Development of Daptomycin Susceptibility Breakpoints for Enterococcus faecium and Revision of the Breakpoints for Other Enterococcal Species by the Clinical and Laboratory Standards Institute.

Daptomycin is one of the few treatment options for infections caused by enterococci that are resistant to ampicillin and vancomycin, such as vancomycin-resistant Enterococcus faecium. The emergence and clinical significance of daptomycin-resistant enterococci and evolving microbiologic, pharmacokinetic-pharmacodynamic, and clinical data indicated that the pre-2019 Clinical and Laboratory Standards Institute (CLSI) susceptible-only breakpoint of ≤4 µg/mL for daptomycin and enterococci was no longer appropriate. After analyzing data that are outlined in this article, the CLSI Subcommittee on Antimicrobial Susceptibility Testing established new breakpoints for daptomycin and enterococci. For E. faecium, a susceptible dose-dependent (SDD) breakpoint of ≤4 µg/mL was established based on an increased dosage of 8-12 mg/kg/day (≥8 µg/mL-resistant). CLSI suggests infectious diseases consultation to guide daptomycin use for the SDD category. For Enterococcus faecalis and other enterococcal species, revised breakpoints of ≤2 µg/mL-susceptible, 4 µg/mL-intermediate, and ≥8 µg/mL-resistant were established based on a standard dosage of 6 mg/kg/day.

Evidence for clonal expansion after antibiotic selection pressure: pneumococcal multilocus sequence types before and after mass azithromycin treatments.

BACKGROUND: A clinical trial of mass azithromycin distributions for trachoma created a convenient experiment to test the hypothesis that antibiotic use selects for clonal expansion of preexisting resistant bacterial strains. METHODS: Twelve communities in Ethiopia received mass azithromycin distributions every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored by means of nasopharyngeal swab sampling before mass azithromycin distribution and after 4 mass treatments. Swab specimens were tested for Streptococcus pneumoniae, and isolates underwent multilocus sequence typing. RESULTS: Of 82 pneumococcal isolates identified before treatment, 4 (5%) exhibited azithromycin resistance, representing 3 different sequence types (STs): 177, 6449, and 6494. The proportion of isolates that were classified as one of these 3 STs and were resistant to azithromycin increased after 4 mass azithromycin treatments (14 of 96 isolates [15%]; P = .04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P < .0001). The diversity of STs-as calculated by the unbiased Simpson index-decreased significantly after mass azithromycin treatment (P = .045). CONCLUSIONS: Resistant clones present before mass azithromycin treatments increased in frequency after treatment, consistent with the theory that antibiotic selection pressure results in clonal expansion of existing resistant strains.

Failure of clindamycin to eradicate infection with beta-hemolytic streptococci inducibly resistant to clindamycin in an animal model and in human infections.

Inducible clindamycin resistance in beta-hemolytic streptococci remains an underrecognized phenomenon of unknown clinical significance. We performed an evaluation of inducible clindamycin resistance using an animal model as well as retrospectively reviewing the charts of patients treated with clindamycin monotherapy who were infected with beta-hemolytic streptococci inducibly resistant to clindamycin. The neutropenic mouse thigh model of infection was used to evaluate the in vivo activity of clindamycin against beta-hemolytic streptococci, including isolates susceptible, inducibly resistant, or constitutively resistant to clindamycin. The clinical microbiology laboratory information system and pharmacy databases were cross-referenced to identify patients with infections due to inducibly clindamycin-resistant beta-hemolytic streptococci who were treated with clindamycin monotherapy. Medical records of these patients were reviewed to evaluate microbiologic and clinical outcomes. Inducible clindamycin resistance resulted in impaired killing of beta-hemolytic streptococci in the animal model. Though suppressed initially, compared to those with constitutive resistance (P=0.0429), by 48 h, colony counts of inducibly clindamycin-resistant organisms were similar to those of constitutively resistant isolates (P=0.1142). In addition, we identified 8 patients infected with inducibly clindamycin-resistant beta-hemolytic streptococci who experienced clinical and microbiologic failure when treated with clindamycin monotherapy. These patients either improved initially and subsequently failed or never responded to clindamycin therapy. We have demonstrated in a murine model of infection and from human cases that inducible clindamycin resistance in beta-hemolytic streptococci is clinically significant. Routine testing and reporting by clinical laboratories should be encouraged and alternative antimicrobial agents considered when these organisms are encountered in clinical care.

