meropenem and Candidiasis

In recent years, candidiasis attains major clinical importance due to its unique pathogenic strategy, which distinguishes it from other nosocomial infections. Secreted aspartyl proteinases (SAPs) is a hydrolytic enzyme secreted by Candida species that mediate versatile biological activity including hyphal formation, adherence, biofilm formation, phenotypic adaptation, etc. Emerging clinical evidence strongly suggested that conventional anti-fungal agent's are often prone to high level of resistance upon repeated exposure. Drug repurposing is an ideal strategy that shall impose the additional clinical benefits of the already approved molecules. Hence, through this realistic pathway, the potential of the suitable lead candidates will be explored in order to prolong the life span of existing molecules thereby need for newer therapeutics shall be avoided. The main aim of the present investigation is to determine the enzyme inhibitory potential of certain FDA-approved antibiotics and to validate its efficacy against the virulent enzyme secreted aspartyl proteinase (SAP) of Candida albicans via the AutoDock simulation program. The outcome of in silico dynamic simulations depicts that the drugs such as gentamicin, clindamycin, meropenem, metronidazole, and aztreonam emphasize superior binding affinity in terms of demonstrating considerable interaction with the core catalytic residues (Asp 32, Asp86, Asp 218, Gly220, Thr 221, and Thr 222). Data further indicates that the drug gentamicin exhibited best binding affinity of - 14.16 kcal/mol followed by meropenem (- 9.20 kcal/mol), clindamycin (- 9.00 kcal/mol), ciprofloxacin (- 8.95 kcal/mol), and imipenem (- 8.00 kcal/mol). In conclusion, repurposed antibiotics like gentamicin, clindamycin, meropenem, metronidazole, and aztreonam shall be considered an alternate drug of choice for the clinical management of drug resistant candida infections in the near future.

Topics: Anti-Bacterial Agents; Aspartic Acid Endopeptidases; Aspartic Acid Proteases; Aztreonam; Candida albicans; Candidiasis; Clindamycin; Drug Repositioning; Humans; Meropenem; Metronidazole

Within last 15 years, analyzing patterns of etiology and resistance in organisms causing neuroinfections, emergence of resistance has been observed in Slovakia in S. haemolyticus to teicoplanin (11%), Ps. aeruginosa and A. baumannii to meropenem (20%) and Candida spp. (non-albicans Candida spp.) to fluconazol (20%). There are no new antibiotics against carbapenem resistant Ps. aeruginosa and Acinetobacter baumannii.

Topics: Anti-Infective Agents; Brain Diseases; Candidiasis; Cross Infection; Drug Resistance, Microbial; Fluconazole; Humans; Meningitis; Meropenem; Pseudomonas Infections; Staphylococcal Infections; Teicoplanin; Thienamycins

Disseminated candidiasis is relatively common in immunocompromised patients. The treatment protocol of these patients usually includes broad-spectrum antibiotics and also emprical antifungals initiated due to unresponsiveness to antibiotics. In this study the efficacies of caspofungin and meropenem - separately and together - in mice with disseminated candidiasis were studied. Immunocompetent mice were infected intravenously with 2x10(6) CFU of Candida albicans. At 24 h postinfection, intraperitoneal therapy was initiated and was continued for 7 days. Therapy groups included those given caspofungin (0.5, 1.25, 5 mg/kg/day), meropenem (20 mg/kg/day), and a combination of the two drugs. The outcome of therapy was evaluated by kidney tissue burden studies and histologic examination. In vitro, drug susceptibilities were tested by checkerboard analysis. Kidney CFU counts showed that mice that had received both drugs had lower residual burdens. Caspofungin was effective at doses of 0.5, 1.25, 5 mg/kg compared to infected untreated controls. In vitro, MICs of caspofungin and meropenem were <0.075 micro g/ml and >64 micro g/ml, respectively. Synergism was observed with the combination. Histopathology showed that the degree of inflammation was 25% less and tubular necrosis was more restricted in combined therapy than monotherapy. The results indicate that concurrent caspofungin and meropenem therapy may be beneficial.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Candida albicans; Candidiasis; Caspofungin; Colony Count, Microbial; Drug Synergism; Drug Therapy, Combination; Echinocandins; Kidney; Lipopeptides; Male; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Peptides, Cyclic; Specific Pathogen-Free Organisms; Thienamycins

The incidence of candiduria is increasing in teaching hospitals. We examined the hypothesis that this trend was correlated with the amount of departmental antibiotic consumption. In the setting of a large teaching hospital in Israel, the correlation coefficient between departmental intravenous antibiotic consumption (expressed as daily defined dose (DDD)/1000 patient-days) and the incidence of candiduria per 1000 patient-days was 0.47 (P=0.03). For broad-spectrum antibiotics, the corresponding correlation coefficient was 0.66 (P=0.001). The strongest correlation with candiduria was shown for the use of meropenem (r=0.79, P<0.001) and ceftazidime (r=0.66, P=0.001). This is the first time that departmental habits of antibiotic use have been shown to be strongly correlated with the incidence of candiduria in hospitalized patients. These results add an important new dimension to the strategy of restricting broad-spectrum antibiotics.

Topics: Anti-Bacterial Agents; Candida; Candidiasis; Ceftazidime; Cross Infection; Drug Utilization; Hospital Bed Capacity, 500 and over; Hospital Departments; Hospitals, Teaching; Humans; Incidence; Infection Control; Infusions, Intravenous; Internal Medicine; Israel; Meropenem; Organizational Policy; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors; Surgery Department, Hospital; Thienamycins; Urinary Tract Infections