OBJECTIVETo study the in vitro antibacterial activity of meropenem combined with doxycycline, ciprofloxacin, sulbactam or cefoperazone/sulbactam against clinically isolated extensively drug-resistant Acinetobacter baumannii (XDRAB).

METHODSUsing a checker board synergy design, the minimal inhibitory concentration (MIC) of antibiotics against 50 isolates of XDRAB was determined by broth microdilution antifungal susceptibility test. The fractional inhibitory concentration (FIC) index was calculated to determine the combined effect of the antibiotics.

RESULTSMeropenem showed significantly reduced MIC50 and enhanced antimicrobial activities when combined with doxycycline, sulbactam or cefoperazone/sulbactam. The FIC results suggested that the main actions of doxycycline, sulbactam, and cefoperazone/sulbactam were synergistic (38%, 26%, and 10%, respectively) and addictive (62%, 74%, and 90%, respectively) without indifferent or antagonistic effects. The main actions of meropenem combined with ciprofloxacin were additive (56%) and indifference (44%) with synergistic and antagonistic effects.

CONCLUSIONMeropenem combined with doxycycline, sulbactam or cefoperazone/sulbactam shows excellent activity against clinical isolates of XDRAB.

Acinetobacter baumannii ; drug effects ; Anti-Bacterial Agents ; pharmacology ; Drug Combinations ; Drug Synergism ; Microbial Sensitivity Tests ; Thienamycins ; pharmacology

OBJECTIVE: To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis. METHODS: Biapenem/clavulanate (BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis (Mtb) multidrug-resistant (MDR) isolates, extensively drug-resistant (XDR) isolates, and the H37RV strain. BP/CL activity against the H37Rv strain was assessed in liquid cultures, in macrophages, and in mice.. RESULTS: BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units (CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment (isoniazid + rifampin + pyrazinamide) after 2 months of treatment. CONCLUSION BP/CL may provide a new option to clinically treat MDR tuberculosis.
Animals ; Anti-Infective Agents ; pharmacology ; therapeutic use ; Cell Line ; Drug Evaluation, Preclinical ; Macrophages ; Mice ; Mycobacterium tuberculosis ; drug effects ; Thienamycins ; pharmacology ; therapeutic use ; Tuberculosis, Multidrug-Resistant ; drug therapy

OBJECTIVETo analyze the distribution of Enterobacteriaceae isolated from West China Hospital, investigate the antibiotic resistance profile of Enterobacteriaceae with decreased susceptibility to carbapenems and explore the molecular mechanism.

METHODSForty-five Enterobacteriaceae strains resistant or with reduced susceptibility to carbapenems were isolated from patients in West China Hospital. The antimicrobial susceptibility and carbapenemase-producing phenotypes of the bacteria were examined and specific PCR were performed to determine the molecular mechanism.

RESULTSOf the 45 isolates, 17, 21 and 36 were resistant or intermediate strains to imipenem, meropenem and ertapenem, respectively. The majority of these isolates showed resistance to cephalosporins. The modified Hodge test resulted in the highest positivity rate (77.8%), followed by EDTA disc test (57.8%) and PBA disc test (22.2%). BlaTEM, blaSHV and blaCTX-M were detected in 60.0%, 53.3% and 15.6% of these strains with reduced susceptibility. The rate of strains carrying 2 or more genes was 44.4%, and the detection rate of blaIMP was 48.9%. BlaKPC was identified in 4 (8.9%) high-level resistant strains and confirmed to locate on the plasmid.

CONCLUSIONProduction of carbapenemase contributes to reduced susceptibility of carbapenems in Enterobacteriaceae. The presence of blaKPC, MBL and ESBL, and their possible combinations can be the main factor contributing to carbapenem resistance or reduced susceptibility in Enterobacteriaceae. The KPC-2 carbapenemase gene located on the plasmids we found in this study can cause potential horizontal transmission across strains.

Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Carbapenems ; pharmacology ; Cephalosporins ; pharmacology ; Enterobacteriaceae ; drug effects ; enzymology ; genetics ; Gene Amplification ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Polymerase Chain Reaction ; Thienamycins ; pharmacology ; beta-Lactam Resistance ; beta-Lactamases ; genetics ; metabolism ; beta-Lactams ; pharmacology

With the widespread emergence of antimicrobial resistance, combination regimens of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are recommended for empirical treatment of pneumococcal meningitis. To evaluate the therapeutic efficacy of meropenem (M), we compared various treatment regimens in arabbit model of meningitis caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at 24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr, but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem monotherapy may not be a suitable choice for PRSP meningitis, while combination of meropenem and vancomycin could be a possible alternative in the treatment of PRSP meningitis.
Animals ; Anti-Bacterial Agents/pharmacology ; Cerebrospinal Fluid ; Disease Models, Animal ; *Drug Resistance, Microbial ; Human ; Male ; Meningitis, Pneumococcal/*drug therapy ; Penicillins/*pharmacology ; Rabbits ; Streptococcus pneumoniae ; Support, Non-U.S. Gov't ; Thienamycins/*pharmacology ; Time Factors

OBJECTIVETo investigate the pathogen distribution and drug resistance in coal workers' pneumoconiosis associated with pneumonia and to provide a scientific basis for early guidance for rational clinical application of antibacterial agents.

METHODSSeventy-six patients with coal workers' pneumoconiosis associated with pneumonia who were admitted to our hospital from June 2011 to June 2014 were enrolled as subjects. The sputum specimens were aseptically collected for bacterial culture and drug sensitivity tests.

RESULTSIn 245 sputum specimens collected from 76 patients, a total of 218 strains of pathogens, including 163 strains of Gram-negative bacilli (74.77%), 39 strains of Gram-positive cocci (17.89%), and 16 strains of fungi (7.34%) were isolated by bacteriological tests. The main Gram-negative bacilli had high rates of resistance to amoxicillin/clavulanic acid, ampicillin, cotrimoxazole, cefotaxime, and aztreonam, and were sensitive to amikacin, imipenem, and meropenem. The main Gram-positive cocci had high rates of resistance to penicillin, erythromycin, amoxicillin/clavulanic acid, ampicillin, cefotaxime, and clindamycin, and were sensitive to vancomycin and teicoplanin.

CONCLUSIONThe main pathogens in these patients with coal workers' pneumoconiosis associated with pneumonia are Gram-negative bacilli, which are highly resistant to common clinically used antibacterial agents. The pathogen distribution and drug resistance should be well understood, and the antibacterial agents should be rationally selected according to the results of drug sensitivity tests.

Anthracosis ; microbiology ; Anti-Bacterial Agents ; pharmacology ; Coal Mining ; Drug Resistance, Bacterial ; Gram-Negative Bacteria ; drug effects ; Humans ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Occupational Exposure ; adverse effects ; Pneumonia ; microbiology ; Thienamycins ; pharmacology

No abstract available.
Aged ; Drug Resistance, Bacterial ; Humans ; Imipenem/pharmacology/therapeutic use ; Klebsiella Infections/diagnosis/drug therapy/*microbiology ; Klebsiella pneumoniae/drug effects/isolation & purification/*physiology ; Male ; Microbial Sensitivity Tests ; Phenotype ; Sepsis/diagnosis/drug therapy/*microbiology ; Thienamycins/pharmacology/therapeutic use

OBJECTIVETo investigate the mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii (CRAB) in burn patients and the antimicrobial activity of a combination of drugs against this bacteria in vitro.

