Carbapenem-resistant Organisms Research Articles

519. Multidrug-resistant Gram-Negative Bacteremia in Pediatric Patients: Is It Time to Change to Empiric Meropenem?

BackgroundThe rise of antimicrobial resistance among gram-negative (GN) pathogens has been dramatic nationally. Delayed initiation of active antimicrobial agents has been associated with poor outcomes. We aimed at evaluating the prevalence and treatment of multi-drug-resistant gram-negative (MDR-GN) bacteremia in our pediatric patients.MethodsAll episodes of GN bacteremia from 2017–2018 at our institution were retrospectively reviewed. GN defined as MDR in our study were carbapenem-resistant organisms (CRO), extended-spectrum β-lactamase (ESBL) producers, and GN that were resistant to cefepime and ≥2 classes of non-cephalosporin antimicrobial agents. Stenotrophomonas maltophilia was excluded. Ineffective empirical treatment (IET) is defined as an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results.ResultsA total of 292 episodes of GN bacteremia were identified and 6 S. maltophilia were excluded. Of these, 29 bacteremic episodes in 26 patients were caused by MDR-GN organisms including 18 ESBL, 7 CRO, 1 ESBL and CRO, 3 non-ESBL/non-CRO cefepime-resistant MDR-GN. None of the CRO had carbapenemase genes detected. However, there was a patient with multiple sites of infection simultaneously with non-NDM CR Acinetobacter bacteremia and NDM-mediated CR-Klebsiella ventriculitis. The annual rate of MDR-GN bacteremia increased from 8% in 2017 to 12% in 2018. Almost half (48%) of episodes were community onset. Among these, all but one had underlying medical conditions with hospital exposure and most patients had central venous devices at the time of infection. 52% (15/29) episodes of MDR-GN bacteremia had IET. Despite IET, 47% (7/15) had negative blood cultures prior to initiation of effective therapy (6 ESBL and 1 P. aeruginosa). Various antibiotic regimens were used for CRO therapy as shown in Table 1.ConclusionIn our institution, MDR-GN infection is increasing. As such, empiric meropenem is currently recommended in BMT or neutropenic patients with suspected sepsis. However, empiric meropenem must be used judiciously as its widely use will lead to more selection of MDR pathogens. It is essential to continue monitoring of these MDR-GN to guide appropriate empiric regimens. Disclosures All authors: No reported disclosures.

1461. Antimicrobial Susceptibility Patterns of Common Complicated Urinary Tract Infection Pathogens in US Hospitals, 2013–2018

BackgroundIn response to increasing rates of antimicrobial resistance, carbapenems have become first-line treatments for many infections. This, in turn, fosters the potential for resistance (CR). Efforts to mitigate the emergence of CR through carbapenem-sparing strategies must rest on a fundamental understanding of antibiotic resistance patterns among commonly encountered pathogens. Therefore, we examined the microbiology of complicated urinary tract infections (cUTI) in hospitalized patients in the United States.MethodsWe performed a multicenter retrospective cohort study in the Premier database of approximately 180 hospitals, 2013–2018. Using an ICD-9/10-based algorithm we identified all adult patients hospitalized with cUTI and included those with a positive blood or urine culture. Patients with carbapenem-resistant organisms were excluded. We examined the microbiology and susceptibilities to common cUTI antimicrobials (third-generation cephalosporin [C3], fluoroquinolones [FQ], trimethoprim-sulfamethoxazole [TMP/SMZ], fosfomycin [FFM], nitrofurantoin [NFT], and triple-resistant [TR]) over time.ResultsAmong 28,057 organisms from 23,331 patients, the 3 most common pathogens were E. coli (EC, 41.0%), K. pneumoniae (KP, 12.1%), and P. aeruginosa (PA, 11.0%). Among these organisms, resistance to C3 was 10.4% among PA, 12.6% KP and 48.9% EC. EC was most likely to exhibit resistance to all agents of interest, and demonstrated the highest resistance rate to TMP/SMZ (61.5%), and lowest to NFT (10.4%). In contrast, KP had the highest rate of resistance to NFT (27.9%) and lowest to FQ (4.9%). The lowest rate of resistance among PA was to TMP/SMZ (1.9%), and highest to C3 (10.4%). The prevalence of TR in 2013–2014 and 2017–2018, respectively, was 34.2% and 37.4% for EC, 11.8% and 14.2% for KP, and 7.0% and 4.6% for PA.ConclusionAmong the most common pathogens isolated in hospitalized patients with cUTI, and particularly in EC, high and increasing single resistance and TR rates to common antimicrobials were evident, Current empiric treatment strategies may be insufficient against the growing threat of TR.Disclosures All authors: No reported disclosures.

