First-line drugs •

•

•

•

Isoniazid kills actively growing mycobacteria within host cells; mechanism of action unknown. Given orally, it penetrates necrotic lesions, also the cerebrospinal fluid (CSF). 'Slow acetylators' (genetically determined) respond well. It has low toxicity. Pyridoxine deficiency increases risk of neurotoxicity. No cross-resistance with other agents. Rifampicin (rifampin ) is a potent, orally active drug that inhibits mycobacterial RNA polymerase. It penetrates CSF. Unwanted effects are infrequent (but serious liver damage has occurred). It induces hepatic drugmetabolising enzymes. Resistance can develop rapidly. Ethambutol inhibits growth of mycobacteria by an unknown mechanism. It is given orally and can penetrate CSF. Unwanted effects are uncommon, but optic neuritis can occur. Resistance can emerge rapidly. Pyrazinamide is tuberculostatic against intracellular mycobacteria by an unknown mechanism. Given orally, it penetrates CSF. Resistance can develop rapidly. Unwanted effects include increased plasma urate and liver toxicity with high doses.

Second-line drugs • •

•

Capreomycin is given intramuscularly. Unwanted effects include damage to kidney and to eighth nerve. Cycloserine is a broad-spectrum agent. It inhibits an early stage of peptidoglycan synthesis. Given orally, it penetrates the CSF. Unwanted effects affect mostly central nervous system. Streptomycin, an aminoglycoside antibiotic, acts by inhibiting bacterial protein synthesis. It is given intramuscularly. Unwanted effects are ototoxicity (mainly vestibular) and nephrotoxicity.

Table 46-1. General choice of antibiotics against common or important micro-organisms

Micro-organism(s)b

First-choice antibiotic(s)c Gram-positive cocci Staphylococcus (boils, infection of wounds, etc.) Non-β-lactamaseBenzylpenicillin producing (penicillin G) or phenoxymethylpenicillin (penicillin V) β-lactamase-producing A β-lactamase-resistant penicillin (e.g. flucloxacillin) Methicillin-resistant

Vancomycin ±gentamicin ±rifampicin (rifampin )

Methicillin/vancomycinresistant Streptococcus, haemolytic types (septic infections, e.g. bacteraemia, scarlet fever, toxic shock syndrome) Enterococcus (endocarditis)

Quinupristin/dalfopristin or linezolid Benzylpenicillin or phenoxymethylpenicillin ±an aminoglycoside

Benzylpenicillin +gentamicin Pneumococcus (pneumonia) Benzylpenicillin or phenoxymethylpenicillin or ampicillin , or a macrolide Gram-negative cocci Morasella catarrhalis (sinusitis) Amoxicillin +clavulanic acid Neisseria gonorrhoeae Amoxicillin +clavulanic (gonorrhoea) acid, or ceftriaxone Neisseria meningitidis Benzylpenicillin (meningitis)

Corynebacterium (diphtheria)

Gram-positive rods A macrolide

Second-choice antibiotic(s)c

A cephalosporin or vancomycin

A cephalosporin or vancomycin, or a macrolide, or a quinolone Co-trimoxazole, or ciprofloxacin, or a macrolide ±fusidic acid, or rifampicin A cephalosporin, or a macrolide, or vancomycin. Vancomycin A cephalosporin

Ciproxafloxacin Cefotaxime, or a quinolone Chloramphenicol , or cefotaxime, or minocycline Benzylpenicillin

Micro-organism(s)b Clostridium (tetanus, gangrene) Listeria monocytogenes (rare cause of meningitis and generalised infection in neonates)

First-choice antibiotic(s)c Benzylpenicillin Amoxicillin ±an aminoglycoside

Second-choice antibiotic(s)c A tetracycline, or a cephalosporin Erythromycin ±an aminoglycoside

Gram-negative rods Enterobacteriaceae (coliform organisms) Escherichia coli, Enterobacter, Klebsiella Infections of urinary tract

Shigella (dysentery)

An oral cephalosporin, or a quinolone An aminoglycoside (intravenous) or cefuroxime A quinolone

Salmonella (typhoid, paratyphoid)

A quinolone or ceftriaxone

Haemophilus influenzae (infections of the respiratory tract, ear, sinuses; meningitis) Bordetella pertussis (whooping cough) Pasteurella multocida (wound infections, abscess) Vibrio cholerae (cholera) Legionella pneumophila (pneumonia, legionnaires disease) Helicobacter pylori (associated with peptic ulcer)

Ampicillin or cefuroxime

Septicaemia

Pseudomonas aeruginosa Urinary tract infection Other infections (of burns etc.)

A macrolide

Extended-spectrum penicillin Imipenem or a quinolone Ampicillin or trimethoprim Amoxicillin or chloramphenicol or trimethoprim Cefuroxime (not for meningitis) or chloramphenicol Ampicillin

Amoxicillin +clavulanic acid A tetracycline A macrolide ±rifampicin

Ampicillin

Metronidazole +amoxicillin +ranitidined (2-week regimen)

Clarithromycin +metronidazole

A quinolone

Antipseudomonal penicillins Imipenem ±an aminoglycoside, or ceftazidime

Antipseudomonal penicillins +tobramycine

A quinolone -

Micro-organism(s)b Brucella (brucellosis) Bacteroides fragilis Oropharyngeal infection Gastrointestinal infection Gram-negative anaerobic rods (other than B. fragilis) Campylobacter (diarrhoea) Spirochaetes Treponema (syphilis, yaws) Borrelia recurrentis (relapsing fever) Borrelia burgdorferi (Lyme disease) Leptospira (Weil's disease) Rickettsiae (typhus, tick-bite fever, Q fever, etc.) Mycoplasma pneumoniae Chlamydia (trachoma, psittacosis, urogenital infections) Actinomyces (abscesses) Pneumocystis (pneumonia, especially in AIDS patients) Nocardia (lung disease, brain abscess) a

First-choice antibiotic(s)c Doxycycline +rifampicin

Second-choice antibiotic(s)c -

Benzylpenicillin

Metronidazole or clindamycin Imipenem

Metronidazole , clindamycin Benzylpenicillin or metronidazole A macrolide or a quinolone Benzylpenicillin

A cephalosporin or clindamycin A tetracycline or gentamicin

A tetracycline

A macrolide or ceftriaxone Benzylpenicillin

A tetracycline

-

Benzylpenicillin A tetracycline

A tetracycline A quinolone

A tetracycline or a macrolide A tetracycline

Ciprofloxacin

Benzylpenicillin Co-trimoxazole (high dose)

A tetracycline Pentamidine or atovaquone or trimetrexate -

Co-trimoxazole

-

This table is not meant to be a definitive guide for clinical treatment but a general indication of the main antimicrobial actions and thus of the overall usefulness of commonly used antibiotics. For a more comprehensive list, see Laurence et al. (1997). b Only the main diseases caused by each organism are mentioned (in parentheses). c ± signifies that an agent is to be used with or without another agent; if agents are to be used concomitantly, a plus sign only is used. d An antiulcer drug, not an antibiotic (see Ch. 25). e Not in the same syringe.