Antipseudomonal Carbapenems Research Articles

Antimicrobial resistance in bacterial wound, skin, soft tissue and surgical site infections in Central, Eastern, Southern and Western Africa: A systematic review and meta-analysis.

Antimicrobial resistance (AMR) is a major global threat and AMR-attributable mortality is particularly high in Central, Eastern, Southern and Western Africa. The burden of clinically infected wounds, skin and soft tissue infections (SSTI) and surgical site infections (SSI) in these regions is substantial. This systematic review reports the extent of AMR from sampling of these infections in Africa, to guide treatment. It also highlights gaps in microbiological diagnostic capacity. PubMed, MEDLINE and Embase were searched for studies reporting the prevalence of Staphylococcus aureus, Eschericheria coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii in clinically infected wounds, SSTI and SSI in Central, Eastern, Southern or Western Africa, and studies reporting AMR from such clinical isolates. Estimates for proportions were pooled in meta-analyses, to estimate the isolation prevalence of each bacterial species and the proportion of resistance observed to each antibiotic class. The search (15th August 2022) identified 601 articles: 59 studies met our inclusion criteria. S. aureus was isolated in 29% (95% confidence interval [CI] 25% to 34%) of samples, E. coli in 14% (CI 11% to 18%), K. pneumoniae in 11% (CI 8% to 13%), P. aeruginosa in 14% (CI 11% to 18%) and A. baumannii in 8% (CI 5% to 12%). AMR was high across all five species. S. aureus was resistant to methicillin (MRSA) in >40% of isolates. E. coli and K. pneumoniae were both resistant to amoxicillin-clavulanic acid in ≥80% of isolates and resistant to aminoglycosides in 51% and 38% of isolates respectively. P. aeruginosa and A. baumannii were both resistant to anti-pseudomonal carbapenems (imipenem or meropenem) in ≥20% of isolates. This systematic review found that a large proportion of the organisms isolated from infected wounds, SSTI and SSI in Africa displayed resistance patterns of World Health Organisation (WHO) priority pathogens for critical or urgent antimicrobial development.

Leuconostoc lactis Bacteremia and Neutropenic Fever

Abstract The epidemiology of bacteremic infections in neutropenic patients has shifted from a previous majority involving gram-positive cocci to an increasing preponderance of gram-negative Enterobacteriaceae species and Pseudomonas aeruginosa. Recommended empiric antimicrobial treatment regimens include an antipseudomonal β-lactam or carbapenem agent while considering risk factors for the possibility of extended-spectrum β-lactamase– or carbapenemase-producing organisms. The addition of vancomycin is generally reserved for the chance of gram-positive cocci infection, principally in patients with central intravascular catheters or soft tissue infections. Persistent or breakthrough bacteremia despite receiving this glycopeptide drug should prompt the clinician to contemplate not only the possibility of vancomycin-resistant enterococci, but also other organisms that possess intrinsic resistance vancomycin, including Leuconostoc species.

Prevalence and molecular analysis of antibiotic resistance of Pseudomonas aeruginosa isolated from clinical and environmental specimens in Basra, Iraq.

The steady increase in the spread of multidrug-resistant Pseudomonas aeruginosa (MDR) has become a major threat to the global health systems, including Iraq. This study aimed to investigate the prevalence and the molecular basis of antibiotic resistance in Pseudomonas aeruginosa isolated from clinical and environmental samples. Pseudomonas aeruginosa strains were identified by standard microbiological procedures followed by PCR confirmation. Antibiotic susceptibility testing, for 16 antimicrobials, was conducted according to the Clinical and Laboratory Standard Institute (CLSI) standardized by disk diffusion and VITEK 2 methods. Detection of beta-lactamases (ESBLs, AmpC and carbapenemase) activities and related encoding genes was performed by using phenotypic methods and PCR technique respectively. A total of 81 clinical specimens and 14 environmental samples were positive for P. aeruginosa. Antimicrobial susceptibility test showed high rates of resistance to antipseudomonal cephalosporines (74.74 to 98.95%), aztreonam (82.11%), antipseudomonal carbapenems (68.4%), piperacillin/tazobactam (69.5%) ciprofloxacin (71.6%), and aminoglycosides (69%), with emergence of resistance to colistin (7.4%) among tested P. aeruginosa. Among the tested isolates, 69 (72.63%) strains were MDR, of which 63 (91.3%) strains were extremely drug resistance (XDR). Most of the isolated strains harbored one or more of ESBL genes (bla SHV-2a, bla CTX-M-28, bla VEB-2, bla OXA-677, bla PER) with predominant bla OXA-677, but none of the MBLs (GIM, SIM, SPM, IMP) and AmpC (FOX) genes were detected. The results highlighted a high prevalence rate of MDR and XDR and emergence of colistin resistance P. aeruginosa at Basra hospitals, Iraq.