METHODSA total of 135 strains of Acinetobacter baumannii (AB) from wound excretion, sputum, and venous catheter wall of patients hospitalized in our department from January 2011 to July 2013 were collected individually. Drug resistance of 135 strains of AB to 12 antibiotics commonly-used in clinic was detected using K-B paper diffusion method. Among the CRAB strains, double-disk synergy test was used to screen metallo-β-lactamase (MBL)-producing strains, and the drug resistance rates between MBL-producing strains and non-MBL-producing strains were compared. Minimal inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of cefoperazone/sulbactam, imipenem, cefepime, ampicillin/sulbactam, and amikacin used alone against MBL-producing CRAB were determined by broth microdilution method. MIC, MIC50, and MIC90 of amikacin respectively combined with imipenem, cefoperazone/sulbactam, cefepime, or ampicillin/sulbactam against MBL-producing CRAB were determined by checkerboard method with diluted agar. Fractional inhibitory concentration (FIC) index was calculated to determine the antibacterial effect of each combination of two antibiotics. Synergy with FIC lower than or equal to 0.5, or additivity with FIC higher than 0.5 and lower than or equal to 1.0 was regarded as effective, and indifference with FIC higher than 1.0 and lower than or equal to 2.0 or antagonism with FIC higher than 2.0 was regarded as ineffective. The effective rate was calculated. Data were processed with Chi-square test.

RESULTSThe resistant rates of the 135 strains of AB to imipenem, meropenem, and ceftazidime were high, and those of piperacillin/tazobactam and ampicillin/sulbactam were low. A total of 120 strains of CRAB was screened, accounting for 88.89%, among which the MBL-producing strains accounted for 78.33% (94/120). The resistant rates of MBL-producing strains to piperacillin/tazobactam, imipenem, meropenem, piperacillin, and cefepime were respectively 59.5%, 87.2%, 93.5%, 87.0%, 86.0%, and they were significantly higher than those of non-MBL-producing strains (respectively 43.0%, 81.3%, 87.5%, 78.4%, 64.0%, with χ(2) values from 4.571 to 8.260, P < 0.05 or P < 0.01). Among the inhibition concentrations of each of the 5 antibiotics used alone against MBL-producing strains, MIC, MIC50, and MIC90 of ampicillin/sulbactam were the lowest, respectively 4.00, 16, 64 µg/mL, while those of cefepime were high, respectively 32.00, 128, 512 µg/mL. MIC, MIC50, and MIC90 of amikacin combined with each of the other 4 antibiotics were decreased from 50.00% to 98.44% as compared with that of single administration of each antibiotic. Among the 94 strains of MBL-producing CRAB, the synergic, additive, indifferent, and antagonistic effects were respectively observed in 40, 33, 6, and 15 strains applied with combination of amikacin and ampicillin/sulbactam; 42, 30, 5, 17 strains applied with combination of amikacin and cefoperazone/sulbactam; 38, 15, 19, 22 strains applied with combination of amikacin and cefepime; 34, 2, 37, 21 strains applied with combination of amikacin and imipenem, among which the antibacterial effective rates decreased successively, respectively 77.7%, 76.6%, 56.4%, and 38.3%. The former two rates were respectively significantly higher than the latter two rates (with χ(2) values from 8.618 to 29.889, P values below 0.01).

CONCLUSIONSProduction of MBL is the main mechanism of resistance of the CRAB isolated from burn patients hospitalized in our department against carbapenems in about 3 years. The antibacterial effects of amikacin combined with each of the former-mentioned 4 agents are better than those of each of the five antibiotics used singly, and the effects are particularly obvious when combining amikacin with compound agent containing enzyme inhibitors.

Acinetobacter Infections ; drug therapy ; microbiology ; Acinetobacter baumannii ; drug effects ; isolation & purification ; Ampicillin ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Carbapenems ; pharmacology ; Cephalosporins ; pharmacology ; Drug Resistance ; Humans ; In Vitro Techniques ; Microbial Sensitivity Tests ; Penicillanic Acid ; analogs & derivatives ; pharmacology ; Pharmaceutical Preparations ; Piperacillin ; pharmacology ; Sulbactam ; pharmacology ; Thienamycins ; pharmacology ; beta-Lactamase Inhibitors ; pharmacology

BACKGROUND: Periodic monitoring of antimicrobial resistance trends of clinically important anaerobic bacteria such as Bacteroides fragilis group organisms is required. We determined the antimicrobial susceptibilities of clinical isolates of B. fragilis group organisms recovered from 2009 to 2012 in a tertiary-care hospital in Korea. METHODS: A total of 180 nonduplicate clinical isolates of B. fragilis group organisms were collected in a tertiary care hospital. The species were identified by conventional methods: the ATB 32A rapid identification system (bioMerieux, France) and the Vitek MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (bioMerieux). Antimicrobial susceptibility was determined by the CLSI agar dilution method. RESULTS: Imipenem and meropenem resistance rates were 0-6% for B. fragilis group isolates. The rate of resistance to piperacillin-tazobactam was 2% for B. fragilis and 0% for other Bacteroides species, but 17% for B. thetaiotaomicron isolates. High resistance rates to piperacillin (72% and 69%), cefotetan (89% and 58%), and clindamycin (83% and 69%) were observed for B. thetaiotaomicron and other Bacteroides spp. The moxifloxacin resistance rate was 27% for other Bacteroides spp. The MIC50 and MIC90 of tigecycline were 2-4 microg/mL and 8-16 microg/mL, respectively. No isolates were resistant to chloramphenicol or metronidazole. CONCLUSIONS: Imipenem, meropenem, chloramphenicol, and metronidazole remain active against B. fragilis group isolates. Moxifloxacin and tigecycline resistance rates are 2-27% and 8-15% for B. fragilis group isolates, respectively.
Anti-Infective Agents/*pharmacology ; Bacteroides Infections/*microbiology/pathology ; Bacteroides fragilis/*drug effects/isolation & purification ; Drug Resistance, Multiple, Bacterial ; Humans ; Imipenem/pharmacology ; Inhibitory Concentration 50 ; Microbial Sensitivity Tests ; Penicillanic Acid/analogs & derivatives/pharmacology ; Piperacillin/pharmacology ; Republic of Korea ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tertiary Care Centers ; Thienamycins/pharmacology

No abstract available.
Aged ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Cefotaxime/therapeutic use ; China ; Ciprofloxacin/therapeutic use ; Citrobacter freundii/drug effects/*enzymology/isolation & purification ; Drug Resistance, Multiple, Bacterial ; Humans ; Imipenem/pharmacology ; Male ; Microbial Sensitivity Tests ; Respiratory Tract Infections/*diagnosis/drug therapy/microbiology ; Thienamycins/pharmacology ; beta-Lactamases/*metabolism

Since its first isolation in 1997, vancomycin-intermediate Staphylococcus aureus (VISA) has been a clinical concern because it may lead to treatment failure. Up to the present, there were two reports of clinical VISA cases in Korea. We now report two additional cases of VISA with the minimum inhibitory concentration (MIC) of 4 microgram/mL. The first patient was a 59 yr-old man who had undergone total hip replacement arthroplasty in 1999 due to avascular necrosis of femur heads. He had recurrent episodes of infected hip caused by methicillin-resistant Staphylococcus aureus (MRSA) and was treated with vancomycin. He underwent replacement operation of prosthesis. Cultures of joint fluid and joint tissue grew S. aureus. Vancomycin MIC as determined by a broth microdilution method was 4 microgram/mL for the both isolates. The patient was treated with high enough doses of vancomycin to maintain serum trough concentrations at 20-25 microgram/mL for 52 days and was discharged. The second patient was a 57 yr-old man with diabetes. He lost consciousness from drinking. After recovery of consciousness, he was diagnosed with aspiration pneumonia. MRSA and Acinetobacter baumannii were cultured from sputum and the patient was treated with vancomycin and meropenem. During hospitalization, bed sores developed in his ankle and back. A wound culture from the sore grew S. aureus with vancomycin MIC of 4 microgram/mL. Since infection was localized, systemic antibiotics did not seem necessary, and the patient was transferred to another hospital for isolation and management.
Acinetobacter Infections/drug therapy ; Acinetobacter baumannii/isolation & purification ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Humans ; Joints/microbiology ; Male ; Methicillin-Resistant Staphylococcus aureus/*isolation & purification ; Microbial Sensitivity Tests ; Middle Aged ; Pressure Ulcer/microbiology ; Staphylococcal Infections/*drug therapy ; Thienamycins/pharmacology/therapeutic use ; Vancomycin/pharmacology/*therapeutic use ; *Vancomycin Resistance