Community-associated extended-spectrum ß-lactamase-producing Escherichia coli infection in the United States.

Background. The occurrence of community-associated infections due to extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli has been recognized as a major clinical problem in Europe and other regions. Methods. We conducted a prospective observational study to examine the occurrence of community-associated infections due to ESBL-producing E. coli at centers in the United States. Five academic and community hospitals and their affiliated clinics participated in this study in 2009 and 2010. Sites of acquisition of the organisms (community-associated or healthcare-associated), risk factors, and clinical outcome were investigated. Screening for the global epidemic sequence type (ST) 131 and determination of the ESBL types was conducted by polymerase chain reaction and sequencing. Results. Of the 291 patients infected or colonized with ESBL-producing E. coli as outpatients or within 48 hours of hospitalization, 107 (36.8%) had community-associated infection (81.5% of which represented urinary tract infection), while the remainder had healthcare-associated infection. Independent risk factors for healthcare-associated infection over community-associated infection were the presence of cardiovascular disease, chronic renal failure, dementia, solid organ malignancy, and hospitalization within the previous 12 months. Of the community-associated infections, 54.2% were caused by the globally epidemic ST131 strain, and 91.3% of the isolates produced CTX-M-type ESBL. Conclusions. A substantial portion of community-onset, ESBL-producing E. coli infections now occur among patients without discernible healthcare-associated risk factors in the United States. This epidemiologic shift has implications for the empiric management of community-associated infection when involvement of E. coli is suspected.

Rapid emergence of echinocandin resistance in Candida glabrata resulting in clinical and microbiologic failure.

We report a case of Candida glabrata candidemia that developed resistance to micafungin within 8 days of initiation of therapy in a patient without previous echinocandin exposure or other known risk factors for clinical or microbiological failure. Pre- and postresistant isolates were confirmed to be isogenic, and sequencing of hot spots known to confer echinocandin resistance revealed a phenylalanine deletion at codon 659 within FKS2.

Development of doxycycline MIC and disk diffusion interpretive breakpoints and revision of tetracycline breakpoints for Streptococcus pneumoniae.

A study was performed to derive susceptibility testing interpretive breakpoints for doxycycline with Streptococcus pneumoniae and to reassess breakpoints for tetracycline using the requirements defined in Clinical and Laboratory Standards Institute (CLSI) document M23-A3. Tetracycline and doxycycline MICs and disk diffusion zone sizes were determined on 189 isolates selected from the 2009-2010 CDC Active Bacterial Core surveillance strain collection according to the testing methods described in CLSI documents M07-A8 and M02-A10. Tetracycline and doxycycline MICs and zones were compared to each other directly, and the reproducibility of MICs and zone diameters for both drugs was determined. Scattergrams of tetracycline MICs versus corresponding zone diameters and doxycycline MICs versus zones were prepared, and analysis indicated that the present CLSI tetracycline MIC and disk breakpoints did not fit the susceptibility data for doxycycline. Doxycycline was 1 to 3 dilutions more potent than tetracycline, especially in strains harboring the tetM resistance determinant. tetM was detected in ≥ 90% of isolates having tetracycline MICs of ≥ 4 µg/ml and in ≥ 90% with doxycycline MICs of ≥ 1. Limited pharmacokinetic/pharmacodynamic (PK/PD) data coupled with application of the error-rate bounded method of analysis suggested doxycycline-susceptible breakpoints of either ≤ 0.25 µg/ml or ≤ 0.5 µg/ml, with intermediate and resistant breakpoints 1 and 2 dilutions higher, respectively. The disk diffusion zone diameter correlates were susceptible at ≥ 28 mm, intermediate at 25 to 27 mm, and resistant at ≤ 24 mm. Revised lower tetracycline MIC breakpoints were suggested as susceptible at ≤ 1 µg/ml, intermediate at 2 µg/ml, and resistant at ≥ 4 µg/ml. Suggested tetracycline disk diffusion zones were identical to those of doxycycline.

Clinical and microbiologic characteristics of cephalosporin-resistant Escherichia coli at three centers in the United States.

We investigated the clinical and microbiologic features of 300 cases of cephalosporin-resistant Escherichia coli producing extended-spectrum ß-lactamase (ESBL) or plasmid-mediated AmpC ß-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). ß-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 ß-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.

Molecular epidemiological analysis of Escherichia coli sequence type ST131 (O25:H4) and blaCTX-M-15 among extended-spectrum-ß-lactamase-producing E. coli from the United States, 2000 to 2009.