950. Impact of the COVID 19 pandemic on antimicrobial stewardship program, broad-spectrum antibiotics consumption and Clostridioides difficile diarrhea incidence

Abstract Background The aim was to evaluate the impact of the COVID 19 pandemic on the antimicrobial stewardship program of our hospital, analyze changes in broad-spectrum antibiotics consumption, and analyze the evolution of the incidence of Clostridioides difficile (CD) diarrhea. Methods Database with the following variables was created: monthly percentage of broad-spectrum antibiotic prescriptions that were evaluated by the antimicrobial stewardship team (AMST), monthly consumption of antimicrobials and monthly incidence of diarrhea due to CD. Pre-pandemic period was considered from March 1th, 2018 to February 29th, 2020 and the pandemic period from March 1th, 2020 to February 28th, 2022. Time series analysis was performed with ARIMA models to assess the association of the pandemic period with a change in the monthly activity of AMST, in the monthly antibiotic consumption, and in the monthly incidence of CD diarrhea. The correlation of the percentage of monthly broad-spectrum antibiotic prescriptions reviewed by AMST with the monthly broad-spectrum antimicrobials consumption was also evaluated, using the Spearman coefficient. Results During the pandemic period, there was a significant reduction in monthly percentage of broad-spectrum antibiotic prescriptions reviewed by the AMST (28% vs 82%; P< 0.01). There was a 29% increase in consumption of broad-spectrum antibiotics in the pandemic period (15.7 vs 12.1 DDD per 100 bed-days; P=ns). The following antibiotics showed a significant increase in their consumption: antipseudomonal carbapenems (2 vs 1.4 DDD per bd; P< 0.01), daptomycin (1.8 vs 0.5 DDD per bd; P< 0.01), cefepime (1.1 vs 0.6 DDD per bd; P< 0.01), aztreonam (0.4 vs 0.3 DDD per bd; P=0.04), antibiotics with anti-MRSA activity (35.6 vs 12.9 DDD per bd; P< 0.01). There was a 41% increase in the incidence of nosocomial CD diarrhea (1.02 vs. 0.7 cases per 1000 bd; P=0.03). The percentage of broad-spectrum antibiotic prescriptions reviewed by the AMST correlated well with the consumption of this group of antibiotics (cc -0.63; P< 0.01). Conclusion COVID-19 pandemic has had a significant impact on the antimicrobial stewardship program at our hospital, with an increase in broad-spectrum antimicrobials consumption and a significant increase in the incidence of Clostridioides difficile diarrhea. Disclosures All Authors: No reported disclosures.

Activity of carbapenem antibacterial drugs against Pseudomonas aeruginosa in nosocomial infections

Currently, Pseudomonas aeruginosa is the leading causative agent of nosocomial infections in Russia. Pseudomonas aeruginosa is characterized by a high level of resistance to antibacterial drugs that are used to treat infections in the hospital. To date, the issue of the greatest clinical significance is the growth of resistance of nosocomial isolates to antipseudomonal penicillins and carbapenems, which requires monitoring the level of resistance to antimicrobial agents in this pathogen to optimize the starting regimens of antibiotic therapy. Purpose of the study. To assess the pharmacodynamic parameters of carbapenem antibacterial drugs for nosocomial infections caused by Pseudomonas aeruginosa in the Russian Federation.

