Prevalence of blaCTX-M Genes in Gram-Negative Bloodstream Isolates across 66 Hospitals in the United States.

Understanding bacterial species at greatest risk for harboring blaCTX-M genes is necessary to guide antibiotic treatment. We identified the species-specific prevalence of blaCTX-M genes in Gram-negative clinical isolates from the United States. Twenty-four microbiology laboratories representing 66 hospitals using the GenMark Dx ePlex blood culture identification Gram-negative (BCID-GN) panel extracted blood culture results from April 2019 to July 2020. The BCID-GN panel includes 21 Gram-negative targets. Along with identifying blaCTX-M genes, it detects major carbapenemase gene families. A total of 4,209 Gram-negative blood cultures were included. blaCTX-M genes were identified in 462 (11%) specimens. The species-specific prevalence of blaCTX-M genes was as follows: Escherichia coli (16%), Klebsiella pneumoniae (14%), Klebsiella oxytoca (6%), Salmonella spp. (6%), Acinetobacter baumannii (5%), Enterobacter species (3%), Proteus mirabilis (2%), Serratia marcescens (0.6%), and Pseudomonas aeruginosa (0.5%). blaCTX-M prevalence was 26%, 24%, and 22% among participating hospitals in the District of Columbia, New York, and Florida, respectively. Carbapenemase genes were identified in 61 (2%) organisms with the following distribution: blaKPC (59%), blaVIM (16%), blaOXA (10%), blaNDM (8%), and blaIMP (7%). The species-specific prevalence of carbapenemase genes was as follows: A. baumannii (5%), K. pneumoniae (3%), P. mirabilis (3%), Enterobacter species (3%), Citrobacter spp. (3%), P. aeruginosa (2%), E. coli (<1%), K. oxytoca (<1%), and S. marcescens (<1%). Approximately 11% of Gram-negative organisms in our US cohort contain blaCTX-M genes. blaCTX-M genes remain uncommon in organisms beyond E. coli, K. pneumoniae, and K. oxytoca Future molecular diagnostic panels would benefit from the inclusion of plasmid-mediated ampC and SHV and TEM extended-spectrum beta-lactamase (ESBL) targets.

Evaluation of rapid polymerase chain reaction-based organism identification of gram-positive cocci for patients with a single positive blood culture.

For patients with a single-positive blood culture growing gram-positive cocci, organism identification can provide supportive information for differentiating contamination from infection. We investigated the effect of a rapid blood culture identification panel (BCID) on vancomycin-prescribing patterns and patient outcomes for single positive blood culture (PBC) growing gram-positive cocci. Adult patients with single-positive blood culture growing gram-positive cocci with conventional organism identification (pre-BCID) were compared with organism identification by BCID (post-BCID). Antimicrobial Stewardship Program (ASP) review of PBC was performed in both study groups. Vancomycin prescribing patterns were studied. Secondary endpoints were the incidence of nephrotoxicity, length of stay (LOS), readmission rate, mortality, and hospital costs. A total of 188 patients (86 pre-BCID, 102 post-BCID) were included. Organism identification was known 21 h sooner in the post-BCID group (P < 0.001). Coagulase-negative staphylococci were the most commonly isolated organisms (73%). In patients where vancomycin was deemed unnecessary (n = 133), vancomycin use (51% pre-BCID vs 36% post-BCID; P = 0.09) and time from culture positivity to vancomycin discontinuation (1.5 vs. 1.7 days; P = 0.92) did not differ between groups. We found no differences in the development of nephrotoxicity, LOS, readmission, mortality, or hospital costs. Earlier identification of single positive blood culture growing gram-positive cocci did not significantly influence prescribing patterns of vancomycin. However, baseline antimicrobial stewardship review of single positive blood culture growing gram-positive cocci may have lessened the opportunity for detectable differences. Larger studies, accounting for the impact of ASP intervention, should be performed to determine the value of each individual component.

A case-control study evaluating the unnecessary use of intravenous broad-spectrum antibiotics in presumed sepsis and septic-shock patients in the emergency department.

Objectives: Recognition of sepsis frequently occurs in emergency departments. To evaluate the appropriateness of empiric antibiotic use in the setting of suspected sepsis in emergency department, the percentages of bacterial infection and antibiotic-related adverse drug effects were quantified in an emergency department at an academic medical center. Methods: We retrospectively reviewed electronic medical records of adults who presented to the emergency department between January 2018 and June 2018 with suspected sepsis (defined as having ≥2 systemic inflammatory response syndrome [SIRS] criteria) and received ≥1 dose of intravenous broad-spectrum antibiotic. Results: In total, 218 patients were included in the final analysis. Moreover, 19.3% of these patients had confirmed bacterial infections; 44.5% had suspected bacterial infections; and 35.9% did not have bacterial infection. Elevated SIRS score (ie, ≥2) and Quick Sequential Organ Failure Assessment (qSOFA) score (ie, ≥2) were not associated with the presence of bacterial infections. We identified 90-day Clostridioides difficile infections in 7 patients and drug-resistant organism infections in 6 patients, regardless of the presence of bacterial infections. Conclusions: A high number of patients received intravenous broad-spectrum antibiotics in the emergency department without confirmed or suspected bacterial infections that were supported by microbiologic cultures, radiographic imaging, or other symptoms of infections. Most patients who were initially admitted to the emergency department with suspected sepsis were discharged home after receiving 1 dose of intravenous antibiotic. Patients who were initially screened using SIRS score and who received broad-spectrum antibiotics in the emergency department were without confirmed or suspected bacterial infection.

In vitro activity of ceftolozane-tazobactam and ceftazidime-avibactam against Pseudomonas aeruginosa isolated from patients with cystic fibrosis.

