P594 Intracellular killing of drug-resistant Staphylococcus aureus by different antibiotics

Objectives:  The aim of this study was to assess the carbapenem susceptibility of four nosocomial pathogens and to evaluate the reliability of the susceptibility results determined by E-test and disc diffusion (DD) methods.
Methods:  Escherichia coli ( n  = 73), Klebsiella pneumoniae ( n  = 60), Pseudomonas aeruginosa ( n  = 70) and Acinetobacter spp. ( n  = 70) isolated from nosocomial infections in 2002–2003 were included in the study. Thirty-five per cent of the strains were isolated from intensive care units. After determining antimicrobial susceptibility against imipenem and meropenem by DD (10  μ g; Oxoid, UK) and Etest (AB Biodisk, Solna, Sweden) methods, the results were categorised as susceptible (S), intermediate (I) and resistant (R) according to the NCCLS criteria. For statistical analyses, the intermediate group was included in the resistant category because of the low numbers of bacteria in the former group.
Results:  None of E. coli or K. pneumoniae strains were resistant to carbapenems, whereas, resistance reached up to 59.0% in Acinetobacter spp. and P. aeruginosa isolates. By either method, the pattern of the susceptibility of the four bacteria was not statistically significantly different for imipenem vs. meropenem. Total agreement of DD and E-test methods for susceptibility to imipenem was 95.7%, and 90.0% in Acinetobacter spp. and P. aeruginosa , respectively; and susceptibility to meropenem was 90.0% for both bacteria. However, the difference of the results obtained by either method was statistically significant for Acinetobacter spp.
Conclusion:  Study results suggest a high resistance rate for Acinetobacter spp. and P. aeruginosa strains against carbapenem antibiotics in our hospital. Further studies are needed to clarify whether E-test should be used to confirm meropenem resistance of Acinetobacter spp. determined by DD method.     

Oligonucleotide array-based identification of species in the Acinetobacter calcoaceticus-A. baumannii complex in isolates from blood cultures and antimicrobial susceptibility testing of the isolates

Acinetobacter calcoaceticus, A. baumannii, Acinetobacter genomic species (gen. sp.) 3, and Acinetobacter gen. sp. 13TU, which are included in the A. calcoaceticus-A. baumannii complex, are difficult to distinguish by phenotypic methods. An array with six oligonucleotide probes based on the 16S-23S rRNA gene intergenic spacer (ITS) region was developed to differentiate species in the A. calcoaceticus-A. baumannii complex. Validation of the array with a reference collection of 52 strains of the A. calcoaceticus-A. baumannii complex and 137 strains of other species resulted in an identification sensitivity and specificity of 100%. By using the array, the species distribution of 291 isolates of the A. calcoaceticus-A. baumannii complex from patients with bacteremia were determined to be A. baumannii (221 strains [75.9%]), Acinetobacter gen. sp. 3 (67 strains [23.0%]), Acinetobacter gen. sp. 13TU (2 strains [0.7%]), and unidentified Acinetobacter sp. (1 strain [0.3%]). The identification accuracy of the array for 12 randomly selected isolates from patients with bacteremia was further confirmed by sequence analyses of the ITS region and the 16S rRNA gene. Antimicrobial susceptibility testing of the 291 isolates from patients with bacteremia revealed that A. baumannii strains were less susceptible to antimicrobial agents than Acinetobacter gen. sp. 3. All Acinetobacter gen. sp. 3 strains were susceptible to ampicillin-sulbactam, imipenem, and meropenem; but only 67.4%, 90%, and 86% of the A. baumannii strains were susceptible to ampicillin-sulbactam, imipenem, and meropenem, respectively. The observed significant variations in antimicrobial susceptibility among different species in the A. calcoaceticus-A. baumannii complex emphasize that the differentiation of species within the complex is relevant from a clinical-epidemiological point of view.     

