Activities of Biapenem against Mycobacterium tuberculosis in Macrophages and Mice / 生物医学与环境科学（英文）

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.

Pharmacokinetic and Pharmacodynamic Efficacies of Continuous versus Intermittent Administration of Meropenem in Patients with Severe Sepsis and Septic Shock: A Prospective Randomized Pilot Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The 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.</p><p><b>METHODS</b>Patients 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.</p><p><b>RESULTS</b>Clinical 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.</p><p><b>CONCLUSIONS</b>Continuous 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.</p>

Interaction between meropenem and valproate: Not to overlook

Background Valproic acid is commonly used to treat various types of seizures and follows nonlinear pharmacokinetics with a therapeutic range of 50 - 150 microg/ml. Several retrospective studies have reported that concomitant administration of VPA and carbapenem lead to decrease in VPA levels significantly and results in failure of seizure control. Different studies suggest the mechanism of interaction as [i] carbapenem may inhibit the gastrointestinal absorption of VPA [ii] meropenem accelerated the glucuronidation of VPA to VPA glucuronide [VPA-G] and inhibited the hydrolysis of VPA-G back to the VPA thus increasing the clearance of VPA and VPA-G and [iii] due to fast erythrocyte distribution of VPA by carbapenem, VPA levels has been reduced

Purpose To report four cases who "were maintained on therapeutic levels of VPA and had sub-therapeutic levels afterward due to the administration of meropenem

Method through CPOE system of AKUH the cases in 2014 were identified who were on valproate-meropenem combination with the available pre and post meropenem valproate levels

Result Patients of different age group showed significant reduction in VPA levels within 48 hour of administration of meropenem

Conclusion This case series describing the clinical importance of this probable drug interaction and promote its awareness among physicians in Pakistan. If a patient was therapeutic on the same dose of valproate and need broad spectrum coverage, a dose adjustment of valproate should not be done and physicians should consider either alternative broad spectrum antibiotic or renaly cleared antiepileptic to avoid this frequently used dangerous drug combination

Study on drug sensitivity against Comamonas testosteroni by Kirby-Bauer disk diffusion method / 中南大学学报(医学版)

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.

In vitro efficacy of meropenem, colistin and tigecycline against the extended spectrum beta-lactamase producing gram negative bacilli

To compare the in vitro efficacy of meropenem, colistin and tigecycline against extended spectrum Beta-lactamase producing Gram negative bacilli by minimal inhibitory concentration. Cross-sectional descriptive study. Department of Microbiology, Army Medical College, National University of Sciences and Technology, Rawalpindi, from June to December 2010. Routine clinical specimens were subjected to standard microbiological procedures and the isolates were identified to species level. Extended spectrum beta-lactamase producing Gram negative bacilli were detected by Jarlier disc synergy method and confirmed by ceftazidime and ceftazidime-clavulanate Etest. Minimum Inhibitory Concentration [MIC[90]] of meropenem, colistin and tigecycline was determined by Etest [AB BIOMERIUX] and the results were interpreted according to the manufacturer's instructions and Clinical and Laboratory Standards Institute guidelines and Food and Drug Authority recommendations. Results were analyzed by using Statistical Package for the Social Sciences version 20. A total of 52 non-duplicate extended spectrum Beta-lactamase-producing Gram negative bacilli were included in the study. The MIC[90] of tigecycline [0.75 microg/ml] was lowest as compared to the meropenem [2 microg/ml] and colistin [3 microg/ml]. Tigecycline is superior in efficacy against the extended spectrum Beta-lactamase producing Gram negative bacilli as compared to colistin and meropenem

Analysis of pathogen distribution and drug resistance in coal workers' pneumoconiosis associated with pneumonia / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Seventy-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.</p><p><b>RESULTS</b>In 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.</p><p><b>CONCLUSION</b>The 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.</p>

Antimicrobial Susceptibility of Clinical Isolates of Bacteroides fragilis Group Organisms Recovered from 2009 to 2012 in a Korean Hospital

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.