Evaluation of Carbapenem Use Before and After Implementation of an Antimicrobial Stewardship-Led Carbapenem-Sparing Strategy in a Lebanese Tertiary Hospital: A Retrospective Study.

PurposeThe use of carbapenem before and after implementation of an antimicrobial stewardship-led carbapenem-sparing strategy at a tertiary care center in Lebanon was evaluated.MethodsA retrospective, observational chart review was performed on all hospitalized pediatric and adult patients who received carbapenem therapy during January 2019 and January 2020. Patients who started their regimen before January or received carbapenems for less than 24 hours were excluded. Primary outcomes included the appropriateness of physician prescribing patterns and pharmacists’ interventions, as well as appropriateness and response rates of the latter. Secondary outcomes included the carbapenem defined daily dose (DDD) and days of therapy (DOT). Descriptive statistics were used in the analysis and a p-value < 0.05 was considered to be statistically significant.ResultsA total of 157 and 150 patients charts were reviewed in January 2019 and January 2020, respectively. There was no difference in baseline characteristics except for inpatient services and rates of isolated multidrug-resistant organisms. When comparing the two timelines, the appropriateness of physicians’ prescribing patterns increased in terms of empirical therapy, targeted therapy, and duration of therapy but the results were not statistically significant. Pharmacists’ interventions significantly increased with regards to the duration of therapy (p= <0.001), dose adjustment (p<0.001), de-escalation to a narrower spectrum antibiotic (p=0.007), and use of extended infusion (p=0.042). The DDD and DOT were higher for ertapenem and lower for anti-pseudomonal carbapenems in January 2020.ConclusionThe carbapenem-sparing strategy adopted by the antimicrobial stewardship program contributed to an increase in the number of interventions made by pharmacists on carbapenem therapy, including their appropriateness, and response rate. Despite an improvement in the physician-prescribing patterns, more awareness and education may be needed to achieve a better impact.

Infective endocarditis of a native aortic valve due to Pseudomonas aeruginosa complicated by progressive multi-drug resistance

Treatment of infective endocarditis secondary to Pseudomonas aeruginosa can be challenging because of this organism's ability to acquire antimicrobial resistance over time. We describe a patient with native aortic valve infective endocarditis due to P. aeruginosa who developed progressive multi-drug resistance while on therapy. The resistance mechanisms were characterized using whole-genome sequencing. We identified two mutations in subsequent isolates (dacB and OprD) that conferred resistance to anti-pseudomonal penicillins, cephalosporins, and carbapenems. The patient was treated with combination high-dose continuous infusion meropenem and ciprofloxacin therapy, in addition to bioprosthetic aortic valve replacement and repair of ventricular septal wall defect. Antibiotics were continued for 6 weeks post-cardiac surgery and the patient remains infection free 18 months post-completion of antibiotic therapy. Clinicians should be aware of the ability of P. aeruginosa to acquire resistance mechanisms in response to selective antibiotic pressures in high-inoculum infections such as infective endocarditis. The mutations identified in this case report correlated well with the evolving antimicrobial resistance profile observed.

An Ulcerating Perineal Rash in an 8-month-old Girl.

An Ulcerating Perineal Rash in an 8-month-old Girl.

Antimicrobial resistance among Enterobacteriaceae, Staphylococcus aureus, and Pseudomonas spp. isolates from clinical specimens from a hospital in Nairobi, Kenya