Antimicrobial activity of doripenem and other carbapenems against gram-negative pathogens from Korea

A total of 950 gram-negative bacterial isolates from patients with bacteremia and urinary tract infections were collected from tertiary-care hospitals in Korea. In vitro antimicrobial susceptibility testing was performed using broth microdilution test according to Clinical and Laboratory Standards Institute protocol. In general, carbapenems such as doripenem, imipenem, and meropenem were very active against Enterobacteriaceae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Acinetobacter sp. isolates. Doripenem was more potent than imipenem against most Enterobacteriaceae species except Proteus spp. based on minimum inhibitory concentration (MIC)(50) and MIC(90). In addition, doripenem displayed similar activity to meropenem but was superior to imipenem against ceftazidime-resistant Enterobacteriaceae isolates. For P. aeruginosa and Acinetobacter spp. isolates, MIC(50)s of doripenem were 1 and 0.5 mg/L, respectively, which were the same with those of meropenem but two- to fourfold lower than those of imipenem (both 2 mg/L). On the basis of the in vitro data, we conclude that doripenem has equivalent or more activity than other carbapenems such as imipenem and meropenem against most gram-negative pathogens from Korea. Thus, doripenem may be a promising new antimicrobial agent for the treatment of infections caused by gram-negative pathogens in Korea.     

Prospective, randomised, multicentre study of meropenem versus imipenem/cilastatin as empiric monotherapy in severe nosocomial infections

The clinical and bacteriological efficacy and the tolerability of meropenem versus imipenem/cilastatin (both 1 g t.i.d.) in severe nosocomial infections were compared in a multicentre, randomised, nonblinded study. A total of 151 patients were recruited; 133 (66 meropenem, 67 imipenem/cilastatin) were clinically evaluable and 84 (42 meropenem, 42 imipenem/cilastatin) bacteriologically evaluable. Most clinically evaluable patients (90%) were in intensive care units, required mechanical ventilation (72%), and had received previous antibiotic therapy (62%). The mean (±SD) APACHE II score was 15.2 (±6.6) in the meropenem group and 17.8 (±6.8) in the imipenem/cilastatin group. The primary infections were nosocomial lower respiratory tract infections (56% of patients), intra-abdominal infections (15%), septicaemia (21%), skin/skin structure infections (5%), and complicated urinary tract infections (3%); 35% of the patients had two or more infections. There was no significant difference between the meropenem and imipenem/cilastatin groups in the rates of satisfactory clinical (weighted percentage 87% vs. 74%) or bacteriological (weighted percentage 79% vs. 71%) response. There was a slightly higher rate of clinical success with meropenem against primary or secondary lower respiratory tract infection (89% vs. 76%). Drug-related adverse events occurred in 17% and 15% of meropenem and imipenem/cilastatin patients, respectively. Meropenem (1 g t.i.d.) was as efficacious as the same dose of imipenem/cilastatin in this setting, and both drugs were well tolerated.     

Emergence of resistant isolates ofAcinetobacter calcoaceticus-A. baumannii complex in a Spanish Hospital over a five-year period

Acinetobacter calcoaceticus-A. baumannii complex species have emerged as a relevant cause of nosocomial infection and colonization over the past 20 years, mainly in intensive care units. The aim of this study was to investigate the in vitro activity of 14 antimicrobial agents against 177 clinical isolates from patients admitted to a Spanish teaching hospital over a five-year period. Susceptibility rates of 99%, 99%, 97%, and 74% were obtained for imipenem, meropenem, ampicillin plus sulbactam, and amikacin, respectively. Increases in resistance were detected mainly for ticarcillin, piperacillin plus tazobactam, ceftazidime, amikacin, and ofloxacin. These results indicate that treatment of nosocomial infections due toAcinetobacter calcoaceticus-A. baumannii complex strains may be difficult.     

In vitro antimicrobial activity of "last-resort" antibiotics against unusual nonfermenting Gram-negative bacilli clinical isolates

