<prompt> ATT Drug that kills slowly or intermittently dividing bacteria:IsonizidRifampicinPyrazinamideStreptomycin  <response>: Ref: KDT 6th ed. pg. 740-44, Katzung Pharma 14th ed. pg. 845RIFAMPICIN It is a tuberculocidal agent of M. tuberculosis in addition to staph, aureus, pseudomonas, proteus, legionella etc. It has bactericidal action of which covers all subpopulations of TB bacilli, bat acts best on slowely or intermittently dividing ones as well as on many atypical mycobacteria. Both intracellular and extracellular bacilli are affected. MOA: It inhibits DNA dependent RNA synthesis Resistance of rifampicin is due to rpoB gene. Adverse effects: Hepatoxicity: MCMajor side effect Rifampicin imparts a harmless orange color to urine, sweat, tears, and contact lenses soft lenses may be permanently stained. Occasional adverse effects include rashes, thrombocytopenia, and nephritis. It may cause cholestatic jaundice and occasionally hepatitis and flu-like symptoms.ISONIAZID It is primarily tuberculocidal. Fast multiplying organisms are rapidly killed but quiescent ones are only inhibited. Acts on intracellular as well as extracellular TB bacilli and is equally active in acidic and alkaline medium. MOA: Inhibit synthesis of mycolic acid, which is a unique fatty acid component of mycobacterial cell wall. If given alone, resistance occurs in about 2-3 months Most common mechanism of INH resistance: Mutation of catalase-peroxidase gene Mutation of inh-A gene. Adverse effects: Isoniazid-induced hepatitis is the most common major toxic effect Peripheral neuropathy is observed in 10-20 of patients Neuropathy is due to a relative pyridoxine Vit B6 deficiency. Isoniazid promotes excretion of pyridoxine, and this toxicity is readily reversed by administration of pyridoxine. Central nervous system toxicity, which is less common, includes memory loss, psychosis, and seizures.PYRAZINAMIDE It is weakly tuberculocidal. PYZ is more lethal to intracellularly located bacilli and to those at sites showing an inflammatory response. MOA: Resembles that of INH. It inhibits mycolic acid synthesis but by interacting with a different fatty acid synthase encoding gene. Resistance of PYZ due to mutation in pncA gene. Adverse effects: Hepatotoxicity, nausea, vomiting, drug fever, and hyperuricemiaETHAMBUTOL Selectively tubecolostatic agent and clinically as active as streptomycin. Fast multiplying bacilli are more susceptible as are many atypical mycobacteria. MOA: Poorly understood, but it has been found to inhibit arabinosyl transferases involved in arabinogalactan synthesis and to interfere with mycolic acid incorporation in mycobacterial cell wall. Resistance of ethambutol due to alteration in the drug target gene- emb gene. Adverse effects: Retrobulbar neuritis, resulting in loss of visual acuity and red-green color blindness.STREPTOMYCIN Tuberculocidal agent, acts only on extracellular bacilli. It penetrates the tubercular cavities but doesnt crosses the CSF. Has poor action on acidic medium. Adverse effects: Ototoxic and nephrotoxic. Resistance is due to a point mutation in either the rpsL gene or rrs gene. 