Comparative in vitro activity of cefepime (BMY 28142) against multiresistant nosocomial isolates ofPseudomonas aeruginosa

The in vitro activity of a new parenteral cephalosporin cefepime (BMY 28142) was compared with that of ceftazidime, cefotaxime, piperacillin, imipenem, gentamicin, amikacin and ciprofloxacin against 173 recent multiresistantPseudomonas aeruginosa isolates of nosocomial origin using an agar dilution technique with an inoculum of 10⁴ CFU per spot. The activity of cefepime was comparable to that of ceftazidime, superior to that of cefotaxime, piperacillin, gentamicin and amikacin, but inferior to that of imipenem and ciprofloxacin. Cross-resistance ofPseudomonas aeruginosa to ceftazidime and cefepime occurred in nearly 50% of the cefepime resistant strains and 61.5% of the ceftazidime resistant strains respectively.     

Evaluation of VITEK 2 rapid identification and susceptibility testing system against gram-negative clinical isolates

A total of 281 strains of miscellaneous members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and other gram-negative bacteria were evaluated by use of identification tests with the VITEK 2 system (bioMérieux) and an API identification system (bioMérieux). A total of 237 (95%) strains were correctly identified to the species level. Only six (2.1%) strains were misidentified, and eight (2.8%) strains were not identified. Among 14 strains with discrepant identifications, 8 (57.1%) strains were nonfermenters. The susceptibilities of 228 strains to 11 antibiotics including amikacin, netilmicin, tobramycin, gentamicin, ciprofloxacin, imipenem, meropenem, ceftazidime, cefepime, piperacillin, and piperacillin in combination with tazobactam were tested with the VITEK 2 AST-No. 12 card and by the broth microdilution (MB) method, according to NCCLS guidelines, as a reference. For the 2,508 organism-antibiotic combinations, the rates at which duplicate MICs correlated within +/-1 dilution ranged from 84.2 to 95.6%. Only 13 (0.5%) and 10 (0.4%) of the susceptibility tests gave major errors (resistant with the VITEK 2 system but sensitive by the MB method) and very major errors (sensitive with the VITEK 2 system but resistant by the MB method), respectively. Both VITEK 2 ID-GNB (an identification system) and VITEK 2 AST-No. 12 (a susceptibility testing system) card systems gave rapid, reliable, and highly reproducible results.     

Evaluation of the VITEK 2 system for the identification and susceptibility testing of three species of nonfermenting gram-negative rods frequently isolated from clinical samples

VITEK 2 is a new automatic system for the identification and susceptibility testing of the most clinically important bacteria. In the present study 198 clinical isolates, including Pseudomonas aeruginosa (n = 146), Acinetobacter baumannii (n = 25), and Stenotrophomonas maltophilia (n = 27) were evaluated. Reference susceptibility testing of cefepime, cefotaxime, ceftazidime, ciprofloxacin, gentamicin, imipenem, meropenem, piperacillin, tobramycin, levofloxacin (only for P. aeruginosa), co-trimoxazole (only for S. maltophilia), and ampicillin-sulbactam and tetracycline (only for A. baumannii) was performed by microdilution (NCCLS guidelines). The VITEK 2 system correctly identified 91.6, 100, and 76% of P. aeruginosa, S. maltophilia, and A. baumannii isolates, respectively, within 3 h. The respective percentages of essential agreement (to within 1 twofold dilution) for P. aeruginosa and A. baumannii were 89.0 and 88.0% (cefepime), 91.1 and 100% (cefotaxime), 95.2 and 96.0% (ceftazidime), 98.6 and 100% (ciprofloxacin), 88.4 and 100% (gentamicin), 87.0 and 92.0% (imipenem), 85.0 and 88.0% (meropenem), 84.2 and 96.0% (piperacillin), and 97.3 and 80% (tobramycin). The essential agreement for levofloxacin against P. aeruginosa was 86.3%. The percentages of essential agreement for ampicillin-sulbactam and tetracycline against A. baumannii were 88.0 and 100%, respectively. Very major errors for P. aeruginosa (resistant by the reference method, susceptible with the VITEK 2 system [resistant to susceptible]) were noted for cefepime (0.7%), cefotaxime (0.7%), gentamicin (0.7%), imipenem (1.4%), levofloxacin (2.7%), and piperacillin (2.7%) and, for one strain of A. baumannii, for imipenem. Major errors (susceptible to resistant) were noted only for P. aeruginosa and cefepime (2.0%), ceftazidime (0.7%), and piperacillin (3.4%). Minor errors ranged from 0.0% for piperacillin to 22.6% for cefotaxime against P. aeruginosa and from 0.0% for piperacillin and ciprofloxacin to 20.0% for cefepime against A. baumannii. The VITEK 2 system provided co-trimoxazole MICs only for S. maltophilia; no very major or major errors were obtained for co-trimoxazole against this species. It is concluded that the VITEK 2 system allows the rapid identification of S. maltophilia and most P. aeruginosa and A. baumannii isolates. The VITEK 2 system can perform reliable susceptibility testing of many of the antimicrobial agents used against P. aeruginosa and A. baumannii. It would be desirable if new versions of the VITEK 2 software were able to determine MICs and the corresponding clinical categories of agents active against S. maltophilia.     

