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Background: Disparate and rapidly changing practice recommendations from major professional infectious diseases societies for managing non-severe infections caused by extended-spectrum β-lactamase-producing Enterobacterales might hamper carbapenem stewardship. We aimed to understand the real-world management of extended-spectrum cephalosporin-resistant (ECR) Enterobacterales infections in US hospitals and factors influencing preference for carbapenems over alternative treatments., Methods: This retrospective cohort study included adults (aged ≥18 years) admitted to hospital with ECR Enterobacterales infections in the PINC AI database. Antibiotic regimens were assessed during empirical and targeted treatment periods and by infection severity and site. Likelihood of receiving targeted carbapenems over time and before or after initial release of the Infectious Diseases Society of America (IDSA) guidance on Sept 8, 2020, was established with generalised estimating equations controlling for patient, hospital, and temporal confounders., Findings: Between Jan 1, 2018, and Dec 31, 2021, 30 041 inpatient encounters with ECR Enterobacterales infections were identified at 168 US hospitals, of which 16 006 (53·3%) encounters were in women and 14 035 (46·7%) were in men, with a mean age of 67·3 years (SD 15·1). Although few patients received carbapenems empirically (5324 [17·7%] of 30 041), many did so as targeted treatment (17 518 [58·3%] of 30 041), including subgroups of patients without septic shock (3031 [45·6%] of 6651) and patients with urinary tract infections without septic shock (1845 [46·8%] of 3943) in whom specific narrower-spectrum alternatives were active. Transitions from non-carbapenem to carbapenem antibiotics occurred most often on the day that the ECR phenotype was reported, regardless of illness severity. Carbapenems were the predominant choice to treat ECR Enterobacterales infections over time (adjusted odds ratio 1·00 [95% CI 1·00-1·00]), with no additional immediate change (1·07 [0·95-1·20]) or sustained change (0·99 [0·98-1·00]) after IDSA guidance release., Interpretation: High carbapenem use in targeting non-severe ECR Enterobacterales infections in US hospitals predates 2020 IDSA guidance and has persisted thereafter. Efforts to increase awareness and implementation of recommendations among clinicians to use carbapenem-sparing alternatives in ECR Enterobacterales infections might decrease global carbapenem selective pressure., Funding: US National Institutes of Health Intramural Research Program, National Institute of Allergy and Infectious Diseases, and US Food and Drug Administration., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The emergence and spread of Neisseria gonorrhoeae with resistance to oral antibiotics have led to difficulty in treating gonorrhea. We review drug resistance in N. gonorrhoeae with a particular emphasis on resistance to fluoroquinolones, cefixime and azithromycin. Materials and Methods: Literature selected from peer reviewed journals listed in MEDLINE®/PubMed® from 1943 to 2009 and from resources cited in those articles was reviewed comprehensively. Results: Due to the spread of fluoroquinolone resistant N. gonorrhoeae fluoroquinolones are no longer recommended for the treatment of gonorrhea. The emergence of N. gonorrhoeae with a mosaic penicillin-binding protein 2 associated with oral cephalosporin resistance has threatened cefixime treatment for gonorrhea. Emergence of N. gonorrhoeae with high level resistance to azithromycin has also been documented. However, injectable antibiotics (sepctinomycin and ceftriaxone) retain their activity against N. gonorrhoeae. To monitor drug resistance in N. gonorrhoeae several national and international programs have become functional. Conclusions: Oral regimens for the treatment of gonorrhea are limited. At present to our knowledge ceftriaxone is the most reliable and available agent for the treatment of gonorrhea. To prevent the further emergence and international spread of drug resistance, and allow for the selection of appropriate treatments, a comprehensive global program is needed including surveillance for drug resistance in N. gonorrhoeae and collection of patient epidemiological data. Clinicians should effectively treat patients with gonorrhea, always being conscious of local trends of drug resistance in N. gonorrhoeae, and should perform culture and antimicrobial susceptibility testing in those with persistent gonorrhea after treatment. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are needed to inform public health action., Methods: Using data from patients hospitalized in a cohort of 890 U.S. hospitals during the period 2012-2017, we generated national case counts for both hospital-onset and community-onset infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase (ESBL) production, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant acinetobacter species, and MDR Pseudomonas aeruginosa ., Results: The hospital cohort in the study accounted for 41.6 million hospitalizations (>20% of U.S. hospitalizations annually). The overall rate of clinical cultures was 292 cultures per 1000 patient-days and was stable throughout the time period. In 2017, these pathogens caused an estimated 622,390 infections (95% confidence interval [CI], 579,125 to 665,655) among hospitalized patients. Of these infections, 517,818 (83%) had their onset in the community, and 104,572 (17%) had their onset in the hospital. MRSA and ESBL infections accounted for the majority of the infections (52% and 32%, respectively). Between 2012 and 2017, the incidence decreased for MRSA infection (from 114.18 to 93.68 cases per 10,000 hospitalizations), VRE infection (from 24.15 to 15.76 per 10,000), carbapenem-resistant acinetobacter species infection (from 3.33 to 2.47 per 10,000), and MDR P. aeruginosa infection (from 13.10 to 9.43 per 10,000), with decreases ranging from -20.5% to -39.2%. The incidence of carbapenem-resistant Enterobacteriaceae infection did not change significantly (from 3.36 to 3.79 cases per 10,000 hospitalizations). The incidence of ESBL infection increased by 53.3% (from 37.55 to 57.12 cases per 10,000 hospitalizations), a change driven by an increase in community-onset cases., Conclusions: Health care-associated antimicrobial resistance places a substantial burden on patients in the United States. Further work is needed to identify improved interventions for both the inpatient and outpatient settings. (Funded by the Centers for Disease Control and Prevention.)., (Copyright © 2020 Massachusetts Medical Society.)

