The rate of spontaneous mutations that confer resistance to an individual drug are well known: 1 mutation for every 107 cell divisions for EMB, 1 for every 108 divisions for STM and INH, and 1 for every 1010 divisions for RMP.Patients with extensive pulmonary TB have approximately 1012 bacteria in their body, and therefore will probably be harboring approximately 105 EMB-resistant bacteria, 104 STM-resistant bacteria, 104 INH-resistant bacteria and 10² RMP-resistant bacteria. Resistance mutations appear spontaneously and independently, so the chances of them harbouring a bacterium that is spontaneously resistant to both INH and RMP is
1 in 108 × 1 in 1010 = 1 in 1018, and the chances of them harbouring a bacterium that is spontaneously resistant to all four drugs is 1 in 1033. This is, of course, an oversimplification, but it is a useful way of explaining combination therapy.There are other theoretical reasons for supporting combination therapy. The different drugs in the regimen have different modes of action. INH are bacteriocidal against replicating bacteria. EMB is bacteriostatic at low doses, but is used in TB treatment at higher, bactericidal doses. RMP is bacteriocidal and has a sterilizing effect. PZA is only weakly bactericidal, but is very effective against bacteria located in acidic environments, inside macrophages, or in areas of acute inflammation.All TB regimens in use were 18 months or longer until the appearance of rifampicin. In 1953, the standard UK regimen was 3SPH/15PH or 3SPH/15SH2. Between 1965 and 1970, EMB replaced PAS.
Malakoplakia (from Greek Malako "soft" + Plako "plaque") is a rare inflammatory condition which makes its presence known as a papule, plaque or ulceration that usually affects the genitourinary tract. : 274  However, it may also be associated with other bodily organs. It was initially described in the early 20th century as soft yellowish plaques found on the mucosa of the urinary bladder. Microscopically it is characterized by the presence of foamy histiocytes (called von Hansemann cells) with basophilic inclusions called Michaelis–Gutmann bodies. It usually involves gram-negative bacteria. Causes
Malakoplakia is thought to result from the insufficient killing of bacteria by macrophages. Therefore, the partially digested bacteria accumulate in macrophages and leads to a deposition of iron and calcium. The impairment of bactericidal activity manifests itself as the formation of an ulcer, plaque or papule. Malakoplakia is associated with patients with a history of immunosuppression due to lymphoma, diabetes mellitus, kidney transplantation, or because of long-term therapy with systemic corticosteroids. Diagnosis
As malakoplakia is a condition associated with chronic cystitis, it usually presents itself as a cystitis condition. The following investigations may help in making the diagnosis of malakoplakia:
Urinalysis which indicates presence of bacteria and white blood cells. Urine culture
Cystoscopic evaluation confirms presence of ulcer or papule. Biopsy to rule out other causes. The presence of large multinucleated malakoplakia giant cells with concretions called as Michaelis Gutman bodies on microscopy. Treatment
Treatments for malakoplakia include catheterizing the affected person  with full aseptic precautions.