中国重症监护病房1994～2001年间不常见肠杆菌科细菌耐药监测

目的　调查近 7年全国 3 2家医院重症监护病房分离的 10 2 79株革兰阴性菌中 577株不常见的肠杆菌科细菌对 7种 β 内酰胺抗生素的耐药变迁。方法　 8年中共分离 577株产酸克雷伯菌、黏质沙雷菌、奇异变形杆菌、普通变形杆菌和摩根摩根菌。并分成 3组 :1994～ 1996年 ,1998～19 99年 ,2 0 0 0～ 2 0 0 1年。用Etest检测它们对下列 7种抗生素的最小抑菌浓度 (MIC) :包括亚胺培南(IPM)、头孢他啶 (CAZ)、头孢噻肟 (CTX)、头孢曲松 (CRO)、头孢哌酮 舒巴坦 (CSL)、哌拉西林 三唑巴坦 (PTZ)、头孢吡肟 (FEP)。按照美国临床实验标准委员会 2 0 0 3年标准指南 (NCCLSA10 0S 13 ) 〔10〕解释MIC值为耐药、中介和敏感 ,用WHONET 5.2软件分析数据。结果　这 5种不常见肠杆菌科细菌在2 0 0 1年所有分离菌株数中的排位是 :产酸克雷伯菌第 8位 ,敏感的抗生素 (即敏感率绝大多数年份 >80 % )依次为IPM、FEP、CAZ、TZP、CSL(10 0 %～ 83 .3 % )。黏质沙雷菌第 14位 ,敏感的抗生素依次为IPM、CAZ、TZP、CSL(10 0 %～ 87% )。奇异变形杆菌第 9位 ,敏感的抗生素依次为FEP、CAZ、IPM、TZP、CTX、CRO、CSL(10 0 %～ 83 .8% )。普通变形杆菌和摩根摩根菌分别为第 16位、17位 ,敏感的抗生素依次为CSL、IPM、FEP、TZP、CRO(1     

Low-dose β-lactam plus amikacin in febrile neutropenia: cefepime vs. piperacillin/tazobactam, a randomized trial

Patients with fever and granulocytopenia are at risk of developing severe infection. We performed a prospective, randomized trial to evaluate the efficacy of low-dose cefepime plus amikacin (C-A) compared to low-dose piperacillin/tazobactam plus amikacin (PT-A). Patients received cefepime (2 g/12 h) plus amikacin (15 mg/kg/day) or piperacillin/tazobactam (4 g/500 mg/8 h) plus amikacin. A total of 317 episodes of febrile granulocytopenia in 190 patients were studied (152 in the C-A group, 165 in the PT-A group). A microbiologically documented infection was present in 53 (35%) episodes in the C-A group and 41 (25%) episodes in the PT-A group (p = ns); a clinically documented infection was observed in 39 (26%) and 47 (28%) episodes, respectively. Toxicity was observed in 6 (4%) episodes in the C-A group and in 5 (3%) episodes in the PT-A group. The antibiotic success rate (no change or addition of antibiotics) was recorded in 89 (59%) and 105 (64%) cases, respectively (p = ns). Mortality related to infection was similar in each arm (3.9% vs. 3.6%). Combination therapy of low-dose β-lactam with an aminoglycoside achieves very good response rates and low rates of toxicity. It might be an attractive option in an environment of increasing resistance among gram-negative bacteria.     

