Multidrug-resistant Gram-negative Organisms Research Articles

Predictors and microbiology of ventilator-associated pneumonia among patients with exacerbation of chronic obstructive pulmonary disease.

Background:Understanding the risk factors and microbiology of ventilator-associated pneumonia (VAP) among patients with chronic obstructive pulmonary disease (COPD) is important for the application of preventive and therapeutic interventions. Therefore, this study was planned to assess the clinical predictors and microbiological features of VAP among COPD patients.Materials and Methods:This prospective study involved patients with exacerbation of COPD who required mechanical ventilation and admitted in respiratory intensive care unit at a tertiary care teaching hospital. Various baseline demographic and clinical features were compared between patients with VAP and without VAP. Univariate and multivariable analyses were done to assess the impact of demographic and clinical features on the development of VAP.Results:The study included 100 intubated patients with age (mean ± standard deviation [SD]) of 62.45 ± 8.32 years, duration (median) of COPD of 6 years, and Acute Physiology, Age, and Chronic Health Evaluation score (mean ± SD) of 18.60 ± 4.30. In this cohort, 17 patients developed VAP. Multivariable analysis showed that Sequential Organ Failure Assessment (SOFA) score at admission, re-intubation, and history of previous hospitalization were independent predictors of VAP with odds ratio (95% confidence interval) of 2.70 (1.24, 5.63; P = 0.012), 66.96 (4.86, 922.72; P = 0.002), and 35.92 (2.84, 454.63; P = 0.006), respectively. Acinetobacter baumannii was the most frequent organism (n = 8; 47%), followed by Klebsiella pneumoniae (n = 5; 29%), Pseudomonas aeruginosa (n = 1; 6%), and Enterobacter spp. (n = 1; 6%). All organisms were multidrug resistant (MDR).Conclusions:SOFA score at admission, re-intubation, and history of previous hospitalization were independent predictors of VAP. Antimicrobial therapy for VAP should cover MDR Gram-negative organisms.

1184. Resistance Patterns and Susceptibility Analysis of Klebsiella pneumoniae Infections in Service Members Who Sustained Trauma in Iraq and Afghanistan

Background Klebsiella pneumoniae was the third most common species of multidrug-resistant (MDR) Gram-negative organism in military trauma patients injured in Iraq and Afghanistan (2009–2014). This study aims to characterize the antimicrobial susceptibility and resistance patterns of K. pneumoniae isolates in these patients.MethodsAll infecting K. pneumoniae isolates (IKpI) archived by the Trauma Infectious Disease Outcomes Study (TIDOS) and 96 colonizing isolates (CKpI) from groin swabs were included (6/09-12/14). All CKpI linked with IKpI were included; the remainder to total 50 MDR and 46 non-MDR CKpI were chosen randomly. Antimicrobial identification and susceptibilities were determined by CLSI criteria using the BD Phoenix Automated Microbiology System. MDR was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems, and/or fluoroquinolones or production of an ESBL or KPC.ResultsOf 588 K. pneumoniae archived isolates, 237 isolates were included in the analysis (141 IKpI and 96 CKpI). IKpI sources were 40% wound, 22% respiratory, 20% blood, 9% urine, and 9% other. Antibiotic susceptibilities for IKpI were: cefazolin (CFZ) 20%, ceftriaxone 30%, levofloxacin 62%, piperacillin–tazobactam (PTZ) 41%, meropenem 96%, and amikacin 89%. MDR IKpI and CKpI were more likely to have had prior fluoroquinolone (82% vs. 18%, P < 0.01) or anti-pseudomonal penicillin (53% vs. 47%, P < 0.01) exposure. Seventeen patients had CKpI cultured at a median of 5 days (IQR 2–17) before a subsequent IKpI with 11 (65%) having MDR CKpI. All IKpI isolated after MDR CKpI were also MDR. Among IKpI recovered after non-MDR CKpI, new resistance was noted in 1 IKpI to gentamicin (200 days post-CKpI), 1 IKpI to ertapenem (7 days post-CKpI), two IKpI to CFZ (10 days and 17 days, respectively), and 1 IKpI to PTZ (19 days post-CKpI). Serial isolates of IKpI had similar MDR status (63% initial IKpI were MDR, whereas 76% of subsequent IKpI were MDR).Conclusion K. pneumoniae isolates in military trauma patients from Iraq and Afghanistan had challenging resistance patterns. Prior exposure to fluoroquinolones and anti-pseudomonal penicillins were associated with MDR K. pneumoniae isolation. MDR status of CKpI predicted subsequent IKpI MDR status.Disclosures All authors: No reported disclosures.