In this prospective multicentric study, we assessed the in vitro antimicrobial activity of carbapenems (imipenem, meropenem, and doripenem), tigecycline, and colistin against 166 unusual nonfermenting Gram-negative bacilli (NF-GNB) clinical isolates collected from nine French hospitals during a 6-month period (from December 1, 2008, to May 31, 2009). All NF-GNB isolates were included, except those phenotypically identified as Pseudomonas aeruginosa or Acinetobacter baumannii. Minimal inhibitory concentrations (MICs) of antimicrobial agents were determined by using the E-test technique. The following microorganisms were identified: Stenotrophomonas maltophilia (n=72), Pseudomonas spp. (n=30), Achromobacter xylosoxidans (n=25), Acinetobacter spp. (n=18), Burkholderia cepacia complex (n=9), Alcaligenes faecalis (n=7), and Delftia spp. (n=5). All isolates of Acinetobacter spp., A. faecalis, and Delftia spp. were susceptible to the three carbapenems. Imipenem exhibited the lowest MICs against Pseudomonas spp., and meropenem, as compared with imipenem and doripenem, displayed an interesting antimicrobial activity against A. xylosoxidans and B. cepacia complex isolates. Conversely, no carbapenem exhibited any activity against S. maltophilia. Except for S. maltophilia isolates, tigecycline and colistin exhibited higher MICs than carbapenems, but covered most of the microorganisms tested in this study. To our knowledge, no prior study has compared antimicrobial activity of these five antibiotics, often considered as "last-resort" treatment options for resistant Gram-negative infections, against unusual NF-GNB clinical isolates. Further studies should be carried out to assess the potential clinical use of these antibiotics for the treatment of infections due to these microorganisms.     

Morphological changes induced by imipenem and meropenem at sub-inhibitory concentrations in Acinetobacter baumannii

Abstract Sub-inhibitory concentrations of imipenem and meropenem were evaluated for their ability to induce morphological changes with six strains of Acinetobacter baumannii isolated from patients with nosocomial pneumonia. Three strains were susceptible and three were resistant to carbapenems. The strains were grown in the presence of 0 (controls), 0.25x, 0.5x and 1x the MIC of both carbapenems for 4 h, and then examined after Gram's stain. Cells > or = 3 microm in size (spheroplasts) were considered to be altered. Both carbapenems induced significant numbers of spheroplasts compared to controls. Imipenem had more effect against susceptible strains, while meropenem had a greater effect against resistant strains.     

Carbapenem resistance mediated by Beta-lactamases in clinical isolates ofAcinetobacter baumannii in Spain

Four patients colonized/infected with carbapenem-resistant strains ofAcinetobacter baumannii are described. The first patient had a decubitus ulcer infection and had been on intravenous imipenem for 50 days. Two other patients, from whomAcinetobacter baumannii was isolated from urine, were hospitalized in the same ward as the first patient. The fourth patient had been mechanically ventilated in the intensive care unit for 4 month and had nosocomial pneumonia. He had been on intravenous meropenem for 1 month. Minimum inhibitory concentrations (MICs) of imipenem (128 mg/l) and meropenem (>128 mg/l) were the same for the isolates from the first three patients, and all of these isolates had the same repetitive extragenic palindromic polymerase chain reaction (rep-PCR) pattern. The MICs of carbapenems were lower for patient 4's isolate, which also had a different rep-PCR pattern. Beta-lactamases that hydrolyzed imipenem were detected in all four isolates; isoelectric points were 8.6–7.7 in the first three isolates and 6.8–7 in the fourth isolate.     

Imipenem resistance in nonfermenters causing nosocomial urinary tract infections

Nonfermenting gram-negative bacilli (nonfermenters) have emerged as important nosocomial pathogens causing opportunistic infections in immunocompromised hosts. These organisms show high level of resistance to b-lactam agents, fluoroquinolones and aminoglycosides. Imipenem is a carbapenem antibiotic, which can be very useful for treatment of infections caused by nonfermenters. Eighty-five nonfermenters causing nosocomial UTI were tested for MIC to imipenem by agar dilution method. Resistance to other antimicrobial agents was compared between imipenem sensitive (S) and resistance (R) groups. Overall 36.4% of nonfermenters were resistant to imipenem. Forty two percent of P. aeruginosa and 18.5% of Acinetobacter baumanii were imipenem resistant. Other nonfermenters showed variable resistance, resistance in Alcaligenes spp. being very high. More than 70% of the nonfermenters were resistant to ceftazidime, gentamicin and ciprofloxacin. Piperacillin and amikacin had the best in vitro susceptibility. No significant difference was found in the antibiotic susceptibility profile among imipenem sensitive (S) or resistant (R) strains.     