2208. Development and Evaluation of Predictive Models for Estimating Infection Susceptibility to Empiric Treatment Regimens Among Patients with Pneumonia in Intensive Care Units

BackgroundPredictive models for empiric antibiotic prescribing often estimate the probability of infection with multidrug-resistant organisms. In this work, we developed models to predict coverage of specific treatment regimens to better target antibiotics to high- and low-risk patients.MethodsWe established a retrospective cohort of adults admitted to the ICU in a 1,300-bed teaching hospital from November 1, 2011 to June 30, 2016. We included patients with a diagnosis of pneumonia and positive respiratory culture collected during their ICU stay. We collected demographics, comorbidities, and medical history from the electronic health record. We evaluated three penalized regression methods for predicting infection susceptibility to 11 treatment regimens: least absolute selection and shrinkage operator (LASSO), minimax concave penalty (MCP), and smoothly clipped absolute deviation (SCAD). We developed models for susceptibility prediction at two stages of the diagnostic process: for all pathogenic bacteria and for infections with Gram-negative organisms only. We selected final models based on higher area under the receiver operating characteristic (AUROC), acceptable goodness of fit, lower variability of the AUROCs in the cross-validation run, and fewer predictors.ResultsAmong 1,917 cases of pneumonia, 54 different pathogens were identified. The most frequently isolated organisms were: Pseudomonas aeruginosa (16.6%), methicillin-resistant Staphylococcus aureus (16.1%), and Staphylococcus aureus (13.5%). Frequently selected variables included age, Elixhauser score, tracheostomy status, recent antimicrobial use, and prior infection with a carbapenem-resistant organism. All final models used MCP or SCAD methods. Point estimates for the AUROCs in the training set ranged from 0.70 to 0.80, and estimates in the internal validation set ranged from 0.64 to 0.77.ConclusionMCP and SCAD outperformed LASSO. For some regimens, models predicted infection susceptibility with fair accuracy. These models have potential to help antibiotic stewardship efforts to better target appropriate antibiotic use.Disclosures All authors: No reported disclosures.

510. Exposure Investigation Following a Confirmed Case of Candida auris and Multiple Carbapenemase-Producing Carbapenem-Resistant Organisms

BackgroundCo-infections of Candida auris and carbapenemase-producing carbapenem-resistant Gram-negative organisms (CP-CRO) are an increasing global concern and rarely seen in the United States. We report the case of a 59-year-old male, with recent hospitalization in India, admitted to our facility with C. auris isolated from urine and axilla/groin specimens and CP-CRO from five body sites.MethodsTravel screening in the emergency department identified a patient at high risk for colonization/infection with multidrug-resistant organisms (MDRO). Contact precautions were initiated. Eight CP-CRO isolates were subsequently identified from clinical and routine surveillance cultures from five separate sites. Of the isolates, seven contained one or more carbapenemase-producing genes detected by Xpert Carba-R assay (Cepheid, Sunnyvale, CA) (Table 1). The microbiology laboratory alerted the infection control department of a presumptive positive C. auris from a clinical urine culture from the same patient. Enhanced mitigation strategies were initiated in regards to cleaning and disinfection.An exposure investigation was also conducted using a point prevalence approach. Surveillance cultures were obtained from inpatients currently admitted to the same unit as the index patient. Axilla/groin specimens were collected for C. auris testing, and rectal specimens were collected for CP-CRO gene testing (CRE Real-Time PCR).ResultsEighteen patients in addition to the index patient were hospitalized on the acute medicine unit. One patient refused testing for CP-CRO; therefore, 17 patients were tested for CP-CRO, and 18 patients were tested for C. auris. Neither CP-CRO nor C. auris were recovered from any patient.ConclusionA patient co-infected with C. auris and multiple CP-CRO was identified by clinical and routine surveillance cultures at Johns Hopkins Hospital. Travel screening allowed proactive isolation upon presentation. Enhanced infection control measures were implemented and a point prevalence surveillance study was conducted on the general acute care medicine inpatient unit. No transmission of either C. auris or CP-CRO was detected, likely due in part to rapid identification and strict infection control measures. Disclosures All authors: No reported disclosures.