1198. Clinical Characteristics and Outcomes of Klebsiella pneumoniae Infections in Service Members Who Sustained Trauma in Iraq and Afghanistan

Background Klebsiella pneumoniae infections present a challenge to the clinician due to increasing resistance. K. pneumoniae was the third most common species of multidrug-resistant (MDR) Gram-negative organism in trauma patients sustaining injuries in Iraq and Afghanistan from 2009 to 2014. This study aims to elucidate the epidemiology of these infections by characterizing clinical aspects, risk for MDR infections, and outcomes.MethodsAll initial and serial (≥7 days from prior isolate) infecting K. pneumoniae isolates were collected from the Trauma Infectious Disease Outcomes Study (TIDOS) (6/09-12/14). Antimicrobial susceptibilities were determined using the BD Phoenix Automated Microbiology System and CLSI criteria. MDR was defined as either resistance to ≥3 classes of aminoglycosides, β-lactams, carbapenems and/or fluoroquinolones or production of an ESBL or KPC.ResultsOf 588 K. pneumoniae isolates in the TIDOS registry, 141 infecting isolates (98 initial) from 51 patients met inclusion criteria. Initial isolates were respiratory (31%), wound (25%), blood (20%), urine (10%), intra-abdominal (8%) and other (6%). All patients were male with a median age of 23 years (IQR 21–28). The majority of patients (82%) suffered blast injuries; of which, 88% were from improvised explosive devices. Patients had a median injury severity score (ISS) of 38 (IQR 30–45) and time from injury to first infecting K. pneumoniae isolate was 15 days (IQR 8–31). The median hospital stay was 49 days (IQR 28–70) and four patients died. All patients had received antibiotics prior to diagnosis. Twenty-three (46%) patients had initial isolates classified as MDR. There was no difference in age, ISS, or time from injury to first isolation among those who did and did not have initial MDR isolates. Sixteen patients had 64 serial isolates, of which 24 were wound, 20 respiratory, 14 blood and six urine. Three of these 16 patients died compared with 1 of 35 patients without serial isolates.Conclusion K. pneumoniae infections are common among combat casualties. Patients with K. pneumoniae infections were severely injured and almost half of initial infecting isolates were MDR, complicating treatment.Disclosures All authors: No reported disclosures.

Phenotypic Detection of Carbapenemase-Producing Organisms from Clinical Isolates

The rapid spread of multidrug-resistant Gram-negative organisms constitutes one of the greatest challenges to global health. While Gram-negative organisms have developed several mechanisms to avert the bactericidal effects of commonly prescribed antibiotic agents, the increasing prevalence of carbapenemase-producing organisms (CPO) is particularly concerning given the rapid spread of mobile genetic elements containing carbapenemase genes, the limited treatment options for infections caused by these organisms, and the high mortality rates associated with CPO infections. Understanding if an organism is carbapenemase producing and, if so, the class of carbapenemase(s) produced has treatment implications, as some agents preferentially have activity against specific carbapenemases. Furthermore, CPO disseminate between patients with greater ease than non-CP-carbapenem-resistant organisms and warrant more intensive infection control measures than would be employed in the absence of carbapenemase production. Phenotypic assays currently used in clinical practice to detect CPO consist of the following: (i) growth-based assays which measure carbapenem resistance based on organism growth in the presence of a carbapenem antibiotic (e.g., modified Hodge test and modified carbapenem inactivation method), (ii) hydrolysis methods which detect carbapenem degradation products (e.g., Carba NP test and matrix-assisted laser desorption-ionization time of flight mass spectrometry), and (iii) lateral flow immunoassays which detect carbapenemase enzymes through the use of specific antibodies. Although there is no single phenotypic test that meets all specifications of the ideal test, as we describe in this review, there are a number of tests that are user-friendly, affordable, accurate, and feasible for implementation in clinical microbiology laboratories of all sizes.

Increased detection of carbapenemase-producing Enterobacteriaceae on post-clean sampling of a burns unit's wet surfaces

Wet surface biofilms are a potential reservoir for multidrug-resistant Gram-negative organisms, including carbapenemase-producing Enterobacteriaceae (CPE). Recognition of environmental sources is important in reducing secondary patient transmission. We report the increased detection of blaIMP-4+ CPE in environmental samples from floor drains in burns unit shower rooms, when collected following cleaning as compared to pre-cleaning. We propose that disruption of biofilms during cleaning may account for the increased detection of multi-resistant organisms. The results highlight the role of the wet environment as an under-recognized potential source of CPE transmission. Environmental screening focusing on pre-cleaning samples alone will likely underestimate environmental contamination.