Virulence attributes in Brazilian clinical isolates of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen responsible for causing a huge variety of acute and chronic infections with significant levels of morbidity and mortality. Its success as a pathogen comes from its genetic/metabolic plasticity, intrinsic/acquired antimicrobial resistance, capacity to form biofilm and expression of numerous virulence factors. Herein, we have analyzed the genetic variability, antimicrobial susceptibility as well as the production of metallo-β-lactamases (MBLs) and virulence attributes (elastase, pyocyanin and biofilm) in 96 strains of P. aeruginosa isolated from different anatomical sites of patients attended at Brazilian hospitals. Our results revealed a great genetic variability, in which 86 distinct RAPD types (89.6% of polymorphisms) were detected. Regarding the susceptibility profile, 48 strains (50%) were resistant to the antimicrobials, as follows: 22.92% to the three tested antibiotics, 12.5% to both imipenem and meropenem, 11.46% to ceftazidime only, 2.08% to imipenem only and 1.04% to both ceftazidime and meropenem. Out of the 34 clinical strains of P. aeruginosa resistant to both imipenem and meropenem, 25 (73.53%) were MBL producers by phenotypic method while 12 (35.29%) were PCR positive for the MBL gene SPM-1. All P. aeruginosa strains produced pyocyanin, elastase and biofilm, although in different levels. Some associations were demonstrated among the susceptibility and/or production of these virulence traits with the anatomical site of strain isolation. For instance, almost all strains isolated from urine (85.71%) were resistant to the three antibiotics, while the vast majority of strains isolated from rectum (95%) and mouth (66.67%) were susceptible to all tested antibiotics. Urine isolates produced the highest pyocyanin concentration (20.15 ± 5.65 μg/ml), while strains isolated from pleural secretion and mouth produced elevated elastase activity (1441.43 ± 303.08 FAU) and biofilm formation (OD₅₉₀ 0.676 ± 0.32), respectively. Also, MBL-positive strains produced robust biofilm compared to MBL-negative strains. Collectively, the production of site-dependent virulence factors can be highlighted as potential therapeutic targets for the treatment of infections caused by heterogeneous and resistant strains of P. aeruginosa.     

Reevaluation of interpretive criteria for Haemophilus influenzae by using meropenem (10-microgram), imipenem (10-microgram), and ampicillin (2- and 10-microgram) disks.

A collection of 300 Haemophilus influenzae clinical strains was used to assess in vitro susceptibility to carbapenems (meropenem, imipenem) by MIC and disk diffusion methods and to compare disk diffusion test results with two potencies of ampicillin disks (2 and 10 micrograms). The isolates included ampicillin-susceptible or- intermediate (167 strains), beta-lactamase-positive (117 strains), and beta-lactamase-negative ampicillin-resistant (BLNAR; 16 strains) organisms. Disk diffusion testing was performed with 10-micrograms meropenem disks from two manufacturers. Meropenem was highly active against H. influenzae strains (MIC50, 0.06 microgram/ml; MIC90, 0.25 microgram/ml; MIC50 and MIC90, MICs at which 50 and 90%, respectively, of strains are inhibited) and was 8- to 16-fold more potent than imipenem (MIC50, 1 microgram/ml; MIC90, 2 micrograms/ml). Five non-imipenem-susceptible strains were identified (MIC, 8 micrograms/ml), but the disk diffusion test indicated susceptibility (zone diameters, 18 to 21 mm). MIC values of meropenem, doxycycline, ceftazidime, and ceftriaxone for BLNAR strains were two- to fourfold greater than those for other strains. The performance of both meropenem disks was comparable and considered acceptable. A single susceptible interpretive zone diameter of > or = 17 mm (MIC, < = or 4 micrograms/ml) was proposed for meropenem. Testing with the 2-micrograms ampicillin disk was preferred because of an excellent correlation between MIC values and zone diameters (r = 0.94) and superior interpretive accuracy with the susceptible criteria at > or = 17 mm (MIC, < or = 1 microgram/ml) and the resistant criteria at < or = 13 mm (MIC, > or = 4 micrograms/ml). Among the BLNAR strains tested, 81.3% were miscategorized as susceptible or intermediate when the 10-micrograms ampicillin disk was used, while the 2-micrograms disk produced only minor interpretive errors (12.5%). Use of these criteria for testing H. influenzae against meropenem and ampicillin should maximize reference test and standardized disk diffusion test performance with the Haemophilus Test Medium. The imipenem disk diffusion test appears compromised and should be used with caution for detecting strains for which imipenem MICs are elevated.     