1534. Polymyxin Antimicrobial Susceptibility (AST) Testing and Breakpoints for P. aeruginosa, A. baumannii, and Enterobacteriaceae: Recommendations from the United States Committee on Antimicrobial Susceptibility Testing (USCAST)

BackgroundPolymyxins are important antimicrobial agents for the treatment of infections due to carbapenem-resistant and other multidrug-resistant organisms. Recently, the CLSI and EUCAST have set breakpoints for colistin (EUCAST and CLSI) and polymyxin B (CLSI) with slight differences in recommendations. However, there are issues unique to the polymyxin class that warrant additional guidances. Herein, we assess data related to breakpoint setting and make additional recommendations for polymyxin AST interpretive criteria.MethodsData sources included longitudinal (2011–2017) US surveillance reference broth microdilution (BMD) MIC distributions (128,573 isolates) for colistin and polymyxin B (PB), published data on accuracy of various AST methodologies, in vivo pharmacokinetic/pharmacodynamic (PK-PD) models, prior polymyxin guidelines and agency package insert dosing recommendations, and population PK-PD and toxicodynamic (TD) data. Epidemiological cut-off, PK-PD (and TD), and clinical data were all considered for susceptible (S) breakpoint determinations.ResultsData demonstrate that the most commonly utilized AST methodologies (disk diffusion, Etest, and automated MIC susceptibility panels), as well as agar dilution testing cannot reliably detect resistance; and BMD is the preferred AST. Importantly, colistin S is a reliable surrogate for PB S with cross-S accuracy at > 99% of isolates in each pathogen group. Breakpoint recommendations can be found in the Table with emphasis on applying combination therapy. Key recommendations include an S breakpoint of ≤2 mg/L for each pathogen (both colistin and PB). However, based on a lack of preclinical efficacy in murine pneumonia models, PK/PD concerns, and poor clinical outcome data, we strongly suggest that no breakpoints are applied for pneumonia and that alternative therapies should be used where available. Additionally, due to a lack of significant renal excretion, PB will also have no S breakpoint recommendation for lower urinary tract infections.ConclusionThe polymyxins have compromising characteristics that make them suboptimal antimicrobials when used alone, and additional caveats are required for AST breakpoint interpretive criteria and stewardship programs. Disclosures All authors: No reported disclosures.

2175. Rapid Detection of Carbapenemase Producing Organisms Directly from Blood Cultures Positive for Gram-Negative Bacilli