Prevalence of healthcare-associated infections among the pediatric patients admitted at Philippine General Hospital from the years 2011-2014

@#<p style="text-align: justify;"><strong>INTRODUCTION:</strong> 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%.</p> <p style="text-align: justify;"><strong>OBJECTIVES:</strong> 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.</p> <p style="text-align: justify;"><strong>METHODOLOGY:</strong> 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.</p> <p style="text-align: justify;"><strong>RESULTS:</strong> 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.</p> <p style="text-align: justify;"><strong>CONCLUSION:</strong> 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.</p>

Distribution and drug resistance of the pathogenic bacteria from sputum specimens of 1 125 children with tracheo bronchial foreign bodies / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To analyze the distribution and drug susceptibility of the pathogenic bacteria in the airway secretions in children with tracheobronchial foreign bodies so as to assist physicians in clinical prescription.</p><p><b>METHODS</b>Sputum specimens of 1 125 children with tracheobronchial foreign bodies were collected in removal of the foreign bodies by rigid bronchoscope, and the drug susceptibility test was performed.</p><p><b>RESULTS</b>Pathogenic bacteria were detected in 218 (19.4%) of 1 125 sputum specimens. Among the pathogenic bacteria, 126 (57.79%) strains were gram-negative bacilli, consisting of 76 (34.86%) strains of Haemophilus influenzae, 10 (4.59%) strains of Escherichia coli, 7 (3.21%) strains of Sewer enterobacter, 7 (3.21%) strains of Pseudomonas aeruginosa, and 6 (2.75%) strains of Klebsiella bacillus; and 92 (42.21%) strains were gram-positive bacilli, consisting of 80 (36.69%) strains of Streptococcus pneumonia and 10 (4.59%) strains of Escherichia coli. Most of detected gram-negative bacilli were highly sensitive to cefepime, ceftazidine, imipenem and amikacin, no strains were resistant to meropenem and ciprofloxacin. None of the detected gram-positive bacilli were resistant to cefepime, vancomycin, levofloxacin and teicoplanin.</p><p><b>CONCLUSIONS</b>The Haemophilus influenzae of gram-negative bacilli and the Streptococcus pneumonia of gram-positive bacilli are the main pathogenic bacteria existing in the airway secretions of children with tracheobronchial foreign bodies. The Haemophilus influenzae were highly sensitive to cephalosporin, imipenem and amikacin, and the Streptococcus pneumonia to cefepime, vancomycin, levofloxacin and teicoplanin.</p>

Infected tracheal diverticulum: a rare association with alpha-1 antitrypsin deficiency / Divertículo da traqueia infectado: um caso de associação rara com deficiência de alfa-1 antitripsina

Tracheal diverticulum, defined as a benign outpouching of the tracheal wall, is rarely diagnosed in clinical practice. It can be congenital or acquired in origin, and most cases are asymptomatic, typically being diagnosed postmortem. We report a case of a 69-year-old woman who was hospitalized after presenting with fever, fatigue, pleuritic chest pain, and a right neck mass complicated by dysphagia. Her medical history was significant: pulmonary emphysema (alpha-1 antitrypsin deficiency); bronchiectasis; and thyroidectomy. On physical examination, she presented diminished breath sounds and muffled heart sounds, with a systolic murmur. Laboratory tests revealed elevated inflammatory markers, a CT scan showed an air-filled, multilocular mass in the right tracheal wall, and magnetic resonance imaging confirmed the CT findings. Fiberoptic bronchoscopy failed to reveal any abnormalities. Nevertheless, the patient was diagnosed with tracheal diverticulum. The treatment approach was conservative, consisting mainly of antibiotics. After showing clinical improvement, the patient was discharged.

Divertículos da traqueia são evaginações benignas da parede traqueal e raramente diagnosticados na prática clínica. Podem ser congênitos ou adquiridos, e na maioria dos casos são assintomáticos, sendo tipicamente diagnosticados em estudos post-mortem. Relatamos o caso de uma mulher de 69 anos que foi hospitalizada após apresentar febre, fadiga, dor torácica pleurítica e uma massa cervical à direita complicada por disfagia. Tinha antecedentes pessoais de enfisema pulmonar (deficiência de alfa-1 antitripsina), bronquiectasias e tireoidectomia. Ao exame físico apresentava murmúrio vesicular diminuído, hipofonese cardíaca e um sopro sistólico. Laboratorialmente apresentava marcadores inflamatórios elevados, e uma TC mostrou uma massa aérea, multiloculada na parede direita da traqueia, achados confirmados por ressonância magnética nuclear. Realizou ainda uma fibrobroncoscopia que se revelou normal. Assumiu-se o diagnóstico de divertículo da traqueia. O tratamento proposto foi conservador, consistindo principalmente de antibioticoterapia. Após melhora clínica, a paciente recebeu alta.