In this cohort of Escherichia coli and Klebsiella spp hospital-onset bacteremia, isolated fluoroquinolone resistance had a larger relative impact on mortality than other phenotypic resistance patterns. This finding may support stewardship efforts targeting unnecessary fluoroquinolone use and increased attention from infection prevention and control departments.

This study examines in vitro antimicrobial resistance data from Escherichia coli isolates obtained from urine samples of U.S. outpatients between 2000 and 2010 using The Surveillance Network (TSN). Antimicrobial susceptibility results (n = 12,253,679) showed the greatest increases in E. coli resistance from 2000 to 2010 for ciprofloxacin (3% to 17.1%) and trimethoprim-sulfamethoxazole (TMP-SMX) (17.9% to 24.2%), whereas nitrofurantoin (0.8% to 1.6%) and ceftriaxone (0.2% to 2.3%) showed minimal change. From 2000 to 2010, the antimicrobial resistance of urinary E. coli isolates to ciprofloxacin and TMP-SMX among outpatients increased substantially.

We investigated the clinical and microbiologic features of 300 cases of cephalosporin-resistant Escherichia coli producing extended-spectrum β-lactamase (ESBL) or plasmid-mediated AmpC β-lactamase (pAmpC) at three medical centers in the United States. Solid-organ malignancy, connective tissue disease, and a recent history of surgery were more common among pAmpC-producing cases (n = 49), whereas urinary catheter at enrollment, diabetes, and hospitalization in the past year were more common among ESBL-producing cases (n = 233). The factors independently associated with clinical outcome were the following: the presence of cardiovascular disease (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.29 to 6.43), intra-abdominal infection (OR, 6.35; 95% CI, 1.51 to 26.7), other or multiples sources of infection (OR, 8.12; 95% CI, 2.3 to 28.6), age of 65 years or greater (OR, 0.43; 95% CI, 0.2 to 0.95), favorable baseline health status (OR, 0.39; 95% CI, 0.16 to 0.95), and appropriate empirical antimicrobial therapy given in the first 72 h (OR, 0.42; 95% CI, 0.20 to 0.88). β-Lactamase genes responsible for cephalosporin resistance were identified in 291 cases. CTX-M-type ESBLs accounted for 72.0%. Of those, 88.0% were CTX-M-15. The next most common type was CMY-type pAmpC (16.7%), followed by SHV- and TEM-type ESBLs (6.3 and 1.3%, respectively). Seven cases (2.3%) had KPC-type β-lactamase. Ertapenem, imipenem, meropenem, doripenem, piperacillin-tazobactam, amikacin, nitrofurantoin, and tigecycline were highly active, with greater than 90% of the isolates being susceptible. Cefepime was less active, with only 74.2% being susceptible due to the predominance of CTX-M-15. These findings have implications in the selection of appropriate empirical therapy when infection due to cephalosporin-resistant E. coli is suspected.

