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Third generation cephalosporins are frequently used in the first-line treatment of Gram-negative rod (GNR) bacteremia but are unsuitable in the case of extended-spectrum-beta-lactamase-producing Enterobacterales (ESBL-E) or non-fermenting GNR infections. The aim of this study was to develop and evaluate a simple and rapid two-test protocol involving oxidase and β-Lacta tests performed directly on positive blood culture broth as a preliminary screen for non-fermenting or third generation cephalosporins-resistant GNR. The diagnostic performance of this approach was evaluated on 294 bottles for the oxidase test and 267 bottles for the β-Lacta Test. The sensitivity and specificity of the oxidase test were respectively 93.1% and 100%, and the sensitivity of the β-Lacta Test for ESBL-E was 100% and the specificity 99.5%. This simple protocol, which can be implemented in all laboratories and performed in only 20 min, may be a valuable tool to optimize first-line antibiotic therapy for bacteremia.

We examined the prevalence of various cephalosporins' resistance mechanisms in Acinetobacter baumannii clinical isolates. Phenotypic and molecular detection of Ambler classes A, B and D β-lactamases was performed on 75 isolates. Clonal relatedness was defined using Repetitive Extragenic Palindromic PCR. PCR mapping was used to examine the linkage of insertion sequences and the ampC gene, and ampC expression was analyzed by TaqMan reverse transcriptase-PCR. Twenty-six (37%) isolates carried at least one of the blaPER-1 or blaTEM-1. Sixty-nine (98.5%) out of 70 cephalosporin-resistant isolates had insertions upstream of the ampC gene, of which 48 (69%) and 6 (8%) were identified as ISAba1and ISAba125, respectively. Higher level of expression was obtained in resistant isolates lacking ISAba1/ampC combination in comparison with that in positive ones. The ability to up-regulate the expression of ampC gene in association with different insertion elements has become an important factor in A. baumannii resistance to cephalosporins.

From 2116 Klebsiella pneumoniae strains isolated between January 2001 and December 2002 in Nova Scotia, Canada, 25 (1.18%) showed a reduced susceptibility to cefoxitin or extended-spectrum cephalosporins. Narrow-spectrum β-lactamase genes ( bla SHV-11 , bla SHV-1 , bla SHV-26 , bla SHV-32 , bla SHV-36 , and bla SHV-40 ) were the most prevalent. Four new variants were identified ( bla LEN-17 , bla OKP-B-13 , bla OKP-B-14 , and bla OKP-A-11 ), representing the 1st description of bla OKP in the Americas. Among the extended-spectrum β-lactamase (ESBL) genes, bla SHV-2 , bla SHV2a , bla SHV-12 , and bla CTX-M-15 were detected (ESBL prevalence of 0.14%). Nineteen strains were resistant to cefoxitin (MIC, 32 to >256 μg/mL). Nevertheless, an AmpC-like activity was detected in only 1 strain, which expressed CMY-2. The combined effects of narrow-spectrum β-lactamase production and decreased or nonexpression of OmpK35/36 porins did not account for the cefoxitin resistance observed in some of these strains.

We report a pilot study comparing antimicrobial usage and antimicrobial resistance trends for prominent nosocomial pathogens between 1994-1996. A convenience sample of ten hospitals participated in this retrospective review. We found a large variation in antimicrobial use and resistance trends and that many hospitals did not have data readily available to evaluate drug usage and resistance rates. A significant strong positive correlation was observed between the usage of ceftazidime and the prevalence of ceftazidime resistant Pseudomonas aeruginosa (r = 0.8, p = 0.005) and of ceftazidime resistant Enterobacter species (r = 0.8, p = 0.02). The presence of antibiotic control policies correlated with lower rates of some resistant strains and less antibiotic use. Our findings can be a useful starting point for hospitals that want to systematically measure antimicrobial use and resistance. Hospital laboratories, pharmacies, and infection control departments must work together to develop databases that will facilitate such measurements.