2009—2011年某三甲医院鲍曼不动杆菌的耐药性分析

目的了解某三甲医院临床分离的鲍曼不动杆菌的分布及对各类抗菌药物的耐药性,以指导临床规范合理使用抗生素。方法收集常州市第一人民医院2009年1月至2011年12月临床分离的鲍曼不动杆菌,采用SPSS11．5统计软件统计分析鲍曼不动杆菌的检出率和耐药情况。结果2009—2011年共分离3360株鲍曼不动杆菌,均占全院分离病原菌的前三位。最常见的分离部位为下呼吸道,主要来源于ICU、呼吸内科、神经外科和神经内科,该菌对亚胺培南、美罗培南和哌拉西林-他唑巴坦的耐药率在2009年分别是55．52％、56．53％和70．01％,2011年分别上升至79．70％、77．61％和79．76％,差异有统计学意义。结论鲍曼不动杆菌对多种抗菌药物耐药率明显增高,泛耐药鲍曼不动杆菌比例明显增加。应加强耐药性监测,规范抗菌素的使用,防止鲍曼不动杆菌的暴发流行。     

Meropenem versus imipenem/cilastatin in the treatment of intraabdominal infections requiring surgery

In a prospective randomized study meropenem was compared with imipenem/cilastatin in the treatment of 62 patients with intraabdominal infections requiring surgery. The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gall-bladder disease. There were 30 patients in the meropenem group and 32 patients in the imipenem/cilastatin group. Both antibiotic regimens were given intravenously at a dosage of 1 g every 8 h for a mean duration of 7.7 days in the meropenem group versus 8.6 days in the imipenem/cilastatin group. Fifty-nine aerobic strains and 15 anaerobic strains were isolated from cultures of pus taken intraoperatively, the meropenem MICs ranging from 0.25 to 2 µg/ml. At follow-up at least one month after treatment the outcome was considered successful in all of 27 evaluable patients given meropenem and in all of 29 evaluable patients given imipenem/cilastatin. Both antibiotic regimens were well tolerated.     

Comparison of sensititre broth microdilution and agar dilution susceptibility testing techniques for meropenem to determine accuracy, reproducibility, and predictive values.

The stability, accuracy, reproducibility, and predictive value of Sensititre MIC panels containing meropenem (Merrem) were evaluated by using National Committee for Clinical Laboratory Standards (NCCLS)-recommended American Type Culture Collection (ATCC) strains and 110 selected strains of rapidly growing and fastidious aerobes and anaerobes with various degrees of susceptibility to meropenem. The NCCLS-recommended agar dilution method was used as a standard reference method. Meropenem-containing Sensititre MIC panels were monitored for their stabilities at room temperature and reproducibilities over 24 months by using six ATCC strains. Ninety-nine percent of the MICs of both meropenem and imipenem obtained for NCCLS-recommended ATCC strains were within the established ranges after 2 years. The overall agreement (+/- 1 twofold dilution) between the Sensititre and the agar dilution meropenem MICs was greater than 93%. The predictive value of meropenem MICs for indicating suspeptibility or resistance obtained by the Sensititre method was greater than 90%. No major or very major interpretive errors were observed, and only 5% of meropenem MICs were associated with minor interpretive errors. Problematic organisms were not observed. The Sensititre MIC panels containing meropenem offer a convenient and valid alternative to the NCCLS reference method for the susceptibility testing of potential pathogens likely to be recovered from mixed infections.     

Detection of metallo-β-lactamases producing Acinetobacter baumannii using microbiological assay,disc synergy test and PCR