BackgroundAntimicrobial resistance among pathogens of public health importance is an emerging problem in sub-Saharan Africa. Unfortunately, published information on the burden and patterns of antimicrobial resistance (AMR) in this region is sparse. There is evidence that the burden and patterns of AMR vary by geography and facility. Knowledge of local epidemiology of AMR is thus important for guiding clinical decisions and mitigation strategies. Therefore, the objective of this study was to determine the burden and predictors of AMR and multidrug resistance (MDR) among bacterial pathogens isolated from specimens submitted to the diagnostic laboratory of a hospital in Nairobi, Kenya.MethodsThis retrospective study used laboratory records of 1,217 clinical specimens submitted for bacterial culture and sensitivity testing at the diagnostic laboratory of The Karen Hospital in Nairobi, Kenya between 2012 and 2016. Records from specimens positive for Enterobacteriaceae, Staphylococcus aureus, or Pseudomonas spp. isolates were included for analysis. Firth logistic models, which minimize small sample bias, were used to investigate determinants of AMR and MDR of the isolates.ResultsA total of 222 specimens had bacterial growth. Most Enterobacteriaceae isolates were resistant to commonly used drugs such as penicillin/β-lactamase inhibitor combinations (91.2%) and folate pathway inhibitors (83.7%). Resistance to extended-spectrum cephalosporins was also high (52.9%). Levels of AMR and MDR for Enterobacteriaceae were 88.5% and 51%, respectively. Among S. aureus isolates, 57.1% were AMR, while 16.7% were MDR. As many as 42.1% of the Pseudomonas spp. isolates were aminoglycoside-resistant and 15% were fluoroquinolone-resistant, but none exhibited resistance to antipseudomonal carbapenems. Half of Pseudomonas spp. isolates were AMR but none were MDR. Significant predictors of MDR among Enterobacteriaceae were organism species (p = 0.002) and patient gender (p = 0.024).ConclusionsThe high levels of extended-spectrum cephalosporin resistance and MDR among Enterobacteriaceae isolates are concerning. However, the relatively low levels of MDR S. aureus, and an absence of carbapenem resistance among Pseudomonas isolates, suggests that last-line drugs are still effective against S. aureus and Pseudomonas infections. These findings are relevant for guiding evidence-based treatment decisions as well as surveillance efforts and directions for future research, and contribute to the sparse literature on AMR in sub-Saharan Africa.

Risk Factors for the Acquisition of Enterococcus faecium Infection and Mortality in Patients with Enterococcal Bacteremia: A 5-Year Retrospective Analysis in a Tertiary Care University Hospital.

The incidence of bacteremia caused by Enterococcus faecium, which is highly resistant to multiple antibiotics, is increasing in Japan. However, risk factors for the acquisition of E. faecium infection and mortality due to enterococcal bacteremia are not well known. We compared demographic, microbiological, and clinical characteristics using a Cox regression model and univariate analysis. We performed a multivariate analysis to identify risk factors for patients treated between 2014 and 2018. Among 186 patients with enterococcal bacteremia, two groups included in the Kaplan–Meier analysis (E. faecalis (n = 88) and E. faecium (n = 94)) showed poor overall survival in the E. faecium group (HR: 1.92; 95% confidence interval: 1.01–3.66; p = 0.048). The median daily antibiotic cost per patient in the E. faecium group was significantly higher than that in the E. faecalis group ($23 ($13–$34) vs. $34 ($22–$58), p < 0.001). E. faecium strains were more frequently identified with previous use of antipseudomonal penicillins (OR = 4.04, p < 0.001) and carbapenems (OR = 3.33, p = 0.003). Bacteremia from an unknown source (OR = 2.79, p = 0.025) and acute kidney injury (OR = 4.51, p = 0.004) were associated with higher risks of 30-day mortality in patients with enterococcal bacteremia. Therefore, clinicians should provide improved medical management, with support from specialized teams such as those assisting antimicrobial stewardship programs.

Dissemination of carbapenem-resistant Pseudomonas aeruginosa isolates and their susceptibilities to ceftolozane-tazobactam in Germany