Pseudomonas aeruginosa is an important nosocomial pathogen. Resistance to certain beta-lactam antimicrobial agents among P. aeruginosa is increasing. The SENTRY Antimicrobial Surveillance Program was designed to employ a network of hospitals in the United States, Canada, Latin America, and Europe to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY results was to extract information on the current North American susceptibility pattern of P. aeruginosa for two antipseudomonal cephalosporins, ceftazidime, and cefepime. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory by using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of the 34, 530 North American bacterial isolates tested during 1997 and 1998, 2299 (6.7%) were P. aeruginosa. There were no substantial differences in regional rates of P. aeruginosa susceptibility to ceftazidime (range 78.8-81.9%) or cefepime (range 80.0-83.4%) The percentage of resistant isolates among the 1784 United States isolates was 13.3% for ceftazidime versus 7.1% for cefepime (p0.05). It is essential to continue surveillance of the in vitro efficacy of these and other beta-lactam agents against P. aeruginosa because of the clinical importance of these safe and broad-spectrum cephems used alone or in combination in current clinical practice.

Previous studies have suggested that penicillin-resistant pneumococcal isolates (especially those with MIC >1 μg/mL) usually are clonally related. To test this hypothesis, the molecular epidemiology of 29 clinical isolates of penicillin-resistant pneumococci (of which 83% were also resistant to either cefotaxime or ceftriaxone) collected in central Taiwan was investigated by pulsed field gel electrophoresis. Twenty-seven distinct patterns were identified. Our results indicate that an increase in penicillin-resistant S. pneumoniae between April 1993 and June 1994 in central Taiwan is not due to the clonal dissemination of a limited number of epidemic strains.

Treatment of Enterobacter infection is complicated due to its intrinsic resistance to cephalosporins. Medical records of 192 adults with cancer who had Enterobacter bacteremia were analyzed retrospectively to evaluate the risk factors for and the treatment outcomes in extended-spectrum cephalosporin (ESC)-resistant Enterobacter bacteremia in adults with cancer. The main outcome measure was 30-day mortality. Of the 192 patients, 53 (27.6%) had bloodstream infections caused by ESC-resistant Enterobacter species. Recent use of a third-generation cephalosporin, older age, tumor progression at last evaluation, recent surgery, and nosocomial acquisition were associated with ESC-resistant Enterobacter bacteremia. The 30-day mortality rate was significantly higher in the resistant group. Multivariate analysis showed that respiratory tract infection, tumor progression, septic shock at presentation, Enterobacter aerogenes as the culprit pathogen, and diabetes mellitus were independent risk factors for mortality. ESC resistance was significantly associated with mortality in patients with E. aerogenes bacteremia, although not in the overall patient population.

The potency of cefepime, a parenteral aminothiazolyl methoxyimino cephalosporin, was assessed against 256 ceftazidime-resistant Gram-negative bacilli from five medical centers in the United States. In addition, cefepime activity was compared with that of ciprofloxacin and imipenem against 506 ceftazidime-resistant Gram-negative bacilli collected during an 11-medical-center international study. All US clinical isolates were susceptible (or = 8 micrograms/ml) to cefepime except Enterobacter cloacae (94% susceptible) and Pseudomonas aeruginosa (19% susceptible). Enterobacteriaceae isolates from the 11-nation sample were80% cefepime susceptible with the exception of those from Brazil (48% susceptible) and Italy (55% susceptible). These international, enteric isolates were also very susceptible to ciprofloxacin (55%-100% susceptible) and imipenem (84%-100% susceptible). Nonenteric organisms (Pseudomonas, Xanthomonas, and Acinetobacter) from the same international locations had overall rates of susceptibility of 47% for ciprofloxacin, 28% for imipenem, and only 5% for cefepime. Cross-resistance between the broad-spectrum cephalosporins (cefepime or ceftazidime) with either imipenem or ciprofloxacin was incomplete. Cefepime appears to have a spectrum of use against a significant number of contemporary, ceftazidime-resistant Gram-negative bacillus isolates worldwide.

Of 176 Salmonella isolates isolated from 2000 to 2003 in a Korean university hospital, 2 cefoxitin-resistant isolates of Salmonella enterica serovar Rissen were found in 2002. Both isolates were resistant to multiple β-lactam antibiotics, including ampicillin, amoxicillin-clavulanate, cefoxitin, cefotaxime, and ceftazidime. Cell sonicates of the both clinical isolates and their transconjugants had β-lactamase band of approximate isoelectric point of >8.6. The resistance to cefoxitin was transferred by conjugation to the recipient Escherichia coli J53. The resistance determinant was on conjugative plasmids that encoded a CMY-2, a plasmid-mediated AmpC β-lactamase. To our knowledge, these are the first description of S. enterica serovar Rissen harboring CMY-2 in South Korea.