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.     

Correlation of TEM, SHV and CTX-M extended-spectrum beta lactamases among Enterobacteriaceae with their in vitro antimicrobial susceptibility

Purpose: The present study was carried out to characterize the ESBL types and evaluated their in vitro activity against a collection of Gram negative bacteria (GNB) from a multicentric Indian surveillance study. Material and Methods: During January 2005 to June 2006, six tertiary care centres in India forwarded 778 non-duplicate GNB to our reference laboratory. Three hundred GNB from this collection were selected based on clinical significance and were used in the present study. Tested isolates included Escherichia coli (167), Klebsiella spp. (122) and Enterobacter spp. (11). ESBL screening and confirmation was performed for all the isolates. Minimum inhibitory concentration of imipenem, meropenem, ertapenem, levofloxacin, amikacin, piperacillin/tazobactam and ceftriaxone was determined by the E-test method. Molecular typing of the ESBLs was performed by polymerase chain reaction among the 121 selected isolates. Results: The study showed excellent susceptibility among the strains to imipenem (100%), meropenem (100%) and ertapenem (98.7%); good susceptibility to amikacin (89.7%) and piperacillin/tazobactam (85.3%) was observed. TEM and CTX-M were predominantly found in E. coli (39.2%) while, among the Klebsiella spp., TEM, SHV and CTX-M occurred together in 42.6% of the isolates. Conclusion: More than one ESBL was produced by many strains, and this was correlated with increased resistance levels. Carbapenems continue to show good in vitro activity and ertapenem is a potential alternative to imipenem and meropenem. Continued antimicrobial resistance surveillance is warranted in light of these findings.     

A survey of beta-lactam antibiotics and vancomycin dosing strategies in intensive care units and general wards in Belgian hospitals

Extended and continuous infusions with beta-lactam antibiotics have been suggested as a means of pharmacokinetic and pharmacodynamic optimisation of antimicrobial therapy. Vancomycin is also frequently administered in continuous infusion, although more for practical reasons. A survey was undertaken to investigate the recommendations by the local antibiotic management teams (AMTs) in Belgian acute hospitals concerning the administration (intermittent, extended or continuous infusion) and therapeutic drug monitoring of four beta-lactam antibiotics (ceftazidime, cefepime, piperacillin–tazobactam, meropenem) and vancomycin for adult patients with a normal kidney function. A structured questionnaire survey comprising three domains was developed and approved by the members of the Belgian Antibiotic Policy Coordination Committee (BAPCOC). The questionnaire was sent by e-mail to the official AMT correspondents of 105 Belgian hospitals, followed by two reminders. The response rate was 32 %, with 94 %, 59 %, 100 %, 100 % and 100 % of the participating Belgian hospitals using ceftazidime, cefepime, piperacillin–tazobactam, meropenem and vancomycin, respectively. Comparing intensive care unit (ICU) with non-ICU wards showed a higher implementation of extended or continuous infusions for ceftazidime (81 % vs. 41 %), cefepime (35 % vs. 10 %), piperacillin–tazobactam (38 % vs. 12 %), meropenem (68 % vs. 35 %) and vancomycin (79 % vs. 44 %) on the ICU wards. A majority of the hospitals recommended a loading dose prior to the first dose. For vancomycin, the loading dose and the trough target concentration were too low based on the current literature. This survey shows that extended and continuous infusions with beta-lactams and vancomycin are widely implemented in Belgian hospitals.     