Background: One leading factor responsible for resistance in Acinetobacter baumannii, an important opportunist in health care institutions globally, is the production of carbapenamases like metallo-β-lactamases (MBLs), which hydrolyze a variety of β-lactams including penicillin, cephalosporins and carbapenems. However, neither any standard guidelines are available nor any method has been found to be perfect for their detection. Various methods have shown discordant results, depending upon the employed methodology, β-lactamase substrate and MBL inhibitor used. This study aims to evaluate two phenotypic methods against PCR as gold standard among carbapenem resistant A. baumannii for identifying MBL producers. Materials and Methods: A total of 130 A. baumannii were screened for imipenem and meropenem resistance by Kirby–Bauer disc diffusion method. Phenotypic expression of MBL was detected by EDTA-imipenem-microbiological (EIM) assay and extended EDTA disc synergy (eEDS) test and presence of bla-IMP and bla-VIM was detected by PCR in all the carbapenem resistant isolates. Results: Of the 43 imipenem and/or meropenem resistant A. baumannii isolates, 4 (9.3%) were found to be MBL producers by EIM and 3 (6.97%) by eEDS. Only bla-VIM gene was detected in 7 (16.28%) by PCR. In addition EIM detected 14 (32.56%) carbapenem resistant non-metallo enzyme producers. Conclusion: Of the two MBL genes targeted, bla-VIM was only detected and that too in isolates resistant to both imipenem and meropenem. Further, EIM was useful in differentiating MBL from non-metalloenzymes producers.     

Comparative in vitro pharmacodynamics of BO-2727, meropenem and imipenem against Gram-positive and Gram-negative bacteria

Objective: To investigate and compare the in vitro pharmacodynamics of three carbapenems: imipenem, meropenem and BO-2727.
Method: The following studies were performed: (1) comparative studies of the rate of killing of the three carbapenems of reference strains of Gram-positive and Gram-negative bacteria at a concentration corresponding to the 1-h serum level following 500 mg intravenously in humans; (2) comparative studies of the rate of killing of BO-2727, meropenem and imipenem at different antibiotic concentrations of reference strains of Gram-positive and Gram-negative bacteria; (3) comparative studies of the rate of killing of BO-2727, meropenem and imipenem of bacteria which are phenotypically tolerant; (4) studies of the postantibiotic effect of BO-2727 using viable counts and optical density; (5) studies of the postantibiotic sub-MIC effect (PA SME) of BO-2727 using optical density.
Results: No difference in killing rate was noted between the three carbapenems, and there was no concentration-dependent killing of the Gram-negative strains after 6 h. A pronounced paradoxical effect was seen against Staphylococcus aureus. All three antibiotics were able to kill phenotypically tolerant bacteria. Only very short or no postantibiotic effect of BO-2727 was found against the investigated strains. Very long PA SMEs were noted for the Gram-negative strains, although there was a pronounced variation for the different strains of Pseudomonas aeruginosa.
Conclusions: There was no significant difference between the studied carbapenems in their pharmacodynamic properties. All three antibiotics acted similarly to other β-lactam antibiotics.     

Comparison of in vitro activities of levofloxacin, ciprofloxacin, ceftazidime, cefepime, imipenem, and piperacillin-tazobactam against aerobic bacterial pathogens from patients with nosocomial infections.

BACKGROUND AND PURPOSE: There is a rapid worldwide emergence of multidrug-resistant pathogens, especially in nosocomial isolates. This study compared the in vitro activities of levofloxacin, ciprofloxacin, ceftazidime, cefepime, imipenem, and piperacillin-tazobactam against 208 aerobic bacterial pathogens that caused 197 nosocomial infections in 184 patients. METHODS: Antimicrobial susceptibility was evaluated by E test in accordance with the guidelines of the National Committee for Clinical Laboratory Standards. RESULTS: Most (140/208, 67%) of the isolates were facultative Gram-negative bacilli. Levofloxacin and ciprofloxacin were the most effective (22/22, 100%) against oxacillin-sensitive Staphylococcus aureus. None of the antibiotics tested were found to be effective (0/25) against oxacillin-resistant S. aureus. Of the 11 isolates of Acinetobacter baumannii that were not pandrug-resistant (PDR), only 9 isolates (9/11, 81%) were sensitive to imipenem and 5 isolates (5/11, 45%) were sensitive to levofloxacin, ciprofloxacin, and ceftazidime. Another 22 isolates of A. baumannii that were PDR were completely resistant to all 6 antibiotics. The majority of isolates of Pseudomonas aeruginosa were sensitive to these 6 antimicrobial agents with 10/11 (91%) sensitive to levofloxacin and ciprofloxacin, 9/11 (83%) sensitive to ceftazidime, cefepime and piperacillin-tazobactam, and 8/11 (75%) sensitive to imipenem. CONCLUSIONS: The majority of the bacterial isolates causing nosocomial infections were found to be sensitive to the 6 antibiotics tested. Bacterial isolates of nosocomial infections that were completely resistant to these 6 antibiotics were PDR A. baumannii, PDR P. aeruginosa, and oxacillin-resistant S. aureus. More potent antimicrobial agents are needed to treat infections caused by PDR A. baumannii and PDR P. aeruginosa.     