CTX-M-type beta-lactamases are increasing among US Enterobacteriaceae isolates. Of 2,165 non-Typhi Salmonella isolates submitted in 2007 to the National Antimicrobial Resistance Monitoring System, 100 (4.6%) displayed elevated MICs (≥2 mg/L) of ceftriaxone or ceftiofur. Three isolates (serotypes Typhimurium, Concord, and I 4,5,12:i:-) contained bla(CTX-M-5), bla(CTX-M-15), and bla(CTX-M-55/57), respectively.

Objective: We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella (NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a β-lactamase., Methods: In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥ 2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of β-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (bla(TEM), bla(OXA), bla(SHV), bla(CTX-M), bla(PSE), and bla(CMY)). Plasmid location of bla(CMY) was confirmed by transforming plasmids into Escherichia coli., Results: Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more β-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC β-lactamase gene bla(CMY.) Other β-lactamase genes detected included 11 bla(TEM-1), 3 bla(PSE-1), 2 bla(OXA-1), and 1 bla(CTX-M-15). The ceftriaxone MIC values for the bla(CMY)-containing isolates ranged from 4 to 64 mg/L; all bla(CMY)-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines., Conclusions: Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase β-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all bla(CMY)-containing isolates were classified as resistant to ceftriaxone (MIC ≥ 4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae.

Third-generation cephalosporin resistance of Salmonella and commensal Escherichia coli isolates from cattle in the United States is predominantly conferred by the cephamycinase CMY-2, which inactivates beta-lactam antimicrobial drugs used to treat a wide variety of infections, including pediatric salmonellosis. The emergence and dissemination of bla(CMY-2)(-)-bearing plasmids followed and may in part be the result of selection pressure imposed by the widespread utilization of ceftiofur, a third-generation veterinary cephalosporin. This study assessed the potential effects of ceftiofur on bla(CMY-2) transfer and dissemination by (i) an in vivo experimental study in which calves were inoculated with competent bla(CMY-2)-bearing plasmid donors and susceptible recipients and then subjected to ceftiofur selection and (ii) an observational study to determine whether ceftiofur use in dairy herds is associated with the occurrence and frequency of cephalosporin resistance in Salmonella and commensal E. coli. The first study revealed bla(CMY-2) plasmid transfer in both ceftiofur-treated and untreated calves but detected no enhancement of plasmid transfer associated with ceftiofur treatment. The second study detected no association (P = 0.22) between ceftiofur use and either the occurrence of ceftiofur-resistant salmonellosis or the frequency of cephalosporin resistance in commensal E. coli. However, herds with a history of salmonellosis (including both ceftiofur-resistant and ceftiofur-susceptible Salmonella isolates) used more ceftiofur than herds with no history of salmonellosis (P = 0.03) These findings fail to support a major role for ceftiofur use in the maintenance and dissemination of bla(CMY-2)-bearing plasmid mediated cephalosporin resistance in commensal E. coli and in pathogenic Salmonella in these dairy cattle populations.