Severe autogenously fecal peritonitis in ageing Wistar rats. Response to intravenous meropenem

PURPOSE: To evaluate the treatment outcome of severe peritonitis in rats with increasing age. METHODS: Thirty Wistar rats stratified in three groups: group I - six month-old; group II - 12 month-old; and group III - 18 month-old, underwent autogenously fecal peritonitis (6 ml/kg rat), and were treated with intravenous meropenem. The survival animals were followed-up for 45 days. The variables were expressed by their mean and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee. RESULTS: There was a significant increase in the mortality and morbidity in elderly rats. Of interest, even among young survival rats presenting with severe residual abscesses both in the abdomen and thorax cavities, they present an almost normal life. CONCLUSIONS: The treatment of severe autogenously fecal peritonitis with intravenous meropenem reached reasonable results in rats with six and twelve months of age, even considering residual abscesses on abdomen and thorax cavities. However, the great majority (80%) of elderly rats could not overcome the initial severe infectious challenge, proving that ageing is a very important risk factor for impairing immune response. Thus, sepsis remains a challenging situation, especially in elderly. .

Pharmacodynamic profiling of commonly prescribed antimicrobial drugs against Escherichia coli isolates from urinary tract

Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections. Minimum inhibitory concentration determination by Etest was performed for 205 Brazilian community urinary tract infection Escherichia coli strains from 2008 to 2012 and 74 E. coli bloodstream strains recovered from a surveillance study. Pharmacodynamic exposure was modeled via a 5000 subject Monte Carlo simulation. All isolates were susceptible to ertapenem and meropenem. Piperacillin/tazobactam, ceftriaxone and ciprofloxacin showed 100%, 97.5% and 83.3% susceptibility among outpatient isolates and 98.6%, 75.7% and 64.3% among inpatient isolates, respectively. Against outpatient isolates, all drugs except ciprofloxacin (82.7% in aggressive and 77.6% in conservative scenarios) achieved high cumulative fraction of response: car-bapenems and piperacillin/tazobactam cumulative fraction of responses were close to 100%, and ceftriaxone cumulative fraction of response was 97.5%. Similar results were observed against inpatients isolates for carbapenems (100%) and piperacillin/tazobactam (98.4%), whereas ceftriaxone achieved only 76.9% bactericidal cumulative fraction of response and ciprofloxacin 61.9% (aggressive scenario) and 56.7% (conservative scenario) respectively. Based on this model, standard doses of beta-lactams were predicted to deliver sufficient pharmacodynamic exposure for outpatients. However, ceftriaxone should be avoided for inpatients and ciprofloxacin empirical prescription should be avoided in both inpatients and outpatients with complicated urinary tract infection.

Combined drug sensitivity test of 50 strains of extensively drug-resistant Acinetobacter baumannii / 南方医科大学学报

<p><b>OBJECTIVE</b>To 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).</p><p><b>METHODS</b>Using 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.</p><p><b>RESULTS</b>Meropenem 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.</p><p><b>CONCLUSION</b>Meropenem combined with doxycycline, sulbactam or cefoperazone/sulbactam shows excellent activity against clinical isolates of XDRAB.</p>

Experimental study on concentrations and pharmacokinetics of antibiotics in bile and evaluation of their microbicidal potential / 中华外科杂志

<p><b>OBJECTIVE</b>To study the concentrations and pharmacokinetics of 6 different kinds of antibiotics in rabbit bile, and evaluate their microbicidal potential.</p><p><b>METHODS</b>Thirty-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)).</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSIONS</b>The 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.</p>

Mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii and the application of a combination of drugs in vitro / 中华烧伤杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSIONS</b>Production 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.</p>

Analysis of the carbapenemase-producing mechanism of Enterobacteriaceae with decreased susceptibility to carbapenems / 南方医科大学学报

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Forty-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.</p><p><b>RESULTS</b>Of 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.</p><p><b>CONCLUSION</b>Production 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.</p>

Extended Spectrum beta-lactamase-producing E. coli-related Nosocomial Peritonitis Treated Successfully with Meropenem in a Patient on Peritoneal Dialysis / 고신대학교의과대학학술지

Peritonitis is a common and potentially serious infection in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The most common organisms usually associated with CAPD peritonitis are Staphylococcus aureus and Staphylococcus epidermidis. Rarely, aerobic gram negative bacilli have been the causative agents of CAPD peritonitis. The treatment of CAPD peritonitis requires removal of the peritoneal catheter and treatment with parenteral antibiotics active against the causative pathogen. While hospitalized for CAPD peritonitis, a 55-year-old man on CAPD had nosocomial peritonitis secondary to infection by ESBL-producing E.coli, that was sensitive to imipenem and meropenem. He was treated successfully with a 4-week course of intraperitoneal meropenem therapy without subsequent relapse, loss of peritoneal catheter, ultrafiltration failure, or dialysis inadequacy.