Comparison of disk diffusion,Etest and VITEK2 for detection of carbapenemase‐producing Klebsiella pneumoniae with the EUCAST and CLSI breakpoint systems

The aim of this study was to compare CLSI and EUCAST MIC and disk diffusion carbapenem breakpoints for the detection of carbapenemase‐producing Klebsiella pneumoniae. K. pneumoniae strains with known KPC (n = 31) or VIM (n = 20) carbapenemases were characterized by disk diffusion (Oxoid) and Etest (bioMérieux) vs. imipenem, meropenem and ertapenem, and with VITEK2 (bioMérieux, five different cards). Extended‐spectrum β‐lactamase (ESBL) testing was performed with VITEK2 (bioMérieux), ESBL combination disks (Becton Dickinson) and the ESBL Etest (bioMérieux). With CLSI and EUCAST MIC breakpoints, respectively, 11 and seven of the strains were susceptible to imipenem, 12 and eight to meropenem, and seven and none to ertapenem. The EUCAST epidemiological cut‐off (ECOFF) values for meropenem and ertapenem identified all carbapenemase producers, whereas the imipenem ECOFF failed in five strains. All carbapenemase producers were detected with EUCAST disk diffusion breakpoints for ertapenem and meropenem, and four strains were susceptible to imipenem. CLSI disk diffusion breakpoints characterized 18 (imipenem), 14 (meropenem) and three (ertapenem) isolates as susceptible. When cards with a single carbapenem were used, detection failures with VITEK2 were four for imipenem, none for meropenem and one for ertapenem. Cards containing all three carbapenems had one to two failures. With ESBL combination disks, 21/31 KPC producers and 2/20 VIM producers were positive. With VITEK2, no VIM producers and between none and seven KPC producers were ESBL‐positive. All carbapenemase producers were detected with the meropenem MIC ECOFF, or the clinical EUCAST breakpoint for ertapenem. EUCAST disk diffusion breakpoints for meropenem and ertapenem detected all carbapenemase producers. VITEK2 had between none and four failures in detecting carbapenemase producers, depending on the antibiotic card.     

Tolerability of meropenem in children with IgE-mediated hypersensitivity to penicillins

Background:  Administration of meropenem to penicillin-allergic patients who might benefit from this treatment is usually avoided because of a 47.4% rate of cross-reactivity to imipenem, the prototype of the carbapenem class of β-lactam antibiotics, demonstrated in a single study on the basis of positive responses to skin tests with imipenem reagents. However, recent studies of ours have demonstrated a very low rate of cross-reactivity between penicillins and both meropenem and imipenem in adults.
Objective:  To assess cross-reactivity and tolerability of meropenem in children with documented penicillin allergy.
Methods:  One hundred and eight consecutive children who had suffered a total of 129 immediate reactions (120 urticarial and/or angioedematous manifestations and 9 anaphylactic shocks) to penicillins and had positive results to skin tests for at least one of the penicillin reagents tested underwent skin tests with meropenem and negative subjects were challenged with it.
Results:  One subject (0.9%) displayed a positive intradermal test to meropenem. The remaining 107 subjects with negative skin tests to meropenem tolerated challenges. Challenges were not followed by full therapeutic courses.
Conclusions:  Our results demonstrate a low rate of cross-reactivity between penicillins and meropenem. Therefore, the practice of avoiding meropenem in children with immunoglobulin E-mediated hypersensitivity could be abandoned; in those who especially require meropenem treatment, prophylactic skin tests are advisable, because negative results indicate tolerability.     

Antimicrobial activity of the new carbapenem biapenem compared to imipenem,meropenem and other broad-spectrum beta-lactam drugs

The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta-lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90 % of strains (MIC90) ofEnterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of theEnterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs againstPseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram-negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (includingBacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated forXanthomonas maltophilia, oxacillin-resistantStaphylococcus spp. andEnterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad-spectrum antibacterial agent for clinical use.