Pseudomonas aeruginosa (PA) is a major cause of healthcare-associated infections. Antipseudomonal carbapenems are among the antimicrobial agents used to treat PA infections, but several mechanisms of resistance, including the production of a carbapenemase (CP), may compromise their clinical efficacy. The objectives of this study were to determine: (i) the dissemination of carbapenem-resistant CP-negative and CP-positive PA isolates; and (ii) the in-vitro activity of ceftolozane-tazobactam (CTT) against carbapenem-susceptible and carbapenem-resistant isolates. Isolates were collected prospectively from January 2016 to April 2017 at 20 German medical laboratories. Each centre was asked to provide 50 consecutive isolates from hospitalized patients. Overall, 985 isolates were collected, of which 34% were obtained from intensive care patients. Seven hundred and thirty-eight (74.9%) isolates were susceptible to both imipenem and meropenem (Subgroup I), and 247 (25.1%) isolates were resistant to carbapenems (Subgroup II): 125 (12.7%) were imipenem-resistant but meropenem-susceptible, 12 (1.2%) were meropenem-resistant but imipenem-susceptible, and 110 (11.2%) were resistant to both carbapenems (Subgroup III). A CP was detected in 28 (2.8%) isolates (predominantly VIM-2). Nine hundred and fifty (96.4%) isolates were CTT-susceptible. Susceptibility to CTT was seen in 99.6% of Subgroup I isolates, 87% of Subgroup II isolates and 74.5% of Subgroup III isolates. Overall, 2.8% of PA produced a CP, while 22.2% were carbapenem-resistant, CP-non-producing isolates. Based on these findings, CTT may be considered for treatment of PA infections, particularly those caused by multi-drug-resistant CP-non-producing isolates.

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) wereidentified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.

Acute Generalized Exanthematius Pustulosis Caused by a Selective Allergy to Imipenem-Cilastatin: A Case Report

Acute generalized exanthematous pustulosis (AGEP) is acute onset of non-follicular, sterile pustules on an erythematous base. AGEP is commonly caused by drugs. A 65-year- woman, who suffered from systemic sclerosis, received 2 weeks of ertapenem and de-escalated to trimethoprim-sulfamethoxazole with good clinical outcome and no adverse reaction. During admission, this patient developed pneumonia and imipenem was initiated while trimethoprim-sulfamethoxazole was discontinued. This patient developed AGEP after 8 days of imipenem therapy and skin eruptions disappeared after imipenem administration finally ceased. This is a case of AGEP due to imipenem and no cross reaction to ertapenem. Nonetheless, re-challenge of other antipseudomonal carbapenems may be used cautiously.

Bacterial membrane vesicles from Acinetobacter baumannii induced by ceftazidime are more virulent than those induced by imipenem

ABSTRACT Patients with Acinetobacter baumannii bacteremia treated with antipseudomonal cephalosporins showed higher 14-day mortality than patients treated with antipseudomonal carbapenems. We hypothesized that the bacterial membrane vesicles (BMVs) induced by antipseudomonal cephalosporins are more virulent than BMVs induced by antipseudomonal carbapenems. To simulate the clinical condition with inadequate antimicrobial treatment, carbapenem-resistant A. baumannii was treated with ceftazidime (an antipseudomonal cephalosporin) or imipenem (an antipseudomonal carbapenem) at 1/2 the minimum inhibitory concentration. BMVs and BMV-carried lipopolysaccharide were measured by nanoparticle tracking analysis and western blotting, respectively. Cytokine expression in RAW264.7 macrophages or mice serum induced by the BMVs was determined by ELISA, fluorescent bead-based immunoassay or western blotting. The virulence of the BMVs was assessed in mice. Liquid chromatography tandem-mass spectrometry was used to determine the protein contents of the BMVs. We found that ceftazidime induced a higher number of BMVs (CAZ-BMV), which carried more LPS, and induced higher expression levels of iNOS, IL-1β, and IL-6 in macrophages, higher expression of many cytokines in mice, more neutrophil infiltration in lung interstitium, and higher mortality in mice than imipenem-induced BMVs (IMP-BMV). When adjusted to same amount of LPS, CAZ-BMV still led to higher mortality than IMP-BMV. Proteomic analysis revealed different protein contents in CAZ-BMV and IMP-BMV. In conclusion, A. baumannii BMVs induced by ceftazidime are more virulent than BMVs induced by imipenem.

