amoxicillin-potassium-clavulanate-combination and Tuberculosis--Pulmonary

Topics: Adult; Aged; Amantadine; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cephalosporins; Cyclophosphamide; Drug Combinations; Erythromycin; Ethambutol; Humans; Metronidazole; Pyrazinamide; Respiratory Tract Diseases; Respiratory Tract Infections; Rifampin; Trimethoprim; Tuberculosis, Pulmonary

The early bactericidal activity (EBA) of an antituberculosis agent is the rate of decrease in viable colony-forming units (CFU) per milliliter of sputum during the first 2 d of treatment of patients with previously untreated smear-positive pulmonary tuberculosis. The objective of this open randomized study was to evaluate the EBA of the combination of amoxicillin 3 g and clavulanic acid 750 mg. Ten patients with a mean age of 34 y and a mean weight of 56 kg received amoxicillin/clavulanic acid and 5 patients with a mean age of 34 y and a mean weight of 57 kg received no drug. In the patients receiving 1 dose of amoxicillin/clavulanic acid daily for 2 d the mean log10CFU/ml of sputum before treatment was 6.7402 (SD 0.539) and after 2 d of treatment 6.7046 (SD 0.609); the corresponding values in patients receiving no drug were 6.7823 (SD 0.563) and 6.7502 (SD 0.673), respectively. The EBA of 0.018 (SD 0.130) in patients receiving amoxicillin/clavulanic acid did not differ significantly from that of 0.016 (SD 0.069) in patients receiving no drug. It is unlikely that the combination of amoxicillin/clavulanic acid has an important place in the treatment of tuberculosis with the exception of those patients with multidrug-resistant tuberculosis who are otherwise therapeutically destitute.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Blood Bactericidal Activity; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Sputum; Time Factors; Treatment Outcome; Tuberculosis, Pulmonary

Beta-lactams, in combination with beta-lactamase inhibitors, are reported to have activity against Mycobacterium tuberculosis bacteria growing in broth, as well as inside the human macrophage. We tested representative beta-lactams belonging to 3 different classes for activity against replicating M. tuberculosis in broth and nonreplicating M. tuberculosis under hypoxia, as well as against streptomycin-starved M. tuberculosis strain 18b (ss18b) in the presence or absence of clavulanate. Most of the combinations showed bactericidal activity against replicating M. tuberculosis, with up to 200-fold improvement in potency in the presence of clavulanate. None of the combinations, including those containing meropenem, imipenem, and faropenem, killed M. tuberculosis under hypoxia. However, faropenem- and meropenem-containing combinations killed strain ss18b moderately. We tested the bactericidal activities of meropenem-clavulanate and amoxicillin-clavulanate combinations in the acute and chronic aerosol infection models of tuberculosis in BALB/c mice. Based on pharmacokinetic/pharmacodynamic indexes reported for beta-lactams against other bacterial pathogens, a cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%TMIC) of 20 to 40% was achieved in mice using a suitable dosing regimen. Both combinations showed marginal reduction in lung CFU compared to the late controls in the acute model, whereas both were inactive in the chronic model.

Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; beta-Lactams; Clavulanic Acid; Disease Models, Animal; Drug Therapy, Combination; Female; Humans; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Streptomycin; Thienamycins; Treatment Outcome; Tuberculosis, Pulmonary

Pakistan is a high-burden country for tuberculosis (TB). The emergence and increasing incidence of extensively drug-resistant (XDR) TB has been reported in Pakistan. Similarly, the prevalence of multidrug-resistant TB infections with fluoroquinolone resistance (pre-XDR) is also increasing. To treat these infections, local drug susceptibility patterns of alternate antituberculosis agents, including levofloxacin (LVX), linezolid (LZD), and amoxicillin-clavulanate (AMC), is urgently needed. The aim of this study was to determine the susceptibility frequencies of drug-resistant (DR) Mycobacterium tuberculosis against LVX, LZD, and AMC. All susceptibilities were determined on Middlebrook 7H10 agar. A critical concentration was used for LVX (1 μg/ml), whereas MICs were determined for LZD and AMC. M. tuberculosis H37Rv was used as a control strain. A total of 102 M. tuberculosis isolates (XDR, n = 59; pre-XDR, n = 43) were tested. Resistance to LVX was observed in 91.2% (93/102). Using an MIC value of 0.5 μg/ml as a cutoff, resistance to LZD (MIC ≥ 1 μg/ml) was noted in 5.9% (6/102). Although the sensitivity breakpoints are not established for AMC, the MIC values were high (>16 μg/ml) in 97.1% (99/102). Our results demonstrate that LZD may be effective for the treatment of XDR and pre-XDR cases from Pakistan. High resistance rates against LVX in our study suggest the use of this drug with caution for DR-TB cases from this area. Drug susceptibility testing against LVX and AMC may be helpful in complicated and difficult-to-manage cases.

Topics: Acetamides; Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Humans; Levofloxacin; Linezolid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Ofloxacin; Oxazolidinones; Pakistan; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

To know the treatment outcome of patients with multidrug-resistant tuberculosis (MDR-TB) during gestation.. Retrospective study of 3 cases of pregnant women, who were treated for MDR-TB with a regimen including pyrazinamide, ethambutol, para-aminosalicylic acid, cycloserine and amoxicillin-clavulanic acid.. All patients showed a good response to anti-tuberculosis chemotherapy without any serious adverse effect, and were culture-negative at the time of delivery. Two patients delivered vaginally at weeks 40, and one patient delivered surgically at weeks 38. All newborns were healthy, and their tuberculin skin tests and placental tissue examinations were negative for tuberculosis.. MDR-TB can be successfully treated during pregnancy by using a regimen including effective second-line anti-tuberculosis drugs.

Topics: Adult; Aminosalicylic Acid; Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; Cycloserine; Drug Resistance, Multiple; Ethambutol; Female; Humans; Mutation; Mycobacterium tuberculosis; Parturition; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pyrazinamide; Retrospective Studies; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

A 67-year-old [correction of 53] man with multidrug resistant tuberculosis (MDR-TB) had been persistently positive for acid-fast bacilli (AFB) both on sputum smear and also on culture with the Ogawa egg medium for 30 years since 1951. The case had been treated previously with isoniazid, rifampin, streptomycin, ethambutol, kanamycin, ethionamide, paraaminosalicylate and cycloserine; however, M. tuberculosis strains isolated from this patient acquired a high resistance to all of these agents. Then, a new regimen of chemotherapy, INH combined with ofloxacin (OFLX) and amoxicillin-clavulanic acid (AMPC/ CVA), was applied to the case. He was successfully treated with this regimen, and a marked decrease in the amount of AFB on smear as well as on culture was observed during the course of chemotherapy. No adverse effects were seen meanwhile. These data suggest that it is worth while to try a regimen containing AMPC/CVA and OFLX in the treatment of MDR-TB.

Topics: Aged; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; Clavulanic Acids; Drug Administration Schedule; Drug Therapy, Combination; Humans; Isoniazid; Male; Ofloxacin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary