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

BACKGROUNDThe antibiotic meropenem is commonly administered in patients with severe sepsis and septic shock. We compared the pharmacokinetic, clinical, and bacteriological efficacies of continuous infusion of meropenem versus intermittent administration in such patients.

METHODSPatients admitted to the Intensive Care Unit (ICU) with severe sepsis or septic shock who received meropenem were randomly assigned to either the continuous (n = 25) or intermittent groups (n = 25). The continuous group received a loading dose of 0.5 g of meropenem followed by a continuous infusion of 3 g/day; the intermittent group received an initial dose of 1.5 g followed by 1 g for every 8 h. Clinical success, microbiological eradication, superinfection, ICU mortality, length of ICU stay, and duration of meropenem treatment were assessed. Serial plasma meropenem concentrations for the first and third dosing periods (steady state) were also measured.

RESULTSClinical success was similar in both the continuous (64%) and intermittent (56%) groups (P = 0.564); the rates of microbiological eradication and superinfection (81.8% vs. 66.7% [ P = 0.255] and 4% vs. 16% [ P = 0.157], respectively) showed improvement in the continuous group. The duration of meropenem treatment was significantly shorter in the continuous group (7.6 vs. 9.4 days; P= 0.035), where a better steady-state concentration was also achieved. Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first (Cmax: 19.8 mg/L vs. 51.8 mg/L, P= 0.000; Cmin: 11.2 mg/L vs. 0.5 mg/L, P= 0.000) and third dosing periods (Cmax: 12.5 mg/L vs. 46.4 mg/L, P= 0.000; Cmin: 11.4 mg/L vs. 0.6 mg/L, P= 0.000). For medium-susceptibility pathogens, continuous infusion concentrations above the minimal inhibitory concentration were 100%, which was better than that in the intermittent group.

CONCLUSIONSContinuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration. Continuous infusion may be more optimal against intermediate-susceptibility pathogens.

Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; pharmacokinetics ; therapeutic use ; Female ; Humans ; Intensive Care Units ; statistics & numerical data ; Male ; Middle Aged ; Pilot Projects ; Prospective Studies ; Sepsis ; blood ; drug therapy ; Shock, Septic ; blood ; drug therapy ; Thienamycins ; pharmacokinetics ; therapeutic use

OBJECTIVE: To determine the drug resistance of Comamonas testosteroni (C. testosteroni) by the Kirby-Bauer (K-B) method without Clinical and Laboratory Standards Institute (CLSI) explanation or the minimum inhibitory concentration (MIC) method with the standard CLSI explanation to evaluate the sensitivity of K-B method in detection of C. testosteroni.
 METHODS: K-B method and MIC method was used to determine the sensitivity of C. testosteroni to Piperacillin, Cefepime, Piperacillin/tazobactam, Imipenem, Meropenem, Amikacin, Gentamicin, Tobramycin, Ceftazidime and Ciprofloxacin. The interpretation standard for Pseudomonas aeruginosa was temporary used for the K-B method. The coincident rate was compared between the two methods.
 RESULTS: The complete or partial coincident rate for K-B method and MIC method to detect Piperacillin and Cefepime was 97.4% or 2.6%; the complete coincidence rate to detect Piperacillin/tazobactam, Imipenem and Meropenem was 100%; the complete or partial coincident rate to detect Amikacin, Gentamicin and Tobramycin 94.7% or 5.3%; the complete or partial coincident rate to detect Ceftazidime was 97.4% or 2.6%; the complete or partial coincident rate to detect Ciprofloxacin 86.8% or 10.6%, and the full non-coincidence rate was 2.6%.
 CONCLUSION The results of drug sensitive test from the two methods are highly consistent. We suggest that the microbiology labs do not report the interpretive results for C. testosteroni with K-B method but report the test results.
Anti-Bacterial Agents ; Cefepime ; Cephalosporins ; Comamonas testosteroni ; Imipenem ; Meropenem ; Microbial Sensitivity Tests ; Penicillanic Acid ; analogs & derivatives ; Piperacillin ; Piperacillin, Tazobactam Drug Combination ; Pseudomonas aeruginosa ; Thienamycins

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

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

INTRODUCTION: Healthcare associated infections (HAIs) continue to be a major public health concern throughout the world particularly in developing countries wherein prevalence rates range from 5.7%-19.1%.

OBJECTIVES: The aims of this study were to determine the prevalence of HAIs among pediatric patients admitted at Philippine General Hospital and to describe the trends of annual prevalence of HAIs in relation to infection control programs implemented.

METHODOLOGY: A retrospective study was conducted at the 145-bed capacity wards and intensive care units of the Department of Pediatrics, Philippine General Hospital (PGH) from January 2011 to December 2014 wherein HAI records from the database of the Section of Infectious and Tropical Disease in Pediatrics (INTROP) were reviewed. The following data were collected and encoded: (1) number of patients admitted in the different areas: Pediatric wards (Ward 9 and Ward 11), PICU and NICU; (2) number of patients who developed HAIs; and (3) microbial isolates, sites and antibiotic susceptibility results. Trends of yearly prevalence of HAIs in relation to infection programs implemented were determined, and the microbial isolates and their antibiotic sensitivity patterns were described.

RESULTS: Among 30,032 pediatric patients at risk for HAIs and admitted from January 2011 to December 2014, the prevalence of HAI was 11.37%. There was a decreasing trend in the yearly HAI rates from 2011 to 2014 which coincided with implementation of infection control programs and hiring of a part-time infection control nurse in 2012. The prevalence of HAIs was highest at the PICU (15.17%- 27.81%) followed by the two Pediatric wards, ward 9 (9.03%-19.87%) and ward 11(8.75%-14.76%) and lowest at the NICU (7.52%-9.44%). Top isolates were Pseudomonas putida, Pseudomonas aeruginosa, and Klebsiella pneumonia. Pseudomonas organisms were still sensitive to Ceftazidime, and Klebsiella to Meropenem.

CONCLUSION: The overall HAI prevalence during the 4-year study period was 11.37% (9.14% - 13.65%) comparable to those seen in developing countries. There was a decreasing trend of prevalence annually that coincided with the implementation of various infection control programs and the hiring of a part-time infection control nurse. The microbial isolates obtained vary per area but overall the same organisms were isolated during the study periods which were susceptible to the empiric treatment given.

Human ; Male ; Female ; Cross Infection ; Ceftazidime ; Pseudomonas Aeruginosa ; Meropenem ; Anti-bacterial Agents ; Pseudomonas Putida ; Klebsiella ; Intensive Care Units, Neonatal ; Infection Control ; Thienamycins

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

OBJECTIVETo study the concentrations and pharmacokinetics of 6 different kinds of antibiotics in rabbit bile, and evaluate their microbicidal potential.

METHODSThirty-six health rabbits were randomly divided into 6 groups, and each group was 6 rabbits. After anaesthesia, the common bile duct of rabbit was isolated and cumulated with a silicone tube. The rabbits were administered intravenously with the equal-effect dose of antibiotics. Bile (1.5 ml) was collected at different time points after administration, and the concentration of antibiotics of bile was assayed by high performance liquid chromatography. The bile drug concentration-time data were processed by software to figure out the pharmacokinetic parameters such as maximum concentration (C(max)), peak time (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of distribution (VD). The bile antibiotics concentration contrasted to the minimum inhibitory concentration (MIC), and attained the bactericidal index (C(max)/MIC) and the time when the drug concentration exceeded the MIC (T(>MIC)).

RESULTSThe C(max) and T1/2 of each antibiotic were as the followings: piperacillin (7 950 ± 3 023) mg/L and (1.97 ± 1.23) h, ceftriaxone (1 104 ± 248) mg/L and (3.14 ± 0.57) h, cefoperazone (5 215 ± 2 225) mg/L and (0.89 ± 0.13) h, meropenem (31.97 ± 12.44) mg/L and (0.36 ± 0.11) h, levofloxacin (66.3 ± 36.9) mg/L and (3.32 ± 2.57) h, metronidazole (28.2 ± 10.2) mg/L and (0.81 ± 0.33) h, respectively. Piperacillin/tazobactam and cefoperazone/sulbactam had the largest bactericidal index and the longest T(>MIC), and their bactericidal indexes were (62.1 ± 23.6) - (993.8 ± 377.9) and (164.8 ± 69.0) - (659.3 ± 275.9), their T(>MIC) were (6.00 ± 2.53) - (8.00 ± 0.00) h and (6.33 ± 1.97) - (8.00 ± 0.00) h. The bactericidal index and T(>MIC) of levofloxacin were the smallest, which were (2.1 ± 1.2) - (8.3 ± 4.6) and (0.54 ± 0.25) - (2.67 ± 1.03) h . Ceftriaxone and meropenem were as the medium, and their bactericidal indexes and T(>MIC) were (4.3 ± 1.0) - (69.2 ± 15.5) , (1.42 ± 0.65) - (8.00 ± 0.00) h and (2.0 ± 0.8) - (1 031.3 ± 401.4) , (0.29 ± 0.10) - (1.83 ± 0.26) h. The bactericidal index of metronidazole to anaerobic ranged from 7.4 to 294.9, and the T(>MIC) ranged from 1.88 to 5.00 h.

CONCLUSIONSThe bile concentrations of six antibiotics all exceed their effective bactericidal concentrations. The concentration-time curves of piperacillin, cefoperazone, meropenem and metronidazole conformed to one-compartment model, and ceftriaxone and levofloxacin are conformed to two-compartment model. Piperacillin/tazobactam and cefoperazone/sulbactam have the largest bactericidal index and the longest T(>MIC), so they can be chosen as the first choice for the therapy of hepatobiliary infection.For the anaerobic, the microbicidal potential of metronidazole is high.

Animals ; Anti-Bacterial Agents ; analysis ; pharmacokinetics ; Bile ; chemistry ; drug effects ; Cefoperazone ; analysis ; pharmacokinetics ; Drug Combinations ; Metronidazole ; analysis ; pharmacokinetics ; Microbial Sensitivity Tests ; Penicillanic Acid ; analogs & derivatives ; analysis ; pharmacokinetics ; Piperacillin ; analysis ; pharmacokinetics ; Rabbits ; Random Allocation ; Sulbactam ; analysis ; pharmacokinetics ; Thienamycins ; analysis ; pharmacokinetics

Acinetobacter Infections ; drug therapy ; Acinetobacter baumannii ; drug effects ; pathogenicity ; Adult ; Anti-Bacterial Agents ; administration & dosage ; therapeutic use ; Burns ; drug therapy ; microbiology ; Cefoperazone ; administration & dosage ; therapeutic use ; Humans ; Middle Aged ; Minocycline ; administration & dosage ; therapeutic use ; Retrospective Studies ; Sulbactam ; administration & dosage ; therapeutic use ; Thienamycins ; adverse effects ; therapeutic use ; Young Adult

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