Early Broad-Spectrum Antibiotics and Risk of Acute Graft-Versus-Host Disease in Children: An Analysis from the Center for International Blood and Marrow Transplantation Research (CIBMTR) and the Pediatric Health Information System (PHIS)

Background Variation in the gastrointestinal microbiota after hematopoietic cell transplantation (HCT) has been associated with acute graft-versus-host disease (aGVHD). The significant immunosuppression associated with HCT leads to frequent broad-spectrum antibiotic exposures that in turn drive host microbiota composition. We sought to explore the association of different antipseudomonal antibiotic classes, commonly administered as empiric therapy for neutropenic fever, with subsequent aGVHD-risk in a large, multicenter cohort of children undergoing HCT for acute leukemia. We hypothesized that antibiotic classes that retain broad anti-anaerobic activity would increase aGVHD due to the greater potential impact of these agents on the microbiota. Methods Children 1-21 years old who underwent first HCT for acute leukemia from 2004 to 2017 were identified in 2 databases: CIBMTR, an observational database with demographic, transplant and outcomes information, and PHIS, an administrative database with resource utilization data from freestanding children's hospitals. Patients were then merged based on date of birth, date of transplant, sex and disease. The outcome was grade 2-4 aGVHD by day +100. The primary exposures were 3 distinct classes of antibiotics commonly used for empiric therapy: (1) antipseudomonal cephalosporins, (2) antipseudomonal penicillins and (3) carbapenems. They were captured as days of therapy from conditioning start to day +7, and classified as no, low (1-3 days), or high (&amp;gt;3 days) exposure. Logistic regression was applied to evaluate the association between aGVHD and each exposure, controlling for exposure to the other two classes. For the subset of patients with data on date of GVHD onset, a time to event analysis was performed considering death without GVHD as a competing event. For both analyses, we constructed multivariable models that were informed by a directed acyclic graph and included covariates representing demographics, transplant characteristics and GVHD risk factors associated with both exposure and outcome. The adjusted models also included exposure to other antibiotics within the same window, captured as fluoroquinolones, intravenous vancomycin and other adjunctive antibiotics, with and without anti-anaerobic activity. Generalized estimating equations with robust variance estimates were employed to account for clustering at the hospital level. Results The assembled cohort included 2,501 patients at 35 hospitals. One-third of patients (36.6%) developed aGVHD, 4.4% died without GVHD and no patients were lost to follow-up. The proportion of patients exposed to at least 1 day of an antipseudomonal cephalosporin was 52.2%, but was lower for antipseudomonal penicillins (24.1%) and carbapenems (18.2%). Table 1 shows patient characteristics by exposure to the antibiotic classes of interest. The unadjusted and adjusted associations between the three antibiotic classes and aGVHD are shown in table 2. In the unadjusted model, high exposure to cephalosporins and carbapenems was statistically associated with increased aGVHD risk. For antipseudomonal penicillins, the direction of association was the same but not statistically significant. After adjustment, most point estimates reverted towards the null. The time to event analysis included 1,146 patients that were similar to the overall cohort with a similar incidence of aGVHD (35.5%) diagnosed a median of 28 (range: 8-100) days after HCT. This group had a higher proportion of mismatched donors (40.9 vs 30.2%), cord blood transplants (40.0 vs 23.5%) and receipt of growth factors (50.5% vs 38.9%). Table 2 also shows the unadjusted and adjusted associations for this analysis. As above, the unadjusted point estimates of association between cephalosporins and carbapenems and aGVHD were suggestive of an association but reverted towards the null with adjustment. Conclusions After controlling for other antibiotic exposures and GHVD-risk factors, there was not a statistically significant association between antibiotic exposure and aGVHD for any of three antibiotic classes commonly used for empiric therapy. However, the adjusted point estimates suggest exposure to carbapenems may confer some additional aGHVD risk. Further exploration of different exposure windows is planned to understand if the identified associations change with capture of earlier or later antibiotic exposures. Disclosures Jagasia: Kadmon: Consultancy; Incyte: Consultancy; Janssen: Research Funding. MacMillan:Alpine Immune Sciences: Consultancy; Angiocrine: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Equillium: Membership on an entity's Board of Directors or advisory committees. Fisher:Pfizer: Research Funding; Astellas: Other: Data Safety Monitoring Board Chair for an antifungal study; Merck: Research Funding.