It has long been acknowledged that the cephalosporin breakpoints used in most European countries and the USA fail to detect many or most extended spectrum beta-lactamases (ESBLs) in Enterobacteriaceae and that all ESBLs are clinically significant. Therefore, microbiological laboratories have undertaken not only regular cephalosporin susceptibility tests based on breakpoints, but also special tests to detect all ESBLs. An increasing accumulation of clinical data implies that the clinical success of third generation cephalosporin therapy is related more to the minimum inhibitory concentration (MIC) than to the presence or absence of an ESBL. However, the breakpoints must be lower than those previously recommended by many breakpoint committees. In Europe, this adjustment has been achieved by EUCAST (European Committee on Antimicrobial Susceptibility Testing) through the ongoing process of harmonising European breakpoints. In the USA, the CLSI recently voted to adopt similar guidelines but are waiting to implement these while revising other beta-lactam breakpoints. As Enterobacteriaceae are becoming increasingly resistant, a less 'diehard' interpretation of the relationship among MICs, ESBLs and clinical outcome may provide therapeutic alternatives in difficult situations.

The National Antimicrobial Resistance Monitoring System monitors susceptibility among Enterobacteriaceae in humans in the United States. We studied isolates exhibiting decreased susceptibility to quinolones (nalidixic acid MIC >32 microg/mL or ciprofloxacin MIC > or =0.12 microg/mL) and extended-spectrum cephalosporins (ceftiofur or ceftriaxone MIC > or =2 microg/mL) during 1996-2004. Of non-Typhi Salmonella, 0.19% (27/14,043) met these criteria: 11 Senftenberg; 6 Typhimurium; 3 Newport; 2 Enteridis; and 1 each Agona, Haifa, Mbandaka, Saintpaul, and Uganda. Twenty-six isolates had gyrA mutations (11 at codon 83 only, 3 at codon 87 only, 12 at both). All Senftenberg isolates had parC mutations (S801 and T57S); 6 others had the T57S mutation. The Mbandaka isolate contained qnrB2. Eight isolates contained bla(CMY-2); 1 Senftenberg contained bla(CMY-23). One Senftenberg and 1 Typhimurium isolate contained bla(SHV-12); the Mbandaka isolate contained bla(SHV-30). Nine Senftenberg isolates contained bla(OXA-1) contained bla(OXA-9). Further studies should address patient outcomes, risk factors, and resistance dissemination prevention strategies.

Third-generation cephalosporin (3GC) antimicrobials are the drugs of choice for treatment of salmonellosis in children. Salmonella isolated in the USA are assayed by the National Antimicrobial Resistance Monitoring System (NARMS) for resistance to antimicrobials including first-, second- and third-generation cephalosporins. From 1999 to 2003, 34,411 Salmonella were isolated from animals in the USA, of which 10.9% were found to be resistant to ceftiofur, a 3GC used in animals, whilst only 0.3% were resistant to ceftriaxone, a 3GC used in human medicine. Ceftiofur resistance rose from 4.0% in 1999 to 18.8% in 2003. Isolates from diagnostic laboratories had higher levels of resistance (18.5%), whereas levels in isolates from on-farm (3.4%) and slaughter (7.1%) sources were lower. Animals with a higher than average proportion of resistant Salmonella included cattle (17.6%), horses (19.2%) and dogs (20.8%). Levels in turkeys (6.8%), chickens (7.1%), eggs (3.6%) and swine (4.6%) were lower. Resistance varied between Salmonella serotypes. A few serotypes had significantly high levels, e.g. S. Newport was 70.4% ceftiofur resistant. Resistance was predominantly associated with bla(CMY-2)-encoding plasmids. These data suggest that the acquisition of resistance plasmids and the spread of specific serotypes harbouring these plasmids are driving the observed resistance to ceftiofur in Salmonella animal isolates.

