meropenem and Tuberculosis--Pulmonary

Nocardia, a branching, filamentous bacteria, is widely distributed in the environment and can cause human infection in immune-compromised hosts. Inhalation of Nocardia leads to pulmonary disease. Microbiology laboratory processed the clinical samples from patients with respiratory infections. Smears were prepared from the samples and were stained and cultured. Five cases were positive for Nocardia. They were treated with the trimethoprim-sulfamethoxazole combination. The disease was cured in three patients, and two died due to other comorbid conditions leading to complications. Nocardiosis is encountered in parts of the world even where it is not endemic due to increased world travel. So physicians and laboratory staff should be aware of this and try to diagnose it. Early detection can lead to the prompt initiation of treatment and reduced mortality in these patients. Patients with disseminated or severe nocardiosis should be treated with combination therapy with two or more active agents.

Topics: Adult; Aged; Amikacin; Anti-Bacterial Agents; Cough; Diabetes Mellitus; Dyspnea; Female; Humans; Imipenem; Immunocompromised Host; India; Male; Meropenem; Middle Aged; Nocardia Infections; Pneumonia, Bacterial; Pulmonary Disease, Chronic Obstructive; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; 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

Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed.

Topics: Adolescent; Adult; Antitubercular Agents; Clavulanic Acid; Drug Therapy, Combination; Extensively Drug-Resistant Tuberculosis; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Mycobacterium tuberculosis; Salvage Therapy; Severity of Illness Index; Thienamycins; Treatment Outcome; Tuberculosis, Pulmonary; Young Adult

To screen effective useful drugs for disease due to M. abscessus, we determined MIC of 3 cephems [ceftazidime (CAZ), cefoxitin (CFX), flomoxef (FMOX)] and 3 carbapenems [imipenem (IPM), panipenem (PAPM), meropenem (MEPM)] for 8 strains of clinically isolated M. abscessus by micro-dilution method using MGIT system. In all the 8 strains, MICs of CAZ are higher than 32 micrograms/ml. MIC50, MIC90, MIC range of CFX are 32 micrograms/ml, > 32 micrograms/ml and 16- > 32 micrograms/ml respectively, and for FMOX, 16 micrograms/ml, 32 micrograms/ml and 16-32 micrograms/ml; for IPM, 8 micrograms/ml, 16 micrograms/ml and 8-16 micrograms/ml; for PAPM, 4 micrograms/ml, 16 micrograms/ml and 4-16 micrograms/ml; for MEPM, 8 micrograms/ml, 16 micrograms/ml and 8-16 micrograms/ml. From this study, it is concluded that FMOX, IPM, PAPM and MEPM can be clinically useful drugs in the treatment of the disease due to M. abscessus.

Topics: Carbapenems; Cefoxitin; Ceftazidime; Cephalosporins; Drug Resistance, Bacterial; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Thienamycins; Tuberculosis, Pulmonary