BackgroundThe rapid detection of carbapenemase-producing organisms (CPOs) directly from blood cultures (BC) positive for Gram-negative bacilli (GNB) may accelerate the appropriate treatment of at-risk patients. Our objective was to evaluate the performance of two commercial assays in the rapid detection of CPOs directly from BC positive for GNB.MethodsBC positive for GNB, taken from patients within the Calgary Health Zone over a 3 month period, were tested for the presence of CPOs with βCARBA® and NG-Test® CARBA 5. A subset of sterile BC samples was seeded with multi-drug-resistant (MDR) GNB. BC were incubated using the Bact-Alert™ system. Positive BC from clinical and seeded samples was tested directly with βCARBA and CARBA 5 from BC pellets processed for direct testing using an ammonium chloride lysis and wash method. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated with 95% confidence intervals for binomial proportions.Results65 samples were tested (30 clinical, 35 seeded). Seeded samples included 1 GES, 4 IMP, 6 KPC, 1 co-producing KPC and NDM, 9 OXA, 4 VIM, 5 NDM, and 5 non-CPO carbapenem-resistant organisms. βCARBA had a sensitivity, specificity, NPV and PPV of 100% (88.4% - 100%), 65.7% (47.8–80.9%), 100%, and 71.4% (61.3%–79.8%), respectively. CARBA 5 had a sensitivity, specificity, NPV and PPV of 90.0% (73.5%–97.9%), 100% (90.0%–100%), 92.1% (80.0%–97.2%), and 100%. When excluding GES, which is known not to be detected by CARBA 5, sensitivity and NPV increased to 93.1% (77.2%–99.2%) and 93.1% (78.0%–98.1%), respectively. False negatives for βCARBA occurred with 1 VIM-1 and IMP-14.ConclusionThis study demonstrates that the detection of CPOs directly from positive BC can be accurately achieved. βCARBA had excellent sensitivity but suffered from poor specificity. CARBA 5 had good sensitivity and specificity but is unable to detect certain CPOs. Testing positive BC directly using βCARBA and/or CARBA 5 may be useful in rapidly detecting CPOs. Results of direct testing from the CARBA5 assay would quickly identify patients amenable to treatment with avibactam combination compounds.Disclosures All authors: No reported disclosures.

Efficacy of ceftazidime/avibactam in monotherapy or combination therapy against carbapenem-resistant Gram-negative bacteria: A meta-analysis

Clinicians may use ceftazidime/avibactam in combination with other active agents to treat infections due to carbapenem-resistant organisms, although no conclusive data support this practice. This meta-analysis compared the efficacy of ceftazidime/avibactam as monotherapy or combination therapy against infections due to carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPa). An online literature search was conducted to identify observational studies published as full papers and indexed up to February 2019 comparing the efficacy, in terms of mortality and microbiological cure rates, of ceftazidime/avibactam monotherapy or combination therapy with other active agents for infections due to CRE or CRPa. The relative risk (RR) of mortality and microbiological eradication was estimated based on pooled data from all eligible studies. Eleven studies were included in the meta-analysis accounting for 396 subjects, of whom 202 received combination therapy. The mortality rate was 38.1% for combination therapy and 30.9% for monotherapy (RR = 1.18, 95% CI 0.88-1.58; P = 0.259). Similarly, no difference was found between the two groups when analysing the rate of microbiological cure (64.9% for combination therapy vs. 63.4% for monotherapy; RR = 1.04, 95% CI 0.85-1.28, P = 0.705). Moreover, no difference was observed for both outcomes when patients infected with P. aeruginosa were excluded from the analysis. This meta-analysis suggests that use of ceftazidime/avibactam in monotherapy or combination therapy for infections due to CRE or CRPa could show a similar effect on mortality and microbiological cure rates. Studies on larger samples are needed to address this important issue.

Characterisation of carbapenem-resistant Gram-negative organisms from clinical specimens in Yola, Nigeria.

This study aimed to identify carbapenem-resistant Gram-negative bacteria from clinical specimens of patients in Yola, Nigeria. Routine clinical specimens were screened for the presence of carbapenem-resistant Gram-negative bacteria using chromogenic agar plates. Susceptibility of all presumptive isolates to carbapenems was tested by MIC and disk diffusion methods. Real-time PCR was used to test for the presence of carbapenemase genes. Screening of 1741 clinical specimens yielded 119 (6.8%) presumptive carbapenem-resistant Gram-negative bacteria. Antimicrobial susceptibility testing confirmed carbapenem resistance in 105 of these isolates. New Delhi metallo-β-lactamase (blaNDM) gene was detected in 26 isolates and Verona integron-encoded metallo-β-lactamase (blaVIM) gene was detected in four. The mechanism of resistance could not be identified in approximately two thirds of the carbapenem-resistant isolates. While blaNDM and blaVIM accounted for 28.6% of the resistance seen, further molecular-based studies are needed to characterise the other mechanisms of carbapenem resistance in these isolates.