Evaluation of the VITEK 2 system for rapid direct identification and susceptibility testing of gram-negative bacilli from positive blood cultures

This study explores the possibility of combining the BacT/Alert Microbial Detection System with the VITEK 2 system to achieve rapid bacterial identification and susceptibility testing. Direct inoculation of bacterial suspension to the VITEK 2 ID-GNB card and AST-NO09 card was made by differential centrifugation of blood cultures of organisms with gram-negative enteric bacillus-like morphology. A total of 118 strains were investigated; of these, 97 (82.2%) strains were correctly identified to the species level and 21 (17.8%) strains were not identified; by comparing the results with those of the reference method of API identification systems using a pure culture, it was found that no strain had been misidentified. Among the 21 strains with no identification, 13 (61.9%) strains were nonfermenters. The direct-identification reporting time of VITEK 2 was 3.3 h. Direct testing of susceptibility to 11 antibiotics, i.e., amikacin, cefepime, ceftazidime, ciprofloxacin, gentamicin, imipenem, meropenem, netilmicin, piperacillin, piperacillin-tazobactam, and tobramycin, was also performed by using the broth microdilution (MB) method according to the NCCLS guidelines as a reference. After comparing the MICs of the VITEK 2 system with those obtained by the MB method within +/-twofold dilution, it was determined that the 1,067 organism-antibiotic combinations had an overall correct rate of 97.6% (1,041 combinations). The rates of susceptibility to the 11 antibiotics ranged from 88.7 to 100%, respectively. Only two (0.2%) and four (0.4%) combinations of the susceptibility tests gave very major errors (i.e., reported as sensitive by the VITEK 2 system but shown to be resistant by the MB method) and major errors (i.e., reported as resistant by the VITEK 2 system but shown to be sensitive by the MB method), respectively. The reporting time for the direct testing of susceptibility against the 11 antibiotics for 97 blood culture isolates by the VITEK 2 system ranged from 3.3 to 17.5 h. Compared with conventional methods that require 1 or 2 days, this method can make same-day reporting possible and thus permit better patient management.     

Survey of the antibiotic sensitivity of Pseudomonas aeruginosa in France and the distribution of beta-lactam resistance mechanisms: the GERPB 1999 study

A prospective survey was carried out in october 1999 in 15 french teaching hospitals. Average susceptibility rates, determined by minimal inhibitory concentrations, for the 738 non-repetitive strains of P. aeruginosa isolated were: ticarcillin, 58%, ticarcillin + clavulanic acid, 56%, piperacillin, 73%, piperacillin + tazobactam, 82%, ceftazidime, 76%, cefepime, 53%, cefpirome, 36%, aztreonam, 58%, imipenem, 81%, amikacin, 62%, tobramycine, 71% and, ciprofloxacin, 60%. Among the 75% serotypable strains, the most frequent serotypes were: O:6 (15.3%), O:11 (14.5%), O:1 (10.4%), O:3 (7.9%), O:4 (6.1%) and O:12 (6.1%). The serotype O:12 was the most resistant to antibiotics. Forty-two percent of the strains were resistant or presented an intermediate susceptibility to ticarcillin. Mechanisms were as follow: 14.5% non enzymatic mechanism, 12.5% overproduction of the constitutive cephalosporinase, 7.1% transferable betalactamase and, 6.9% combination of these mechanisms. Among the 67 transferable betalactamases: 48 (71.6%) were PSE-1, 12 (19.4%) TEM-2 and 6 (7.5%) oxacillinases. One extended spectrum betalactamase was characterized. Among the cephalosporines tested, cefepime was less affected by the overproduction of constitutive cephalosporinase. Ceftazidime, remained the best cephalosporin except against the strains overexpressing the chromosomal type 1 beta-lactamase. Resistance to tobramycin was mainly due to enzymatic mechanisms with a high level of resistance. Decreased susceptibility was more frequent for amikacin than for tobramycin. This was probably related with non enzymatic mechanisms.     

Evolution of Resistance among Clinical Isolates of Acinetobacter over a 6-Year Period

 The aim of this report was to study the evolution of susceptibilities of 1532 clinical isolates of Acinetobacter recovered over a period of 6 years. The minimal inhibitory concentrations (MICs) of 15 antimicrobial agents were determined for all the isolates. The respective percentages of resistant strains in the years 1991 and 1996 were as follows: ciprofloxacin, 54.4% and 90.4%; tobramycin, 33% and 71.8%; amikacin, 21% and 83.7%; ampicillin plus sulbactam, 65.7% and 84.1%; ceftazidime, 57.4% and 86.8%; ticarcillin, 70% and 89.4%; trimethoprim plus sulfamethoxazole, 41.1% and 88.9%; and imipenem, 1.3% and 80%. The MIC90s of ciprofloxacin, sparfloxacin, biapenem, meropenem, imipenem, cefepime, cefpirome, and rifampicin against 250 imipenem-resistant Acinetobacter strains were >32, >32, 128, >256, 256, >256, 256, and 16 mg/l, respectively. With serious infections, it was necessary to resort to the use of colistin, the only antibiotic active in vitro.     

