In vitro Reducing Effect of Cloxacillin on Minimum Inhibitory Concentrations to Imipenem, Meropenem, Ceftazidime, and Cefepime in Carbapenem-resistant Pseudomonas aeruginosa Isolates.

Today, resistance to antibacterial agents is the most important problem facing public health. Pseudomonas aeruginosa is a common gram-negative bacterium and an important cause of nosocomial infections. Resistance to many antibiotics in strains of P. aeruginosa isolated from hospital settings such as cephalosporins and carbapenems have been recently reported. Therefore, the introduction of a new strategy to treat the infection of these organisms will be beneficial. In this study we determined the ability of cloxacillin to reduce Minimum Inhibitory Concentrations (MICs) of carbapenem-resistant P. aeruginosa to imipenem (IMI), meropenem (MEM), ceftazidime (CAZ), and cefepime (FEP). From 2015 to 2017, 61 non-duplicates of carbapenem-resistant P. aeruginosa were collected from clinical samples of hospitalized patients in Kerman, Iran. The MICs of the isolates to IMI, MEM, CAZ, and FEP with/without cloxacillin were determined by microbroth dilution method. The level of MIC of isolates to carbapenems (IMI and MEM) and cephalosporins (CAZ and FEP) ranged from 1-256 µg/mL and 4-1024 µg/mL alone and from 1-32 µg/mL and 1-512 µg/mL in combination with cloxacillin, respectively. The MIC showed a significant difference reduction after the addition of cloxacillin (P ≤ 0.05). Our results showed in vitro potentially of cloxacillin in reduction of MIC to IMI, MEM, CAZ, and FEP in multi-drug resistant P. aeruginosa, therefore combination of these antibiotics with cloxacillin could be beneficial for treatment of infections caused by multi-drug resistant P. aeruginosa.

Synthesis and antibacterial activity of nitroaryl thiadiazole-gatifloxacin hybrids.

A number of gatifloxacin analogues containing a nitroaryl-1,3,4-thiadiazole moiety attached to the piperazine ring at C-7 position were prepared and evaluated as antibacterial agents against a panel of gram-positive and gram-negative bacteria. Among synthesized compounds, nitrofuran analog 6a exhibited more potent inhibitory activity against gram-positive bacteria including Staphylococcus epidermidis (MIC=0.0078 microg/mL), Bacillus subtilis (MIC=0.0039 microg/mL), Enterococcus faecalis (MIC=0.125 microg/mL) and Micrococcus luteus (MIC=0.125 microg/mL), with respect to other synthesized compounds and reference drug gatifloxacin. The target compounds were also assessed for their cytotoxic activity against normal mouse fibroblast (NIH/3T3) cells using MTT assay. The results indicated that these compounds exhibit antibacterial activity at non-cytotoxic concentrations.