In-Hospital Surgery as a Risk Factor for Onset of AmpC-Producing Escherichia coli Blood Stream Infections

There has been a progressive rise in the incidence of blood stream infections (BSI) caused by multidrug-resistant Gram-negative organisms (MDR GN), which cause increased morbidity and mortality. For this reason, recent studies have focused on risk factors of acquisition of carbapenemase-producing Enterobacteriaceae and extended-spectrum beta-lactamase producers. However, there is limited data on risk factors for BSI caused by AmpC-producing Enterobacteriaceae (AmpC EC), especially in low prevalence settings such as Australia. This study was performed to identify risk factors for acquisition of AmpC E. coli, using a retrospective matched case control design over a 3-year period. Patients with BSI caused by AmpC E. coli were matched with controls (third generation cephalosporin susceptible E. coli) by age and site of infection (n = 21). There was no significant difference in age, sex, clinical outcome, time to onset of BSI, recent antibiotic use (last 3 months), comorbidities (type 2 diabetes mellitus, renal failure) intensive care unit admission, underlying hematological condition, immunosuppressant use, APACHE II score, or any recent urological procedures (within last 3 months) between the two groups. On univariate analysis, the AmpC E. coli group were more likely to have had a surgical procedure in hospital and lived in a residential aged care facility. On multivariate logistic regression analysis, a recent surgical procedure was associated with the onset of AmpC E. coli BSI (Odd’s Ratio (OR) 4.78, p = 0.034). We concluded that in a relatively low prevalence setting such as Australia, AmpC E. coli BSI is potentially associated with surgery performed in hospital due to previous antibiotic exposure and longer hospitalization.

Variability in contact precautions to control the nosocomial spread of multi-drug resistant organisms in the endemic setting: a multinational cross-sectional survey

BackgroundDefinitions and practices regarding use of contact precautions and isolation to prevent the spread of gram-positive and gram-negative multidrug-resistant organisms (MDRO) are not uniform.MethodsWe conducted an on-site survey during the European Congress on Clinical Microbiology and Infectious Diseases 2014 to assess specific details on contact precaution and implementation barriers.ResultsAttendants from 32 European (EU) and 24 non-EU countries participated (n = 213). In EU-respondents adherence to contact precautions and isolation was high for Methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae, and MDR A. baumannii (84.7, 85.7, and 80%, respectively) whereas only 68% of EU-respondents considered any contact precaution measures for extended-spectrum-beta-lactamase (ESBL) producing non-E. coli. Between 30 and 45% of all EU and non-EU respondents did not require health-care workers (HCW) to wear gowns and gloves at all times when entering the room of a patient in contact isolation. Between 10 and 20% of respondents did not consider any rooming specifications or isolation for gram-positive MDRO and up to 30% of respondents abstain from such interventions in gram-negative MDRO, especially non-E. coli ESBL. Understaffing and lack of sufficient isolation rooms were the most commonly encountered barriers amongst EU and non-EU respondents.ConclusionThe effectiveness of contact precautions and isolation is difficult to assess due to great variation in components of the specific measures and mixed levels of implementation. The lack of uniform positive effects of contact isolation to prevent transmission may be explained by the variability of interpretation of this term. Indications for contact isolation require a global definition and further sound studies.

Beware of broad-spectrum generalizations: ceftazidime-avibactam compared to meropenem for the treatment of gram-negative pneumonia.

Nosocomial pneumonia remains a serious challenge to modern healthcare and accounts for a substantial proportion of healthcare associated infections. Frequently, nosocomial pneumonia, and in particular ventilator-associated pneumonia, is caused by multi-drug resistant (MDR) Gram-negative organisms, leaving clinicians few effective therapeutic options.

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

BackgroundCeftazidime/avibactam is a newly approved β-lactam/β-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. MethodsA 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. ResultsTen 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. ConclusionsFor 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.

Effect of extended infusion of meropenem and nebulized amikacin on Gram-negative multidrug-resistant ventilator-associated pneumonia.