Strategic Trials to Define the Best Available Treatment for Neonatal and Pediatric Sepsis Caused by Carbapenem-resistant Organisms.

The optimal standard of care for carbapenem-resistant bloodstream infections in children is currently unknown. This systematic review, aiming to define the best available treatments to be compared with new antibiotics in clinical trials, clearly points out the paucity of available data. The simplification and a wider harmonization of study design are a global priority to inform the best strategies to treat these life-threatening infections in children.

Creating Meaningful Meetings: A Rural Health Approach for Engagement in Antimicrobial Stewardship and Multidrug Resistant Organism Tracking

BACKGROUND In response to the Center for Disease Control and Prevention's (CDC) Antibiotic Resistance Threats Report in 2013, the National Strategy for Combating Antibiotic-Resistant Bacteria provided recommendations to decrease the burden of multi-drug resistant organisms (MDROs). These recommendations included support for antimicrobial stewardship (AMS) programs across settings as well as improved surveillance of MDROs. Our goal was to set up regional meetings to 1) engage healthcare providers from diverse, rural settings on AMS and infection prevention topics and provide a forum for collaboration; 2) encourage submission of carbapenem-resistant organisms (CROs) and antibiogram data to the state laboratory; 3) identify opportunities for goal-setting and allocation of state-level resources. METHODS A Quality Innovation Network-Quality Improvement Organization collaborated with three programs within the state Department of Health (Healthcare Associated Infection (HAI), Medicare Beneficiary Quality Improvement Program (MBQIP) and the Bureau of Laboratories) to hold a series of four face-to-face, cross-setting regional meetings. Meeting satisfaction was evaluated by a brief on-site survey. CRO sample and antibiogram submissions were tracked before and after the meetings. Meeting discussions were documented and grouped by topic. RESULTS Four regional meetings were completed between April-September, 2018 with 103 attendees representing 21 hospitals, 17 long-term care facilities and 6 ambulatory settings. Overall participant satisfaction was 4.35/5. The number of CRO isolates that were tested in our state laboratory increased by 200% and the number of organizations that agreed to submit antibiogram data increased from three to 10 (233% increase) following the events. Major areas of concern identified by participants were: 1) care transitions; 2) physician AMS education; 3) public education on MDRO risk and the role of AMS. CONCLUSIONS Regional meetings that uniquely align infection prevention, pharmacy and laboratory are a highly effective forum to promote cross-setting engagement and collaboration in a rural state with limited resources.

Clinical Soil Removal from Flexible Endoscopes Is Critically Dependent on the Completeness of the Manual Cleaning Process

BACKGROUND Multiple outbreaks of carbapenem-resistant enterobacteriaceae (CRE) and other multi-drug resistant organisms (MDROs), have been associated with flexible endoscopes resulting in unacceptable patient mortality and morbidity. Evidence highlights the importance of effective cleaning to achieve effective high-level disinfection (HLD). The objective of this study is to quantify clinical soil removal from endoscopes through manual cleaning. METHODS This simulated-use study (85 individual trials) measured adenosine-triphosphate (ATP) and protein levels found in the suction/biopsy channel of OlympusTJF-160F duodenoscopes inoculated with an artificial test soil, after partial and complete manual cleaning. Three partial manual cleaning modes of critical importance were identified for the study: 1) incomplete brushing of the suction/biopsy channel, 2) omitting aspiration of the suction/biopsy channel, 3) cleaning an endoscope where soil dried for 24 hours. Analysis used one-way ANOVAs to determine statistical differences. p-values RESULTS Elevated ATP levels above the cleanliness criterion value of 200 relative light units (RLUs) (M.J. Alfa, et al.; AJIC; 41; (2013); 245-248 and 249-253; ANSI/AAMI ST91:2015) were detected for all the partial cleaning modes studied when compared to complete cleaning (p-value CONCLUSIONS This study highlights the importance of complete manual cleaning and finds that incomplete cleaning of duodenoscopes results in 6 to 14 times larger amounts of residual soil. Protein is not detected in partially cleaned duodenoscopes when ATP clearly indicates elevated amounts of remaining soil. The methodology and results of this study can be used to establish a better cleanliness criterion for monitoring the effectiveness of manual cleaning.