Piperacillin/Tazobactam Versus Cefotaxime Plus Metronidazole for Treatment of Children with Intra-Abdominal Infections Requiring Surgery

The efficacy of piperacillin/tazobactam at 100/12.5 mg/kg every 8 h (35 patients) was compared to cefotaxime plus metronidazole at 50/7.5 mg/kg every 8 h (35 patients) in 70 children with intra-abdominal infections requiring surgery. Diagnoses were gangrenous or perforated appendicitis (n=56), peritonitis (n=12), and abscess (n=2). Clinical cure was observed in 35 of 35 evaluable patients treated with piperacilin/tazobactam and in 34 of 34 evaluable patients treated with cefotaxime plus metronidazole. Presumed bacteriological eradication was noted in 29 of 30 evaluable patients in the piperacillin/tazobactam group and in 31 of 31 evaluable patients in the cefotaxime plus metronidazole group. In this study, piperacillin/tazobactam was as effective as cefotaxime plus metronidazole for treating children with intra-abdominal infections requiring surgery. Electronic Publication     

Correlation between sensitivity to fosfomycin and the presence of penicillinase PSE-1 in Pseudomonas aeruginosa

A prospective survey was carried out during three three-weeks periods in May, October 1997 and October 1998 in 13 teaching hospitals. All non-repetitive isolates of P. aeruginosa collected were subject to serotypage and determination of the inhibiting minimal concentrations for ticarcillin, piperacillin, piperacillin + tazobactam, ceftazidime, imipenem, amikacin, ciprofloxacin and fosfomycin. Identification of the betalactamases and quantification of the cephalosporinase were done for the strains intermediate or resistant to ticarcillin. The most frequent serotypes were O: 6 (17%), O: 11 (13%), O: 1 (10%) and O: 12 (9%). Serotype O: 12 was the least susceptible to antibiotics except for fosfomycin. Whatever the serotype, 76% of P. aeruginosa strains with bla PSE-1 are susceptible to fosfomycin, when only 29.8% of non bla PSE-1 producing strains were susceptible to this antibiotic. Integron encoding bla PSE-1 could be implicated in susceptibility to fosfomycin of P. aeruginosa strains. The associations fosfomycin + imipenem or fosfomycin + ceftazidime could be proposed in case of infections due to P. aeruginosa O: 12.     

Effect of β-lactam antibiotics on the in vitro development of resistance in Pseudomonas aeruginosa

Objective   To investigate whether stepwise selection of resistance mutations may mirror the continued bacterial exposure to antibiotics that occurs in the clinical setting.
Methods   We examined the in vitro development of resistance to a number of commonly used antibiotics (cefepime, cefpirome, ceftazidime, cefotaxime, piperacillin and imipenem) in Pseudomonas aeruginosa , a significant nosocomial pathogen. Stepwise resistance was assessed by serial passage of colonies located nearest to the inhibition zone on antibiotic-containing gradient plates.
Results   The lowest frequencies of spontaneous resistance mutations were found with cefepime and imipenem; these drugs also resulted in the slowest appearance of resistance of spontaneous resistance mutations. In five wild-type P. aeruginosa strains, cefepime-selected isolates required a mean of 30 passages to reach resistance; resistance occurred more rapidly in strains selected with other cephalosporins. P. aeruginosa strains that produced β -lactamase or non-enzymatic resistance generally developed resistance more rapidly than wild-type strains. For most strains, resistance to all antibiotics except imipenem correlated with increased levels of β -lactamase activity. Cross-resistance of cephalosporin-selected resistant mutants to other cephalosporins was common. Cephalosporin-resistant strains retained susceptibility to imipenem and ciprofloxacin.
Conclusions   From our in vitro study, we can conclude that the rate of development of resistance of P. aeruginosa is lower with cefepime compared with other cephalosporines.     