Objective: To test the susceptibility of Streptococcus pneumoniae sinus isolates collected across the United States against commonly used antimicrobial agents., Study Design and Setting: S. pneumoniae sinus isolates (N = 847) collected as part of the Tracking Resistance in the US Today Surveillance Program from 2001 to 2005 were tested against 8 antimicrobial agents., Results: In ascending order, the relative activities (% susceptible) were penicillin (51.8%), trimethoprim/sulfamethoxazole (TMP/SMX) (57.6%), erythromycin (59.5%), cefuroxime (62.0%), amoxicillin/clavulanate (85.5%), clindamycin (86.1%), levofloxacin (99.4%), and linezolid (100%; for 2004 and 2005 respiratory seasons, only). Resistance rates over the 5 years remained generally stable, although resistance to amoxicillin/clavulanate nearly doubled (from 6.5% to 12.9%). Forty percent of isolates were resistant to >or=2 agents tested., Conclusions and Significance: Susceptibility trends among sinus S. pneumoniae isolates appear to have stabilized over the past 5 years. Resistance rates remain elevated for penicillin and macrolides, whereas the high prevalence of multidrug resistance remains a concern.

Objectives: Determining the frequency of antimicrobial resistance amongst bacterial isolates obtained from patients in Intensive Care Units (ICU)., Methods: Study data relating to 2001 to 2003 regarding microbiological isolates was obtained from a laboratory network for the ICUs of 14 third-level hospitals in Bogotá belonging to the Bogotá Bacterial Resistance Control Group (BBRCG). 27,301 isolates were obtained and their susceptibility profiles were analysed using WHONET 5.3., Results: Staphylococcus aureus, Escherichia coli, coagulase negative Staphylococci (CNS), Pseudomonas aeruginosa y Klebsiella pneumoniae were the most commonly found microorganisms. Oxacillin-resistance rate ranged from 61% at 63% during 2001 to 2003 amongst S. aureus isolates and 78% to 83% amongst coagulase negative Staphylococci (CNS). E. coli resistance to third generation cephalosporines was found to be about 10% and over 20% to ciprofloxacin. K. pneumoniae isolates' resistance to third-generation cephalosporines was found to be more than 30% in 2001. P. aeruginosa resistance to all but a few antibiotics was found to be over 30% and multirresistance frequency was found to be 16% to 24%., Conclusion: The antimicrobial resistance rates found in the ICU of hospitals in Bogotá were higher than those reported in surveillance studies in the USA, Europe or other Latin-American cities.

There has been recent concern raised over the detection, prevalence, and clinical implications of infection with Escherichia coli and Klebsiella spp. which produce extended-spectrum beta-lactamases (ESBLs). These enzymes hydrolyze beta-lactams including the cephalosporins (i.e., ceftazidime, ceftriaxone, cefotaxime), thus frequently leading to treatment failures. Standard in vitro testing may report these isolates as susceptible when in fact they are resistant in vivo. As a result of this phenomenon, additional testing for suspected isolates is recommended nationally. We surveyed 28 Connecticut hospitals from 1998-2002 to determine if these institutions utilized screening and confirmation methods for suspected isolates. The number of hospitals which have implemented ESBL detection systems doubled from 11 to 22 over the study period. Currently, 15 of the 22 laboratories conduct both screening and confirmatory testing. This expanded testing will be of great assistance to clinicians in optimizing the clinical care of patients with Gramnegative infections.

Background: This study evaluated the clinical and economic impact of the emergence of third-generation cephalosporin-resistant Enterobacter species., Methods: Mortality, length of hospitalization, and hospital charges were examined in a cohort that was selected from a group of 477 patients with initial cultures that yielded a third-generation cephalosporin-susceptible Enterobacter species. Case patients (n = 46) had subsequent cultures yielding a third-generation cephalosporin-resistant Enterobacter species. Control patients (n = 113) who did not develop resistance were matched to cases on site of Enterobacter infection and length of hospitalization prior to isolation of the initial susceptible organism. Multivariable analyses were used to adjust for confounding., Results: Twenty-six percent of cases died vs 13% of controls (P =.06). The median total hospital stay for cases was 29.5 days (interquartile range [IQR], 20-60) and 19 days for controls (IQR, 13-27; P<.001). The median hospital charge for cases was $79 323 (IQR, $34 546-$161 384) and for controls was $40 406 (IQR, $18 470-$79 005; P<.001). After adjusting for comorbidities, severity of illness, intensive care unit admission, surgery, transfer from another hospital, sex, and age, emergence of resistance was associated with increased mortality (relative risk, 5.02; P =.01), hospital stay (1.5-fold, P<.001), and hospital charges (1.5-fold, P<.001). Emergence of resistance had a median attributable hospital stay of 9 days and an average attributable hospital charge of $29 379., Conclusions: Emergence of antibiotic resistance in Enterobacter species results in increased mortality, hospital stay, and hospital charges. Minimizing resistance in Enterobacter species should be a priority.