482. Time Series Analysis of Antimicrobial Consumption and Pseudomonas aeruginosa Resistance in an Academic Medical Center in the United States (2013–2018)

BackgroundMonitoring antimicrobial use and resistance are key components of initiatives to promote antimicrobial stewardship and prevent antimicrobial-resistant infections. In this surveillance study, we evaluated trends in resistance among healthcare-associated P. aeruginosa isolates and potential associations with antimicrobial consumption.MethodsWe established a retrospective cohort of P. aeruginosa isolates collected ≥48 hours after inpatient admission at a 1,300-bed academic medical center from July 1, 2013 to July 31, 2018. We included isolates from all clinical cultures and retained the first isolate for a patient encounter. We defined the multidrug-resistant (MDR) status in accordance with the phenotype definitions established by the Centers for Disease Control and Prevention. We calculated the monthly percentage of class-specific resistance and MDR status among isolates. We measured monthly antimicrobial consumption as days of therapy per 1,000 patient-days. To evaluate potential associations between identified trends in resistance and antimicrobial use, we constructed autoregressive integrated moving average models (ARIMA) with transfer functions.ResultsOf 1,897 isolates included in the analysis, 303 (16.0%) were classified as MDR P. aeruginosa. The rate of healthcare-associated P. aeruginosa infections and percent of MDR isolates remained stable over the five-year study period. However, we identified trends in resistance to specific antimicrobial classes: there was a significant increase in resistance to antipseudomonal carbapenems, while resistance to aminoglycosides and extended-spectrum cephalosporins decreased. Using the ARIMA modeling strategy, bivariable analyses of resistance and antimicrobial use revealed that carbapenem-resistant P. aeruginosa was positively correlated with the use of antipseudomonal carbapenems at a 1-month lag and ertapenem at a 5-month lag.ConclusionRisk assessments that only measure rates of MDR organisms may miss underlying trends in class resistance. Increasing carbapenem resistance despite a stable proportion of MDR isolates highlights a critical area for continued monitoring and antimicrobial stewardship initiatives targeted at carbapenem use in our hospital. Disclosures All authors: No reported disclosures.

Feasibility of Core Antimicrobial Stewardship Interventions in Community Hospitals

The feasibility of core Infectious Diseases Society of America-recommended antimicrobial stewardship interventions in community hospitals is unknown. To determine the feasibility and results of implementing 2 core stewardship intervention strategies in community hospitals. Three-stage, multicenter, prospective nonrandomized clinical trial with crossover design. The setting was 4 community hospitals in North Carolina (median bed size, 305; range, 102-425). Participants were all patients receiving targeted study antibacterial agents or alternative, nonstudy antibacterial agents. The study dates were October 2014 through October 2015. All statistical analyses were completed as of October 2016. Two antimicrobial stewardship strategies targeted vancomycin hydrochloride, piperacillin-tazobactam, and the antipseudomonal carbapenems on formulary at the study hospitals: (1) modified preauthorization (PA), in which the prescriber had to receive pharmacist approval for continued use of the antibiotic after the first dose, and (2) postprescription audit and review (PPR), in which the pharmacist would engage the prescriber about antibiotic appropriateness after 72 hours of therapy. Two hospitals performed modified PA for 6 months, then PPR for 6 months after a 1-month washout. The other 2 hospitals performed the reverse. The primary outcome was the feasibility of implementing the interventions, determined by (1) approval by hospital administration and committees at each study hospital; (2) completion of pharmacist training; (3) initiation and implementation as determined by number, type, and outcomes of interventions performed; and (4) time required for interventions. Secondary outcomes included antimicrobial use (days of therapy) compared with matched historical periods and length of hospitalization. A total of 2692 patients (median age, 65 years; interquartile range, 53-76 years) underwent a study intervention; 1413 (52.5%) were female, 1323 (49.1%) were white, and 1047 (38.9%) were African American. Intervention approvals took a median of 95 days (range, 56-119 days); during these discussions, strict PA was deemed not feasible. Instead, the modified PA intervention was used throughout the study. Pharmacists performed 1456 modified PA interventions (median per hospital, 350 [range, 129-628]) and 1236 PPR interventions (median per hospital, 298 [range, 273-366]). Study antimicrobials were determined to be inappropriate 2 times as often during the PPR period (41.0% [435 of 1060] vs 20.4% [253 of 1243]; P < .001). Pharmacists recommended dose change more often during the modified PA intervention (15.9% [232 of 1456] vs 9.6% [119 of 1236]; P < .001) and de-escalation during PPR (29.1% [360 of 1236] vs 13.0% [190 of 1456]; P < .001). The median time dedicated to the stewardship interventions varied by hospital (range of median hours per week, 5-19). Overall antibiotic use decreased during PPR compared with historical controls (mean [SD] days of therapy per 1000 patient-days, 925.2 [109.8] vs 965.3 [109.4]; mean difference, -40.1; 95% CI, -71.7 to -8.6), but not during modified PA (mean [SD] days of therapy per 1000 patient-days, 931.0 [102.0] vs 926.6 [89.7]; mean difference, 4.4; 95% CI, -55.8 to 64.7). Strict PA was not feasible in the study hospitals. In contrast, PPR was a feasible and effective strategy for antimicrobial stewardship in settings with limited resources and expertise. ClinicalTrials.gov identifier: NCT02212808.