Escherichia coli sequence type ST131 (from phylogenetic group B2), often carrying the extended-spectrum-ß-lactamase (ESBL) gene bla(CTX-M-15), is an emerging globally disseminated pathogen that has received comparatively little attention in the United States. Accordingly, a convenience sample of 351 ESBL-producing E. coli isolates from 15 U.S. centers (collected in 2000 to 2009) underwent PCR-based phylotyping and detection of ST131 and bla(CTX-M-15). A total of 200 isolates, comprising 4 groups of 50 isolates each that were (i) bla(CTX-M-15) negative non-ST131, (ii) bla(CTX-M-15) positive non-ST131, (iii) bla(CTX-M-15) negative ST131, or (iv) bla(CTX-M-15) positive ST131, also underwent virulence genotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Overall, 201 (57%) isolates exhibited bla(CTX-M-15), whereas 165 (47%) were ST131. ST131 accounted for 56% of bla(CTX-M-15)-positive- versus 35% of bla(CTX-M-15)-negative isolates (P < 0.001). Whereas ST131 accounted for 94% of the 175 total group B2 isolates, non-ST131 isolates were phylogenetically distributed by bla(CTX-M-15) status, with groups A (bla(CTX-M-15)-positive isolates) and D (bla(CTX-M-15)-negative isolates) predominating. Both bla(CTX-M-15) and ST131 occurred at all participating centers, were recovered from children and adults, increased significantly in prevalence post-2003, and were associated with molecularly inferred virulence. Compared with non-ST131 isolates, ST131 isolates had higher virulence scores, distinctive virulence profiles, and more-homogeneous PFGE profiles. bla(CTX-M-15) was associated with extensive antimicrobial resistance and ST131 with fluoroquinolone resistance. Thus, E. coli ST131 and bla(CTX-M-15) are emergent, widely distributed, and predominant among ESBL-positive E. coli strains in the United States, among children and adults alike. Enhanced virulence and antimicrobial resistance have likely promoted the epidemiological success of these emerging public health threats.

Effect of pneumococcal conjugate vaccine on pneumococcal meningitis.

BACKGROUND: Invasive pneumococcal disease declined among children and adults after the introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, but its effect on pneumococcal meningitis is unclear. METHODS: We examined trends in pneumococcal meningitis from 1998 through 2005 using active, population-based surveillance data from eight sites in the United States. Isolates were grouped into PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV7-related serotypes (6A, 9A, 9L, 9N, 18A, 18B, 18F, 19B, 19C, 23A, and 23B), and non-PCV7 serotypes (all others). Changes in the incidence of pneumococcal meningitis were assessed against baseline values from 1998-1999. RESULTS: We identified 1379 cases of pneumococcal meningitis. The incidence declined from 1.13 cases to 0.79 case per 100,000 persons between 1998-1999 and 2004-2005 (a 30.1% decline, P<0.001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P<0.001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P<0.001) among patients of all ages. Although rates of PCV7-related-serotype disease decreased by 32.1% (P=0.08), rates of non-PCV7-serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P<0.001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P=0.01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P=0.03). CONCLUSIONS: Rates of pneumococcal meningitis have decreased among children and adults since PCV7 was introduced. Although the overall effect of the vaccine remains substantial, a recent increase in meningitis caused by non-PCV7 serotypes, including strains nonsusceptible to antibiotics, is a concern.

Detection of favorable oral cephalosporin-clavulanate interactions by in vitro disk approximation susceptibility testing of extended-spectrum-Beta-lactamase-producing members of the enterobacteriaceae.

Extended-spectrum-beta-lactamase (ESBL)-producing members of the Enterobacteriaceae are often resistant to multiple drug classes, making therapy of urinary infections with oral antibiotics difficult. Previously it was shown that amoxicillin-clavulanate can provide clavulanate inhibition of ESBLs and protect an oral cephalosporin present in combination when tested by broth microdilution. This study has shown that disk approximation testing could detect favorable cephalosporin-clavulanate interactions among a group of 101 previously characterized members of the Enterobacteriaceae with CTX-M, SHV, or TEM ESBLs.

Dose of trimethoprim-sulfamethoxazole to treat skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus.

