amoxicillin-potassium-clavulanate-combination and Tuberculosis--Multidrug-Resistant

Interest in carbapenems has been rising in the last few years due to the emergence of drug resistant tuberculosis. Ertapenem (ETP), given once a day parenteral, and faropenem (FAR), oral, have a better administration profile than meropenem (MEM), imipenem (IPM) and doripenem (DOR). The addition of amoxicillin-clavulanate (AMC) inhibits the hydrolysis by the carbapenemase present in Mycobacterium tuberculosis (MTB). The aim of this study was to determine the in vitro activity of ETP and FAR against susceptible and resistant clinical MTB strains by two widely use methodologies, the BACTEC960 MGIT and microdilution.. 19 clinical isolates with different susceptibility profiles and H37Rv were included. Minimal inhibitory concentration (MIC) testing was performed using two methods of different concentrations of ETP and FAR with and without AMC. MIC50 was 2 and 8 for FAR with and without AMC by both methods. MIC90 was > 16 and > 8 by microdilution and MGIT respectively and did not change after AMC addition. 18/20 samples were resistant to the highest concentration of ETP, with and without AMC. Half of the samples had some susceptibility to FAR; addition of AMC further reduced the MIC level in seven isolates. 10/20 isolates showed susceptibility to FAR and the addition of AMC further reduced the MIC in 7 isolates. However, most of the MICs were near the limit of effectiveness (8 μg/mL). Resistance to FAR was associated with resistance to MEM (p = 0.04) but not to resistance profiles of other drugs, including M/XDR status.. The lack of ETP activity may be associated with its degradation, independent of carbapenemase, during incubation. No susceptibility pattern to traditional drugs can predict susceptibility to FAR and susceptibility testing is not routinely available. PK/PD studies are needed as reaching the concentrations tested in these experiments may be challenging. This work highlighted some of the limitations of carbapenem use. More evidence is needed to clarify their true impact in TB treatment and outcome, considering the financial burden, complications and microbiota changes associated with their use.

Topics: Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; beta-Lactams; Drug Resistance, Bacterial; Ertapenem; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Multidrug-Resistant

Topics: Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acid; Follow-Up Studies; Humans; Meropenem; Tuberculosis, Multidrug-Resistant

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Clavulanic Acid; Humans; Meropenem; Tuberculosis, Multidrug-Resistant

Topics: Amoxicillin-Potassium Clavulanate Combination; Extensively Drug-Resistant Tuberculosis; Fanconi Syndrome; Humans; Meropenem; Tuberculosis, Multidrug-Resistant

The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse.. We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively.. The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug.. Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation.

Topics: Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; beta-Lactamase Inhibitors; Clavulanic Acid; Clofazimine; Drug Discovery; Drug Resistance, Multiple, Bacterial; Humans; Leprostatic Agents; Meropenem; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Thienamycins; Tuberculosis, Multidrug-Resistant

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Animals; Coinfection; Drug Resistance; Female; Fever; Humans; Hypermastigia; Mycobacterium tuberculosis; Protozoan Infections; Tuberculosis, Multidrug-Resistant

Topics: Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; beta-Lactamase Inhibitors; beta-Lactams; Colony Count, Microbial; Drug Discovery; Humans; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant

Treatment of multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis resistant to both isoniazid and rifampicin, is challenging under the best of circumstances, and particularly in resource-limited settings. For patients who remain persistently sputum-culture-positive despite therapy with second-line TB drugs, treatment options are limited, especially if disease is too advanced for resective surgery. Salvage therapy refers to the design of a regimen combining new and previously used drugs in a final effort to attain sputum conversion before declaring treatment to have failed. We retrospectively evaluated the outcomes of salvage therapy in 213 Peruvian patients. Salvage regimens included a median of two new drugs (range 1-6) and nine (range 5-13) total (new plus previously used) drugs. The most frequently used new drug was moxifloxacin, followed by capreomycin, amoxicillin-clavulanate, kanamycin and clarithromycin. Culture conversion occurred in 65 (30.5%) patients. Salvage regimens that included moxifloxacin were significantly more likely to be followed by culture conversion (OR 2.2; p 0.02). Later-generation fluoroquinolones such as moxifloxacin should be used in salvage therapy but also in the initial treatment of MDR-TB, if the best clinical strategy is to use the most effective drugs when the patient has the best chance for cure. New TB drugs are most likely to be initially used in salvage patients, in conditions similar to those described here. Close bacteriological monitoring of these patients will be essential, as useful information about the best way to use these new drugs can be gained from analysis of salvage therapy cohorts.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Antitubercular Agents; Capreomycin; Clarithromycin; Drug Therapy, Combination; Female; Fluoroquinolones; Humans; Isoniazid; Kanamycin; Male; Moxifloxacin; Mycobacterium tuberculosis; Retrospective Studies; Rifampin; Salvage Therapy; Sputum; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Young Adult

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