The microbiology of chronic osteomyelitis: Changes over ten years

AimThis study quantified changes in the microbiology of osteomyelitis over a ten year period from a single centre within the UK with regard to infection with multi-drug resistant (MDR) bacteria and susceptibility of antimicrobial regimens. MethodPatients with chronic osteomyelitis undergoing definitive surgery from 2013–2017 were inluded (n = 223). Microbiology was compared to patients in a cohort from 2001–2004, using the same diagnostic criteria, and same deep tissue sampling technique (n = 157). Clinical features associated with MDR bacterial infection were analysed using logistic regression. ResultsBoth cohorts had similar baseline characteristics. Despite a similar proportion of Staphylococcus aureus in both cohorts, the rate of methicillin resistant Staphylococcus aureus (MRSA) infection was lower in 2013–2017 compared to 2001–2004 (11.4% vs 30.8% of Staphylococcus aureus, p = 0.007). However, the proportion of MDR infections was similar in both cohorts (15.2% versus 17.2%). Metalwork was associated with MDR infection (unadjusted OR 5.0; 95% CI: 1.15 to 22.0). There was no change in resistance to glycopeptide / meropenem combination treatment (2.2% vs 2.5%, p > 0.9). ConclusionsIn this centre, rates of MRSA osteomyelitis have fallen by two thirds, over the past 10 years, in line with the reducing rate of MRSA bacteraemia nationally. A history of metalwork may predict MDR infection. A glycopeptide with an anti-pseudomonal carbapenem remains the post-operative empiric systemic regimen of choice. Resistance patterns support the use of a glycopeptide with an aminoglycoside in local antibiotic therapy.

Carbapenem-Resistant Pseudomonas aeruginosa at US Emerging Infections Program Sites, 2015.

Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. During July–October 2015 in the United States, we piloted laboratory-based surveillance for carbapenem-resistant P. aeruginosa (CRPA) at sentinel facilities in Georgia, New Mexico, Oregon, and Tennessee, and population-based surveillance in Monroe County, NY. An incident case was the first P. aeruginosa isolate resistant to antipseudomonal carbapenems from a patient in a 30-day period from any source except the nares, rectum or perirectal area, or feces. We found 294 incident cases among 274 patients. Cases were most commonly identified from respiratory sites (120/294; 40.8%) and urine (111/294; 37.8%); most (223/280; 79.6%) occurred in patients with healthcare facility inpatient stays in the prior year. Genes encoding carbapenemases were identified in 3 (2.3%) of 129 isolates tested. The burden of CRPA was high at facilities under surveillance, but carbapenemase-producing CRPA were rare.

Variation in a novel antipseudomonal antimicrobial consumption metric across hospital inpatient units at a Veterans Affairs hospital: A retrospective cohort study

A novel antimicrobial consumption metric designed to identify the proportion of carbapenem consumption (PoCC) among broad-spectrum antipseudomonal antimicrobials has been shown to vary significantly by US Census Bureau region. This retrospective surveillance study identified significant total PoCC variability (27%; P = .001) across 8 inpatient units from January 2017 through June 2018. This metric may be useful in identifying and comparing inpatient units that may be overusing antipseudomonal carbapenems.