Impact of specific inhibitors on metallo-β-carbapenemases detected in Escherichia coli and Klebsiella pneumoniae isolates

Carbapenems are widely regarded as the drugs of choice for the treatment of severe infections caused by extended-spectrum beta lactamases producing Enterobacteriaceae. The emergence of carbapenem-resistant organisms is worrisome due to the limited treatment options. Detection of carbapenemase-producing bacteria is critical for the choice of appropriate therapy. However, Inhibition of carbapenemases is an alternative approach to combat resistance to carbapenms.In this study, Escherichia coli and Klebsiella pneumoniae carbapenem resistant isolates were recovered from 300 clinical isolates. They were subjected phenotypically for detection of class B metallo-carbapenemase (MBL) producers (by carbapenem disks with or without EDTA), and were subjected for confirmation genotypically by PCR. In addition, the synergistic activities of MBL-inhibitors in combination with carbapenems were elucidated.Two E. coli and 15 K. pneumoniae isolates were carbapenem resistant. The genes encoding blaNDM-1 carbapenemase were detected in 16/17 isolates solely, or collaboratively with either blaVIM, or blaIMP or both in all carbapenem resistant isolates, by PCR method. The VIM-carbapenemase was encoded by one isolate. In pre-clinical trials for development of MBL-specific inhibitors, Sub-inhibitory concentrations of citric acid, malic acid, ascorbic acid and ciprofloxacin in combination with imipenem or meropenem exerted synergistic activities against metallo-carbapenemases. Their activities are probably attributed to the chelation of zinc ions in the active site of carbapenemase.Conclusively, these promising combined therapies might represent a new strategy for combating such serious infections caused by metallo-B-carbapenemase producers of K. pneumoniae and E. coli isolates.

Effectiveness and safety of carbapenem antimicrobial management

Objective To investigate the effectiveness and safety of carbapenem antimicrobial management programs (ASP). Methods 671 patients who were discharged from the emergency department of the hospital from January 2017 to April 2018 were enrolled. These patients were subject to before-and-after self-control studies, using such intervention measures as MDT proactive management-feedback-training. January-September of 2017 was set as the pre-intervention stage, and September 2017-April 2018 as the post-intervention stage. The two stages were compared in such indicators as the monthly antibacterial use, quality of care and hospital acquired infection. Results Thanks to the ASP measure against antibiotics like carbapenems, the use rate of carbapenems at the emergency department ward fell from 36.7% to 18.6%, the defined drug doses (DDDs) of carbapenems fell from 211.92 to 82.22, and the antibiotics use density (AUD) of carbapenems fell from 29.18 DDDs/100 day/patient to 11.56. The pathogen detected rate increased significantly (0.61±0.08 versus 0.78±0.16), with a difference of statistical significance (P=0.020). On the other hand, the mean days of stay, average cost per hospitalization, proportion of antibiotics use, incidence of hospital acquired infections, and the infection/colonization rate of carbapenem-resistant organisms (CROs) present no significant changes. There was a moderate positive correlation between carbapenem DDDs and mean days of stay (P=0.034), and also a moderate positive correlation between hospital acquired infection incidence and CROs infection/colonization rate (r=0.545, P=0.029). Conclusions The carbapenem ASP at the hospital proves safe and effective. CROs infection/colonization may be the cause of hospital acquired infection. Prevention and control against multi-drug resistant bacteria on the basis of ASP may add to the effect of ASP. Key words: Anti-bacterial agents; Carbapenem; Effectiveness; Safety; Multidrug-resistant organisms

Advances in Diagnostic Testing that Impact Infection Prevention and Antimicrobial Stewardship Programs.