We undertook this study to investigate whether treatment with a higher dose of trimethoprim-sulfamethoxazole (TMP/SMX) led to greater clinical resolution in patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). A prospective, observational cohort with nested case-control study was performed at a public tertiary health system. Among patients with MRSA SSTIs during the period from May 2008 to September 2008 who received oral monotherapy with TMP/SMX and whose clinical outcome was known, the clinical characteristics and outcomes were compared between patients treated with a high dose of TMP/SMX (320 mg/1,600 mg twice daily) for 7 to 15 days and patients treated with the standard dose of TMP/SMX (160 mg/800 mg twice daily) for 7 to 15 days. In patients with MRSA SSTIs, those treated with the high dose of TMP/SMX (n = 121) had clinical characteristics similar to those of patients treated with the standard dose of TMP/SMX (n = 170). The only exception was a higher proportion of patients with a history of trauma upon admission among the patients treated with the higher dose. The proportion of patients with clinical resolution of infection was not different in the two groups (88/121 [73%] versus 127/170 [75%]; P = 0.79). The lack of significance remained in patients with abscess upon stratified analysis by whether surgical drainage was performed. The study found that patients with MRSA SSTIs treated with the higher dose of TMP/SMX (320/1,600 mg twice daily) for 7 to 15 days had a similar rate of clinical resolution as patients treated with the standard dose of TMP/SMX (160/800 mg twice daily) for 7 to 15 days.

Evaluation of disk approximation and single-well broth tests for detection of inducible clindamycin resistance in Streptococcus pneumoniae.

This study evaluated an agar disk diffusion D-zone test and an erythromycin-clindamycin (ERY + CLI) single-well broth test for inducible CLI resistance in Streptococcus pneumoniae. The standard CLSI disk approximation test and a single-well combination test incorporating 1 plus 0.5 µg/ml ERY + CLI detected >96% of isolates containing the ermB determinant.

Collaborative evaluation of an erythromycin-clindamycin combination well for detection of inducible clindamycin resistance in beta-hemolytic streptococci by use of the CLSI broth microdilution method.

Constitutive or inducible clindamycin resistance can occur in beta-hemolytic streptococci due to the presence of an erm gene. The Clinical and Laboratory Standards Institute (CLSI) has recommended a disk approximation test (D-zone test) with erythromycin and clindamycin disks and a single-well broth test combining erythromycin and clindamycin for detection of inducible clindamycin resistance in staphylococci, but only a disk approximation test for the beta-hemolytic streptococci. This collaborative study assessed two different erythromycin and clindamycin concentration combinations in single wells (1 µg/ml + 0.25 µg/ml [erythromycin plus clindamycin] and 1 µg/ml + 0.5 µg/ml) with three different brands of Mueller-Hinton broth supplemented with 3% lysed horse blood for testing of frozen panels prepared for this study. All labs performed the D-zone test as described by the CLSI. A total of 155 nonduplicate streptococcal isolates (50 group A, 48 group B, 28 group C, and 29 group G isolates) were tested; 99 isolates showed inducible resistance by the D-zone test. There were some differences noted based upon the test medium. The sensitivity of the erythromycin plus clindamycin combination of 1 µg/ml + 0.25 µg/ml was 91 to 100%, while the sensitivity of the combination of 1 µg/ml + 0.5 µg/ml was 95 to 100%. Specificity overall was 98%. The slightly higher sensitivity of the combination of 1 µg/ml + 0.5 µg/ml is recommended. This study has demonstrated that a single-well microdilution test incorporating erythromycin and clindamycin in combination is a sensitive and specific indicator of inducible clindamycin resistance and could be included in routine test panels.

Increased penicillin nonsusceptibility of nonvaccine-serotype invasive pneumococci other than serotypes 19A and 6A in post-7-valent conjugate vaccine era.

According to population-based invasive pneumococcal surveillance in the United States during 2007, 898 (26%) of 3,511 isolates were penicillin nonsusceptible. Non-7-valent pneumococcal conjugate vaccine (PCV7) serotypes other than 19A accounted for 40% of these penicillin-nonsusceptible isolates; of these, serotypes 15A (11%), 23A (8%), 35B (8%), and 6C (5%) were most common (cumulatively 32% of penicillin-nonsusceptible isolates). Each except 6C represented a single serotype and clonal complex combination that predated the introduction of PCV7. We evaluated the genetic characteristics and nonsusceptibility to penicillin of non- PCV7 serotypes, and we found increased proportions of specific penicillin-nonsusceptible clones in serotypes 15A, 23A, 35B, and 6C, which potentially indicates a basic change of population structure within these individual serotypes.

Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial.

