Drug susceptibility

Community-acquired methicillin-resistant S. aureus (CA-MRSA) is becoming an increasingly common pathogen in cellulitis. CA-MRSA can be distinguished from health care-associated MRSA (HA-MRSA) by its genetic dissimilarity, host population, drug susceptibility patterns, and toxin production. 

TABLE 72-3. Drug Regimens for Culture-Positive Pulmonary Tuberculosis Caused by Drug-Susceptible Organisms32... 

Effectiveness of TB therapy is determined by AFB smears and cultures. Sputum samples should be sent for AFB staining and microscopic examination (smears) every 1 to 2 weeks until two consecutive smears are negative. This provides early evidence of a response to treatment.28 Once on maintenance therapy, sputum cultures can be performed monthly until two consecutive cultures are negative, which generally occurs over 2 to 3 months. If sputum cultures continue to be positive after 2 months, drug susceptibility testing should be repeated, and serum concentrations of the drugs should be checked. 

Therapeutic drug monitoring (TDM) or applied pharmacokinetics is the use of serum drug concentrations to optimize therapy.28,36,37 Non-AIDS patients with drug-susceptible TB... 

Heifets LB. Drug susceptibility tests in the management of chemotherapy of tuberculosis. In Heifets LB, ed. Drug Susceptibility in the Chemotherapy of Mycobacterial Infections. Boca Raton, FL CRC Press 1991 89-122. 

The treatment of choice until susceptibility of the organism is known as the combination of vancomycin plus ceftriaxone. Penicillin may be used for drug-susceptible isolates with minimum inhibitory concentrations of 0.06 mcg/mL or less, but for intermediate isolates ceftriaxone is used, and for highly drug-resistant isolates a combination of ceftriaxone and vancomycin should be used. A high percent of S. pneumoniae is either intermediately or highly resistant to penicillin. 

Table 49-4 lists options for treatment of culture-positive pulmonary TB caused by drug-susceptible organisms. Doses of antituberculosis drugs are given in Table 49-5. The standard TB treatment regimen INH, RIF, pyrazinamide, and ethambutol for 2 months followed by INH and RIF for 4 months. 

The number of drugs susceptible to S-methylation is still limited but greater than the number turned over by COMT. Thiopurine methyl transferase (TPMT) is an important enzyme responsible for detoxifying mercaptopurine—a drug used to treat leukemia— as well as azathioprine —a prodrug that is metabolized to mercaptopurine (Fig. 7.12). This enzyme is polymorphic and patients who are homozygous for the deficient enzyme experience severe toxicity when given usual doses of mercaptopurine (19). Similar aromatic and heterocyclic sulfhydryls can also be substrates for TPMT. The similar thiol... 

Tuberculosis (TB) - The standard regimen for the treatment of drug-susceptible TB has been 2 months of INH, rifampin, and pyrazinamide followed by 4 months of... 

The current CDC recommendation for drug-susceptible initial treatment of active tuberculosis disease is a 6-month regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months. Treatment failure After treatment failure with other primary drugs in any form of active tuberculosis. 

Tuberculosis The standard regimen for the treatment of drug-susceptible tuberculosis has been 2 months of INH, rifampin, and pyrazinamide followed by 4 months of INH and rifampin (patients with concomitant infection with tuberculosis and HIV may require treatment for a longer period). When streptomycin is added to this regimen because of suspected or proven drug resistance, the recommended dosing for streptomycin is as follows ... 

The above recommendations apply to patients with drug-susceptible organisms. Patients with drug-resistant organisms may require longer duration treatment with other drug regimens. 

CDC recommendations Rifapentine may be used once weekly with isoniazid in the continuation phase of treatment for HIV-seronegative patients with noncavitary, drug-susceptible pulmonary tuberculosis who have negative sputum smears at completion of the initial phase of treatment. Continue this regimen for 4 months (total of 6 months of TB treatment). Have treatment for patients receiving isoniazid and rifapentine, and whose 2-month cultures are positive, extended by an additional 3 months (total of 9 months). 

Rifabutin appears as effective as rifampin in the treatment of drug-susceptible tuberculosis and is used in the treatment of latent tuberculosis infection either alone or in combination with pyrazinamide. Clinical use of rifabutin has increased in recent years, especially in the treatment of HIV infection. It is a less potent inducer of cytochrome 450 enzymes pathways than rifampin and results in less drug interaction with the protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Rifabutin is therefore commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients. Another important use of rifabutin in the HIV-infected population is prevention and treatment of disseminated MAC. 

Initial therapy in tuberculosis should include 4 drugs isonlazid, rifampin, pyrazina-mide, and ethambutol, until drug susceptibility results available... 

Anaerobic resistance was developed in both pathogenic species by prolonged cultivation of drug-susceptible strains or clones under increasing pressure of... 

Fig. 9 Comparison of steady-state concentrations of mRNA encoding PFOR and hy-drogenosomal malic enzyme in the drug-susceptible T. vaginalis strain TV 10-02 and its metronidazole-resistant derivatives with increasing level of resistance (see legend to Fig. 8). The amount of total RNA loaded onto each line was standardized according to the level of (1-tubulin. From Rasoloson et al. (2002) by courtesy of the Society of General Microbiology...

Fig. 10 Ultrastructure of hydrogenosomes of the T. foetus strain KV1-MR100 with fully developed metronidazole resistance (a,b) and of its drug-susceptible parent clone KV1 (c,d). Note the irregular shape, enlarged electron-dense core, and presence of tubular extensions (arrows) in hydrogenosomes of the drug-resistant strain. Bars 0.2 xm in a,b,c and 0.4 im in d. Original electron micrographs from the author (JK)...

Lossick JG, Muller M, Gorrell (1986) In vitro drug susceptibility and doses of metronidazole required for cure in cases of refractory vaginal trichomoniasis. J Infect Dis 153 948-955... 

Fallon, P.G., Mubarak, J.S., Fookes, R.E., Niang, M., Butterworth, A.E., Sturrock, R.F. and Doenhoff, M.J. (1997) Schistosoma mansoni maturation rate and drug susceptibility of different geographic isolates. Experimental Parasitology 86, 29-36. 

Standardized methods for surveillance of antifungal drug susceptibility have been a recent development (Rex et al, 1993). The M27 protocol of the National Committee for Clinical Laboratory Standards (NCCLS) for testing of yeasts focused on laboratory to laboratory reproducibility and became an approved standard in 1997 (National Committee for Clinical Laboratory Standards, 1997). A modification of M27 for testing of molds has recently been proposed as NCCLS document M38-P (National Committee for Clinical Laboratory Standards, 1998). With these tools, collaborative studies to validate the predictive power of these results have been possible. Interpretive breakpoints for... 

---