The primary purpose of this review is to provide a summary of new and emerging laboratory technologies and testing platforms that impact infection prevention and antimicrobial stewardship programs. This review also summarizes available data describing the clinical impact of implementing these new technologies. While there is ample evidence that rapid organism identification technologies for positive blood cultures can ameliorate antimicrobial utilization, an assay that also provides expedited antimicrobial susceptibility testing results is now available and its clinical impact is under investigation. For C. difficile infection diagnosis, data related to performance and impact of "ultrasensitive" toxin assays is emerging in the literature although their role in C. difficile infection diagnosis remains unclear. For hospital-acquired pneumonia, a variety of rapid, automated, multiplexed, "pneumonia" panels have become commercially available and may impact surveillance definitions for ventilator-associated events. Finally, recent FDA clearance of various biochemical and molecular carbapenemase detection tests will facilitate rapid characterization of carbapenem-resistant organisms. Innovations in infectious diseases diagnostics have been making swift strides, broadening diagnostic scope; increasing accuracy and sensitivity; and reducing turnaround time. Many of these innovations directly impact infection prevention and antimicrobial stewardship operations. Close collaboration between infection control, antimicrobial stewardship, and the microbiology laboratory is necessary to ensure that new tests improve patient outcomes.

Antimicrobial-resistant Gram-negative colonization in infants from a neonatal intensive care unit in Thailand

SummaryAntimicrobial-resistant Gram-negative bacteria are a major cause of morbidity and mortality in hospitalized neonates in South and South-East Asia. This study aimed to determine the dynamics of colonization with antimicrobial-resistant Gram-negative bacteria amongst patients in a neonatal intensive care unit (NICU) in Thailand. From 97 enrolled patients, 52% were colonized by an extended-spectrum β-lactamase (ESBL) organism at some point during their stay and 64% were colonized by a carbapenem-resistant organism. Rapid acquisition of ESBL-positive and carbapenem-resistant organisms was found. Once colonized with an antibiotic-resistant organism, patients remained colonized for the remainder of their NICU stay.

Carbapenem resistant organisms: A 9-year surveillance and trends at Saint George University Medical Center

IntroductionCarbapenem resistant organisms (CRO) constitute a large group of bacteria with different mechanisms of resistance and recently increasing global incidence. This rise has ambiguous dynamics and essential local epidemiologic data is lacking. Materials and methodsIn this retrospective study at the 400-bed Saint George Hospital (SGH) in Beirut, Lebanon, we retrieved electronic laboratory records of all intrinsic and acquired CRO isolates from January 1, 2010 until June 30, 2018. Isolation density was calculated as: number of isolates/1000PD. Analysis carried out using WHOnet with a trend time series analysis. ResultsDuring the study period, a total of 2150 non-duplicate CRO were isolated. While Acinetobacter baumanii (AB), Pseudomonas aeruginosa (CRPa), and Stenotrophomonas maltophilia (Sm) constituted 85% of total CRO in the study period, the carbapenem resistant enterobacteriaceae (CRE) rose from few sporadic cases before 2016 to a solid 32% of total CRO in 2018. Our most concrete trends were as follows. The rate of AB bacteremia was at an average of 0.114/1000 PD from 2011 to 2014. In 2015, a sudden doubling of AB bacteremia to 0.23/1000 PD. In 2017, there was a significant decrease to 0.113/1,000PD (p < 0.0001) to reach 0.097/1000PD in 2018 with a continuously declining trend. The peak of Sm bacteremia was in 2016 at 0.121/1000PD after which it significantly decreased by 21% in 2017 to disappear in 2018 (p < 0.0001). There were no significant trends observed in the isolation density of the CRPa group from 2010 until June 2018. Klebsiella pneumonia (CRKp) bacteremia was isolated first in 2013, then in 2016 and continued to rise (p = 0.028). In 2017, carbapenem resistant KP bacteremia rate doubled to 0.05/1,000PD from 0.024/1000 (p = 0.0139). ConclusionIn conclusion, this 9-year study at SGH depicts the major trends and dynamics of local CRO isolation, mainly A. baumanii, P. aeruginosa and CRKp. Further efforts are warranted both locally and internationally for a richer understanding of this trend. Bearing in mind that understanding antimicrobial resistance is a complex, multifaceted process that is only feasible when all its aspects are combined: molecular, phenotypic and clinical.