Pseudomonas aeruginosa is a commonly isolated pathogen in adults with cystic fibrosis (CF). Antimicrobial resistance is an escalating problem due to chronic colonization and frequent antimicrobial exposure. Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) exhibit promising activity against antimicrobial resistant organisms, including P. aeruginosa. A retrospective review was conducted comparing the in vitro activities of C/T and CZA against 42 P. aeruginosa isolates from the respiratory tract of 32 adults with CF. The first isolate per patient per year that underwent susceptibility testing for C/T, CZA, and colistin was included. C/T was more susceptible than CZA (60% versus 43%). Thirty-eight (90%) isolates were considered highly drug resistant and demonstrated higher C/T susceptibilities compared to CZA (55% versus 45%). These results suggest using C/T while awaiting susceptibilities when standard antipseudomonal agents cannot be used.

Clinical experience with ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than Klebsiella pneumoniae.

BACKGROUND: Ceftazidime/avibactam is a newly approved ß-lactam/ß-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited. METHODS: A retrospective case series was performed to evaluate patients treated with ceftazidime/avibactam for infections caused by organisms other than K. pneumoniae at our institution over a 1-year period. Patients aged at least 18 years who received at least one dose of ceftazidime/avibactam were eligible for inclusion. Clinical and microbiological data were collected, and investigators assessed adverse effects, microbiological cure, clinical success, and 30-day in-hospital mortality following completion of ceftazidime/avibactam therapy. RESULTS: Ten patients were included. The most common index infection was pneumonia (n = 6/13, 46%) and the most frequently isolated organism was Pseudomonas aeruginosa (n = 8/21, 38%). Fifty percent of patients received ceftazidime/avibactam as monotherapy. Microbiological cure was achieved in 67% (n = 6/9) of patients and 70% (n = 7/10) of patients met criteria for clinical success. The 30-day in-hospital mortality rate was 30%. No patients experienced adverse events because of ceftazidime/avibactam therapy. CONCLUSIONS: For infections caused by antibiotic-resistant Gram-negative organisms other than K. pneumoniae, clinical and microbiological success rates for patients treated with ceftazidime/avibactam were similar to those that have been reported for K. pneumoniae. Ceftazidime/avibactam appears to be a promising treatment option for infections caused by a variety of resistant Gram-negative organisms when limited alternatives exist.

Prolonged linezolid use is associated with the development of linezolid-resistant Enterococcus faecium.

We assessed risk factors for and outcomes of linezolid-resistant vancomycin-resistant Enterococcus faecium (LRVREF) bacteremia over 7 years. Thirty-four LRVREF cases were matched to 68 linezolid-susceptible VREF controls. The odds of bacteremia with LRVREF increased by 7% for each additional day of prior linezolid exposure.

Probiotics and Fecal Microbiota Transplant for Primary and Secondary Prevention of Clostridium difficile Infection.

Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea and is associated with an increased risk of mortality. The use of probiotics and fecal microbiota transplantation (FMT) has been studied to reduce the incidence and severity of this infection, but variable efficacy and safety data have been reported. Probiotics are hypothesized to be effective in the management of CDI through a number of mechanisms that include maintenance of normal gastrointestinal flora, antimicrobial and antitoxin properties, and immunomodulatory effects. Despite promising results in small trials and meta-analyses, prospective, randomized, controlled trials have not demonstrated probiotics to be effective in the primary prevention of C. difficile-associated diarrhea (CDAD). Probiotics may be effective for secondary prevention in patients with recurrent CDI, but guidelines acknowledge the lack of compelling evidence. Trials are limited by the use of varying types of strains, numbers of strains, and doses of probiotics, as well the definitions of CDI and CDAD. FMT has been proposed as a method for restoring gut microbiota and has been shown to significantly increase the rate of cure in patients with recurrent CDI. Current studies have demonstrated minimal adverse effects, with no reports of transmission of infectious diseases; however, the optimal delivery method, sample preparation, and donor selection remain unclear. In this review, findings from recent literature are highlighted, and guideline recommendations for the use of these agents in the primary and secondary prevention of CDI are summarized.

Long-term Virologic Suppression Despite Presence of Resistance-associated Mutations Among Perinatally HIV-infected Youth.

BACKGROUND: There is limited information on long-term consequences of continuing combination antiretroviral therapy (cART) consisting of <3 active drugs in treatment-experienced youth with perinatal HIV (PHIV). This study describes the clinical outcomes of PHIV youth who maintained virologic suppression (VS) for ≥1 year despite receiving cART with <3 active agents. METHODS: A retrospective cohort study was conducted to quantify the duration of VS (viral load < 400 copies/mL), and using Cox proportional hazards regression, we identify factors associated with the primary outcome of virologic breakthrough (VB). RESULTS: Thirty-seven patients were included. The median age, baseline CD4 count and HIV RNA viral load were 14 years, 477 cells/mm and 2920 copies/mL, respectively. All patients harbored reverse transcriptase, and 57% harbored protease mutations. The median duration of VS was 37 months (interquartile range: 22-66). Fifteen patients (41%) had VB. The median change in CD4 count during VS was +82 cells/mm at 12 months. The risk of VB was lower in those who gained ≥50 cells/mm by 12 months (unadjusted hazards ratio: 0.271; 95% confidence interval: 0.0825-0.893; P, 0.032); however, this was not significant in the adjusted model. CONCLUSIONS: VS was maintained for a median of 3 years without decline in CD4 count. Independent risk factors for VB were not identified; however, there was a trend toward higher risk of VB in those without CD4 gain of ≥50 cells/mm by 12 months. Suppressive cART containing <3 active agents could be an option in difficult to manage PHIV youth with close monitoring.