Comparative antibacterial activity of cefotaxime, ceftazidime and cefepime with regard to different strains of Enterobacter aerogenes selected for their resistance to third generation cephalosporins

After being confronted with the isolation in our laboratory of numerous antibiotic-multiresistant Enterobacter aerogenes strains, we studied the in vitro antimicrobial activity of cefotaxime, ceftazidime, and cefepime alone or in association with sulbactam. For that, we selected 67 isolates according to their low level of susceptibility to cefotaxime. First, we deduced from a synergy test in presence of clavulanic acid and cloxacillin the production of an extended spectrum beta-lactamase (ESBL) and/or an overproduction of a chromosomal cephalosporinase. Three groups of strains were thus defined: one group of ESBL strains, another group of overproducing strains of chromosomal cephalosporinase, and a last group that produced the two types of enzymes. Minimal inhibitory concentrations (MICs) of each cephalosporin alone or in presence of 8 mg/L of sulbactam, gentamicin or amikacin were measured. Our results demonstrated the best activity of cefepime: MICs were low with a value inferior to 4 mg/L independently of the type of beta-lactamase. They were lower than 0.5 mg/L in presence of sulbactam against ESBL-producing strains. The cephalosporins could be used in association with aminoglycosides according to their susceptibility.     

High frequency of antibiotic resistance among Gram-negative isolates in intensive care units at 10 Swedish hospitals

Objective: To investigate the resistance rates among Gram-negative isolates in Swedish intensive care units (ICUs).
Method: During 1994–95, members of the Swedish Study Group collected, on clinical indication, 502 consecutive initial isolates of Gram-negative bacteria from patients admitted to ICUs at 10 Swedish hospitals and performed minimal inhibitory concentration (MIC) determinations with the Etest. Breakpoints were defined according to the criteria of the Swedish Reference Group for Antibiotics (SRGA).
Results: The distribution of bacterial species was: Escherichia coli > Klebsiella spp. > Enterobacter spp. > Pseudomonas aeruginosa > Haemophilus spp. > Proteus spp. > Stenotrophomonas maltophilia > Citrobacter spp. > Acinetobacter > Pseudomonas. spp. > Morganella morganii > Serratia spp. Together these constituted 97% of all isolates. The frequencies of resistance for all the initial Gram-negative isolates were: ceftazidime 6.8%, cefotaxime 14.9%, ceftriaxone 18.5%, cefuroxime 44.1%, ciprofloxacin 4.2%, co-trimoxazole 17.8%, gentamicin 5.8%, imipenem 8.6%, piperacillin 20.2%, piperacillin/tazobactam 12.9% and tobramycin 5.8%.
Conclusions: Among Gram-negative isolates in Swedish ICUs, a very high frequency of resistance was seen to cefuroxime, and rather high frequencies of resistance to cefotaxime, ceftriaxone, piperacillin and piperacillin/tazobactam. These drugs cannot be recommended for further use as empirical monotherapy for severe ICU-acquired Gram-negative infections in ICUs in Sweden.     

Frequency of Occurrence and Antimicrobial Susceptibility of Bacterial Pathogens Associated with Skin and Soft Tissue Infections During 1997 from an International Surveillance Programme

 The SENTRY Antimicrobial Surveillance Programme was established to provide a coordinated, standardised, international surveillance on antimicrobial resistance. In one part of the programme, isolates from skin and soft tissue infections sent from 20 hospitals in 12 different European countries were investigated in the European coordinating centre. Of 1013 isolates, Staphylococcus aureus and Pseudomonas aeruginosa were the most significant species, constituting almost 50% of the referred isolates. Methicillin resistance in Staphylococcus aureus averaged 22% across Europe, only slightly less than that in isolates derived from blood. Less than 5% of the enterococcal isolates were resistant to vancomycin. Piperacillin/tazobactam was the most active penicillin-derived β-lactam compound against Pseudomonas aeruginosa, inhibiting 91.3% of the isolates, while ceftazidime and cefepime were the most active cephalosporins, inhibiting 85.8% and 80.3% of the isolates, respectively. Putative extended-spectrum β-lactamase production was not detected in Escherichia coli and was found in only 5.1% of the Klebsiella pneumoniae isolates. In general, strains of the family Enterobacteriaceae remained mostly susceptible to carbapenems, cefepime, and amikacin.     