A large international collection of Streptococcus pneumoniae (21 605 strains) was analyzed to determine the comparative activity of selected oral (cefuroxime and cefpodoxime) and parenteral (ceftriaxone and cefepime) cephalosporins when tested against different antimicrobial resistance phenotypes including penicillin-resistant strains and strains displaying additional resistances to other agents (erythromycin, clindamycin, tetracycline, and trimethoprim/sulfamethoxazole). The multidrug-resistant (MDR) rate ranged from 17.6% (penicillin- and erythromycin-resistant only) to 5.7% (resistance to all 5 drugs). The parenteral cephalosporins retained wider activity for all MDR phenotypes studied with the resistance rates (minimum inhibitory concentration ≥4 μg/mL) being lower for cefepime (1.3–1.9%) when compared with ceftriaxone (3.0–4.4%) or the orally administered cephalosporins, cefpodoxime (64.4–74.1%), and cefuroxime (69.3–79.1%). Our findings confirm that the parenteral cephalosporins, cefepime, and ceftriaxone possess significant activity against those MDR pneumococci responsible for an increasing number of serious respiratory tract infections.

In vitro cefditoren antimicrobial activity was tested by broth microdilution and disk diffusion methods against 300 Streptococcus pneumoniae and 299 Haemophilus influenzae isolates. MICs were also determined for three comparison drugs. The MICs of cefditoren were very comparable to those of cefotaxime against both species. If penicillin-resistant pneumococci are to be considered not susceptible to cefditoren, the tentative MIC breakpoints for cefditoren ofor = 0.25 microg/ml for susceptible andor 1.0 microg/ml for resistant could be selected. With these breakpoints, all penicillin-susceptible pneumococci were cefditoren-susceptible, as were 85% of penicillin-intermediate strains. Provisional zone diameter breakpoints would beor = 26 mm for susceptible andor = 20 mm for resistant. If penicillin-resistant pneumococcal infections are shown to clinically respond to cefditoren therapy, then a susceptible MIC breakpoint ofor = 1.0 microg/ml would be appropriate, with a corresponding zone diameter breakpoint ofor = 21 mm. A susceptible MIC breakpoint ofor = 0.5 oror = 1.0 microg/ml is appropriate for H. influenzae, but lack of correlation between cefditoren MICs and disk diffusion zone diameters when testing H. influenzae leads us to make no recommendations at this time regarding cefditoren disk tests for H. influenzae.

MICs of penicillin G and other drugs and serotypes were determined for 218 strains of Streptococcus pneumoniae isolated from children in southwestern Japan. Twenty-one (9.6%) and 81 (37.2%) isolates were penicillin-resistant (MIC/=2.0 microg/ml) and intermediate (MIC 0.13-1.0 microg/ml), respectively. Panipenem was most active parenteral agent against penicillin-intermediate (MIC(90) 0.125 microg/ml) and -resistant strains (MIC(90) 0.25 microg/ml). Among oral beta-lactam agents, cefditoren had good activity against penicillin-intermediate and resistant strains (MIC(90) 0.5/1.0 microg/ml). Serogroup 6 was the most prevalent (65/218) among all strains and 19F (44 strains) was the most prevalent among penicillin-intermediate and -resistant strains. Both pbp2b resistant and susceptible genes were found in penicillin-intermediate strains. Pbp2x resistant genes were found in 33 of 80 (41.3%) cefotaxime-susceptible strains. These results suggest that possible resistance mechanisms may occur even in drug susceptible strains and that drug susceptibility survey should be updated carefully in Japan.

Two hundred and ten pneumococcal isolates underwent ceftizoxime disk (30 micrograms) screening to predict cephalosporin resistance. Forty-six isolates failed screening with 36 (78%) demonstrating intermediate/resistant MICs. Sensitivity and specificity were 100 and 95%, respectively. The ceftizoxime disk screen is an effective method of identifying potentially cephalosporin-resistant isolates.

During recent years new mechanisms of beta-lactam resistance have developed with the genetic origin on the chromosome or plasmids. Nevertheless, most multicenter studies can demonstrate that cefotaxime has retained its antibacterial activity toward the relevant species. However, it is important to follow the development of resistance closely in hospitals, where epidemic outbreaks of bacterial strains with extended-spectrum beta-lactamases can create difficulties in the treatment of infectious diseases.