Predicting probability of perirectal colonization with carbapenem-resistant Enterobacteriaceae (CRE) and other carbapenem-resistant organisms (CROs) at hospital unit admission.

Targeted screening for carbapenem-resistant organisms (CROs), including carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing organisms (CPOs), remains limited; recent data suggest that existing policies miss many carriers. Our objective was to measure the prevalence of CRO and CPO perirectal colonization at hospital unit admission and to use machine learning methods to predict probability of CRO and/or CPO carriage. We performed an observational cohort study of all patients admitted to the medical intensive care unit (MICU) or solid organ transplant (SOT) unit at The Johns Hopkins Hospital between July 1, 2016 and July 1, 2017. Admission perirectal swabs were screened for CROs and CPOs. More than 125 variables capturing preadmission clinical and demographic characteristics were collected from the electronic medical record (EMR) system. We developed models to predict colonization probabilities using decision tree learning. Evaluating 2,878 admission swabs from 2,165 patients, we found that 7.5% and 1.3% of swabs were CRO and CPO positive, respectively. Organism and carbapenemase diversity among CPO isolates was high. Despite including many characteristics commonly associated with CRO/CPO carriage or infection, overall, decision tree models poorly predicted CRO and CPO colonization (C statistics, 0.57 and 0.58, respectively). In subgroup analyses, however, models did accurately identify patients with recent CRO-positive cultures who use proton-pump inhibitors as having a high likelihood of CRO colonization. In this inpatient population, CRO carriage was infrequent but was higher than previously published estimates. Despite including many variables associated with CRO/CPO carriage, models poorly predicted colonization status, likely due to significant host and organism heterogeneity.

Prevalence of ‘Superbugs’, the Carbapenem Resistant Gram Negative Organisms in a Tertiary Care Hospital

Prevalence of ‘Superbugs’, the Carbapenem Resistant Gram Negative Organisms in a Tertiary Care Hospital

Defining the Role of Novel β-Lactam Agents That Target Carbapenem-Resistant Gram-Negative Organisms.

With the current carbapenem-resistant organism crisis, conventional approaches to optimizing pharmacokinetic-pharmacodynamic parameters are frequently inadequate, and traditional salvage agents (eg, colistin, tigecycline, etc) confer high toxicity and/or have low efficacy. However, several β-lactam agents with activity against carbapenem-resistant organisms were approved recently by the US Food and Drug Administration, and more are anticipated to be approved in the near future. The primary goal of this review is to assist infectious disease practitioners with preferentially selecting 1 agent over another when treating patients infected with a carbapenem-resistant organism. However, resistance to some of these antibiotics has already developed. Antibiotic stewardship programs can ensure that they are reserved for situations in which other options are lacking and are paramount for the survival of these agents.

Reversal of carbapenem-resistance in Shewanella algae by CRISPR/Cas9 genome editing

Antibiotic resistance in pathogens is a growing threat to human health. Of particular concern is resistance to carbapenem, which is an antimicrobial agent listed as critically important by the World Health Organization. With the global spread of carbapenem-resistant organisms, there is an urgent need for new treatment options. Shewanella algae is an emerging pathogen found in marine environments throughout the world that has increasing resistance to carbapenem. The organism is also a possible antibiotic resistance reservoir in humans and in its natural habitat. The development of CRISPR/Cas9-based methods has enabled precise genetic manipulation. A number of attempts have been made to knock out resistance genes in various organisms. The study used a single plasmid containing CRISPR/Cas9 and recE/recT recombinase to reverse an antibiotic-resistant phenotype in S. algae and showed blaOXA-55-like gene is essential for the carbapenem resistance. This result demonstrates a potential validation strategy for functional genome annotation in S. algae.