Dactimicin,a new aminoglycoside: In vitro activity,post-antibiotic effect and interaction with other antibiotics

The in vitro activity of the new aminoglycoside dactimicin in comparison to amikacin was tested alone and in combination with piperacillin, mezlocillin and ceftazidime against freshly isolated clinical pathogens. Dactimicin was more active than amikacin againstEnterobacter cloacae, Providencia rettgeri and Salmonella spp., and less active than amikacin againstEscherichia coli, Pseudomonas aeruginosa andAcinetobacter anitratus. Using the checkerboard technique, the combination of either dactimicin or amikacin with the other drugs was shown to result in synergistic interaction against most of the 23 strains tested. Dactimicin-ceftazidime and amikacin-ceftazidime were the most effective combinations, demonstrating synergism against 91 % and 95 % of the isolates respectively. Antagonism was not encountered. Using the time-kill method, synergism was seen in most cases, indifference rarely being seen; antagonism was not observed. Dactimicin induced a post-antibiotic effect which ranged from 1 h forEnterobacter cloacae to 2.4 h forEscherichia coli. An average post-antibiotic effect of 0.6 h was also seen when dactimicin was combined with piperacillin, mezlocillin and ceftazidime. The findings indicate that dactimicin compares favorably in vitro with amikacin and suggest that clinical trials with this drug alone or in combination are warranted.     

In vitro activity of HR 810, a new broad-spectrum cephalosporin

HR 810, 3-〈(2,3-cyclopenteno-l -pyridinium)methyl〉-7-〈2-syn-methoximino-2-(2-aminothiazole-4-yl)-acetamido〉 ceph-3-em-4-carboxylate, is a new semisynthetic cephalosporin derivative. The in vitro activity of HR810 was compared with that of cefotaxime, ceftazidime, piperacillin and gentamicin using 368 strains of gram-negative and gram-positive bacteria. HR 810 was highly active againstEnterobacteriaceae, being the most active of the cephalosporins againstEnterobacter, Serratia andCitrobacter spp.; the MICs ranged from ≤0.06 to 8mg/l. The activity of HR 810 againstPseudomonas aeruginosa andAcinetobacter spp. was almost as good as that of ceftazidime. The new compound was superior to the other cephalosporins againstStaphylococcus aureus and inhibited allStreptococcus faecalis strains at a concentration of 16 mg/l.     

Strict anaerobic bacteria: comparative study of various beta-lactam antibiotics in combination with tazobactam or sulbactam]

The minimal inhibitory concentrations of piperacillin (PIP) or cefotaxime (CTX) alone or in combination with tazobactam (TAZ) were determined against 168 anaerobes. All the strains were inhibited by PIP + TAZ, but certain strains resistant to CTX + TAZ were found among B. fragilis, Eubacterium and Peptostreptococcus. The second investigations included 30 strains of Bacteroides fragilis. Concentrations of 2, 4 and 8 mg/l of TAZ and sulbactam (SUL) were combined with piperacillin or cefotaxime. The two beta-lactamase-inhibitors had similar activities when used at 2 or 4 mg/l, but at 8 mg/l TAZ was more active than SUL. All B. fragilis strains were inhibited by PIP + TAZ or PIP + SUL, whereas resistance was observed with CTX + SUL or CTX + TAZ. On the same strains the activities of 6 beta-lactams (PIP, mezlocillin, ticarcillin (TIC), CTX, ceftriaxone and ceftazidime) were determined in combination with either SUL 4 mg/l or TAZ 8 mg/l. Only PIP or TIC + SUL or TAZ were able to inhibit at least 90% of tested strains. No resistance could be detected with PIP + TAZ combination. As conclusion, the two inhibitors when combined with PIP or TIC offered greater activity against both Gram positive or negative anaerobes and PIP + TAZ remained the more potent combination.