BACKGROUND: It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities. METHODS AND FINDINGS: In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1-10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%-8.9%) at baseline, to 46.9% (37.5%-57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%-13.3%) at month 12, significantly lower than the treated group (p < 0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%-4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year. CONCLUSIONS: This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00322972. Please see later in the article for the Editors' Summary.

Detection of SHV-type extended-spectrum beta-lactamase in Enterobacter isolates.

One hundred four Enterobacter isolates were tested by standard CLSI disk diffusion methods for detecting extended-spectrum beta-lactamases (ESBLs) and with cefepime-clavulanate disk combinations. SHV-12 was produced by 8.7% of isolates. The cefepime-clavulanate combination provided 88% sensitivity and 91% specificity for the detection of SHV-12 ESBL.

Detection of CTX-M-type extended-spectrum beta-lactamase (ESBLs) by testing with MicroScan overnight and ESBL confirmation panels.

CTX-M extended-spectrum beta-lactamases (ESBLs) have emerged as the most common type of ESBL globally, their incidence easily surpassing those of SHV and TEM ESBLs in most locales. This study compared the performance of two MicroScan dried panels with CLSI reference broth microdilution and disk diffusion methods on a collection of genetically characterized ESBL-producing isolates. These included 64 Enterobacteriaceae isolates that produced CTX-M8, -14, -15, or -16 according to PCR and sequencing of the bla gene, 17 isolates that produced a SHV or TEM ESBL, and 19 that produced both CTX-M and SHV ESBLs. Each isolate was tested by a frozen reference microdilution panel, the MicroScan ESbetaL plus confirmation panel, and a routine dried panel containing streamlined ESBL confirmation dilutions (MicroScan Neg MIC panel type 32) that included cefotaxime and ceftazidime tested alone or with a fixed concentration of 4 microg/ml of clavulanate. Each isolate was also tested by the standard CLSI double-disk confirmation tests. The disk diffusion method detected all ESBL-producing isolates, the frozen reference panel detected 90% of isolates (10 out of 100 could not be analyzed because of off-scale MICs that exceeded the clavulanate combination concentrations in the panel), the ESbetaL plus panel detected 98% (1 missed and 1 off scale), and the streamlined ESBL panel detected 95% (5 off scale). Very high MICs for a few strains that produced SHV or both CTX-M and SHV ESBLs precluded noting the required three twofold-dilution differences with clavulanate needed to confirm an ESBL primarily in the reference panel and the Neg type 32 panel.

Detection of inducible clindamycin resistance in beta-hemolytic streptococci by using the CLSI broth microdilution test and erythromycin-clindamycin combinations.

This study assessed an erythromycin-clindamycin (ERY-CC) broth test for inducible CC resistance in beta-hemolytic streptococci. One hundred one isolates of groups A, B, C, F, and G were tested by the CLSI broth microdilution method. Combinations of 1 and 0.25 microg/ml or 0.5 and 0.25 microg/ml of ERY and CC, respectively, detected all inducible isolates.

Antimicrobial susceptibility testing: a review of general principles and contemporary practices.

An important task of the clinical microbiology laboratory is the performance of antimicrobial susceptibility testing of significant bacterial isolates. The goals of testing are to detect possible drug resistance in common pathogens and to assure susceptibility to drugs of choice for particular infections. The most widely used testing methods include broth microdilution or rapid automated instrument methods that use commercially marketed materials and devices. Manual methods that provide flexibility and possible cost savings include the disk diffusion and gradient diffusion methods. Each method has strengths and weaknesses, including organisms that may be accurately tested by the method. Some methods provide quantitative results (eg, minimum inhibitory concentration), and all provide qualitative assessments using the categories susceptible, intermediate, or resistant. In general, current testing methods provide accurate detection of common antimicrobial resistance mechanisms. However, newer or emerging mechanisms of resistance require constant vigilance regarding the ability of each test method to accurately detect resistance.

Oral and parenteral therapeutic options for outpatient urinary infections caused by enterobacteriaceae producing CTX-M extended-spectrum beta-lactamases.

Effective therapeutic options are needed for community-onset urinary tract infections due to Escherichia coli strains that produce CTX-M extended-spectrum beta-lactamases. We examined 46 urinary isolates producing CTX-M against several oral or long-acting parenteral antimicrobial agents. Approximately 90% were susceptible to fosfomycin and to a combination of cefdinir plus amoxicillin-clavulanate. All were susceptible to ertapenem.