Given the propensity for Enterobacteriaceae and clinically significant nonfermentative gram-negative bacilli to acquire antimicrobial resistance, consistent surveillance of the activities of agents commonly prescribed to treat infections arising from these organisms is imperative. This study determined the activities of two fluoroquinolones, levofloxacin and ciprofloxacin, and seven comparative agents against recent clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia using two surveillance strategies: 1) centralized in vitro susceptibility testing of isolates collected from 27 hospital laboratories across the United States and 2) analysis of data from The Surveillance Network Database-USA, an electronic surveillance network comprising more than 200 laboratories nationwide. Regardless of the surveillance method, Enterobacteriaceae, P. aeruginosa, and A. baumannii demonstrated similar rates of susceptibility to levofloxacin and ciprofloxacin. Susceptibilities to the fluoroquinolones approached or exceeded 90% for all Enterobacteriaceae except Providencia spp. (

Objective: To determine the impact of antibiotic resistance on the frequency, clinical features, and management/outcome of mastoiditis attributable to Streptococcus pneumoniae., Design: Retrospective review of the medical records of children with mastoiditis caused by S pneumoniae from September 1993 through December 1998., Patients: Infants and children with pneumococcal mastoiditis cared for at 8 children's hospitals in the United States., Results: Thirty-four children with pneumococcal mastoiditis were identified. The median age of the children was 12 months (range: 2 months-12.5 years); 28 (82%) were

beta-Lactamase production in Canadian isolates of Haemophilus influenzae has remained relatively constant (25-35%) over the last decade despite increasing cefaclor resistance (MIC >/= 32 mg/L). TEM (294/324, 90.7%) and ROB-1 (30/324, 9.3%) prevalence rates among 324 isolates of H. influenzae obtained from across Canada in 1997-1998 were similar (P > 0.05) to previously published reports. However, 66. 7% (26/39) of cefaclor-resistant isolates were ROB-1-positive (P < 0. 001) and the remaining four ROB-1-positive isolates were cefaclor-intermediate (MIC 16 mg/L). Susceptibilities to loracarbef (P < 0.001) and cefprozil were also reduced in the presence of ROB-1 while the activities of cefuroxime, cefotaxime, cefixime and imipenem were similar in both TEM- and ROB-1-positive solates.

Extended-spectrum beta-lactamases (ESBLs) are enzymes produced in some gram-negative bacilli that mediate resistance to extended-spectrum cephalosporins and aztreonam. They are most common in Klebsiella spp. and Escherichia coli but are present in a variety of Enterobacteriaceae. Resistance mediated by these enzymes can be difficult to detect depending on the antimicrobial agents tested. AmpC beta-lactamases are related to the chromosomal enzymes of Enterobacter and Citrobacter spp. and also mediate resistance to extended-spectrum cephalosporins and aztreonam in addition to cephamycins, such as cefoxitin. Unlike ESBLs, however, AmpC beta-lactamases are not inhibited by clavulanic acid or other similar compounds. To assess the abilities of various antimicrobial susceptibility testing methods to detect ESBLs, we sent three ESBL-producing organisms, one AmpC-producing organism, and a control strain that was susceptible to extended-spectrum cephalosporins to 38 laboratories in Connecticut for testing. Eight (21.0%) of 38 labs failed to detect extended-spectrum cephalosporin or aztreonam resistance in any of the ESBL- or AmpC-producing isolates. Errors were encountered with both automated and disk diffusion methods. Conversely, seven (18.4%) labs categorized at least some of the four resistant isolates as potential ESBL producers and reported the results with the extended-spectrum cephalosporins and aztreonam as resistant as suggested by current National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The percentage of laboratories that failed to detect resistance in the ESBL or AmpC isolates ranged from 23.7 to 31.6% depending on the type of enzyme present in the test organism. This survey suggests that many laboratories have difficulty detecting resistance in ESBL and AmpC-producing organisms and may be unaware of the NCCLS guidelines on modifying susceptibility testing reports for ESBL-producing strains.

Objectives: To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone., Design and Patients: Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children's hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review., Outcome: Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone., Results: Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 microgram/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (>/=8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone., Conclusions: Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. (ABSTRACT TRUNCATED)

A total of 1,527 clinically significant outpatient isolates of Streptococcus pneumoniae were prospectively collected in 30 different U.S. medical centers between November 1994 and April 1995. Overall, 23.6% of strains were not susceptible to penicillin, with 14.1% intermediate and 9.5% high-level resistant. The frequencies of recovery of intermediate and high-level resistant strains varied considerably between different medical centers and in different geographic areas. In general, intermediate and high-level penicillin resistance was most common with isolates of S. pneumoniae recovered from pediatric patients. The in vitro activities of 22 other antimicrobial agents were assessed against this collection of isolates. Ampicillin was consistently 1 twofold dilution less active than penicillin. Amoxicillin and amoxicillin-clavulanate were essentially equivalent to penicillin in activity. The rank order of activity for cephalosporins was cefotaxime = ceftriaxone > or = cefpodoxime > or = cefuroxime > cefprozil > or = cefixime > cefaclor = loracarbef > cefadroxil = cephalexin. The National Committee for Clinical Laboratory Standards [Performance Standards for Antimicrobial Susceptibility Testing, Sixth Information Supplement (M100-S6), 1995] has established MIC breakpoints for resistance (i.e., > or = 2 micrograms/ml) with three cephalosporins versus S. pneumoniae, namely, cefotaxime, ceftriaxone, and cefuroxime. The overall percentages of strains resistant to these three antimicrobial agents were 3, 5, and 12, respectively. The overall frequency of resistance was 10% with all three macrolides examined in this study, clarithromycin, erythromycin, and azithromycin. The overall percentages of chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole resistance were 4.3, 7.5, and 18, respectively. The resistance percentages among the cephalosporins, macrolides, chloramphenicol, tetracycline, and trimethoprim-sulfamethoxazole were consistently higher among penicillin-intermediate strains than among susceptible isolates and even higher still among organisms expressing high-level penicillin resistance. Multiply resistant strains represented 9.1% of the organisms examined in this study. Finally, rifampin resistance was uncommon (i.e., 0.5%), and vancomycin resistance was not detected. The quinopristin-dalfopristin combination was consistently active at concentrations of 0.25 to 4 micrograms/ml, but rates of resistance could not be determined in the absence of established interpretive criteria for MIC results.

To examine temporal trends in ceftazidime resistance, susceptibility data reported to the National Nosocomial Infections Surveillance system during 1987-1991 were analyzed among nosocomial Enterobacter species, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Linear increases in resistance were observed for Enterobacter species and K. pneumoniae. One hospital experienced a dramatic rise from 1.0% in 1987-1989 to 40% in 1990-1991 (P < .001) in ceftazidime resistance among K. pneumoniae isolates. No increase was observed during this period for P. aeruginosa. Logistic regression analysis confirmed these trends (or the lack thereof) for Enterobacter species and P. aeruginosa; for K. pneumoniae, ceftazidime resistance was found to be increasing among isolates from teaching hospitals and intensive care units. Ceftazidime resistance is an emerging problem that has the potential for dramatic increases. Selective pressures for the development of ceftazidime resistance need to be identified and addressed.