Background:Ventilator-associated pneumonia (VAP) due to multidrug-resistant organisms (MDROs) is associated with a significant mortality in the Intensive Care Unit (ICU). The aim of this study was to compare the efficacy and safety of extended infusion of meropenem and nebulized amikacin on VAP caused by Gram-negative MDRO versus intravenous (IV) meropenem and amikacin alone.Methodology:A randomized nonblinded controlled trial was performed on ninety patients with VAP. Patients were randomized into three equal groups: Group I received IV amikacin 20 mg/kg/24 h and meropenem 2 g over 30 min/8 h. Group II received the same as Group I in addition to nebulized amikacin 25 mg/kg/day every 8 h. Group III received IV amikacin 20 mg/kg/24 h, nebulized amikacin 25 mg/kg/day every 8 h, and meropenem 2 g diluted in 240 ml normal saline over 3 h/8 h. The primary outcome was the clinical outcome of VAP. Secondary outcomes were microbiological outcome, VAP-related mortality, duration of MV, ICU stay, and nephrotoxicity.Results:Group II and Group III compared to Group I showed higher incidence of clinical cure (53.33% in Group II and 66.67% in Group III vs. 26.67% in Group I, P = 0.007). Group II compared to Group I showed significant reduction in ventilator days (5.32 ± 1.86 vs. 7.3 ± 2.1 days, respectively, P < 0.001) and reduction in ICU days (11.87 ± 2.6 vs. 15.3 ± 3.1 days, respectively, P < 0.001). Group III compared to Group II showed significant reduction in ventilator days (4.22 ± 1.32 vs. 5.32 ± 1.86, respectively, P = 0.011) and highly significant reduction in ICU days (9.21 ± 1.17 vs. 11.87 ± 2.6, respectively, P < 0.001). All groups were comparable as regards nephrotoxicity or mortality.Conclusions:Adding nebulized amikacin to systemic antibiotics in patients with VAP caused by Gram-negative MDRO may offer efficacy benefits, and the use of extended infusions of meropenem could improve the clinical outcomes in critically ill populations.

Prevalence and Factors Associated With Multidrug-Resistant Gram-Negative Organisms in Patients With Spinal Cord Injury.

OBJECTIVE Infections caused by multidrug-resistant gram-negative organisms (MDRGNOs) have been increasing every year. The objective of this study was to describe the prevalence of MDRGNOs and factors associated with MDRGNOs in patients with spinal cord injury or disorder (SCI/D). DESIGN Retrospective cohort study. METHODS Department of Veterans Affairs (VA) electronic health record data from 142 VA facilities were evaluated for 19,642 patients with SCI/D. Multivariable cluster-adjusted models were fit to identify factors associated with MDRGNO. RESULTS Gram-negative (GN) cultures occurred in 44% of patients with SCI/D receiving care at VA facilities, and 11,527 (41.3%) GN cultures had an MDRGNO. The most frequent GN organisms (GNOs) were Escherichia coli (28.5%), Klebsiella pneumoniae (17.0%), and Pseudomonas aeruginosa (16.0%). Two-thirds of GN cultures were from the outpatient setting, where MDRGNO prevalence was 37.6%. Significant geographic variation in the prevalence of MDRGNOs was identified (South, 44.7%; Northeast, 44.3%; West, 36.8%; Midwest, 34.4%). Other factors associated with an MDRGNO were older age, injury characteristics, comorbidities, specimen type, healthcare setting, and healthcare exposure. Black (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.39-1.78) and Hispanic race (OR, 1.58; 95% CI, 1.28-1.95), polymicrobial culture (OR, 2.67; 95% CI, 2.46-2.90), and antibiotic use in the previous 90 days (OR, 1.62; 95% CI, 1.50-1.76) were also associated with having an MDRGNO. CONCLUSIONS MDRGNOs were common in community and healthcare settings among veterans with SCI/D, with significant geographic variation. Health care and antibiotic exposures were significant factors associated with MDRGNOs. Priority should be given to controlling the spread of MDRGNOs in this special population, including a focus on judicious use of antibiotics. Infect Control Hosp Epidemiol 2017;38:1464-1471.

Prevalence of Clostridium difficile and Multidrug Resistant Gram-negative Rods in the Soil from Southeastern Wisconsin

BackgroundPreliminary data suggests that community-onset Clostridium difficile might be more common in rural areas. Thus, farms—specifically livestock farms—might be a major reservoir of C. difficile. Similarly, antibiotic exposures might predispose farm animals for colonization with multidrug resistant Gram-negative organisms. The aim of this study was to determine the prevalence of C. difficile and multidrug resistant gram-negative rods in the soil of Southeastern Wisconsin farms.MethodsFrom July to September of 2016, soil samples were collected from farms with livestock animals. Soil samples were collected using gloves and sample containers. Soil samples were collected from farms specifically in or near Washington, Waukesha, and Milwaukee counties which are within the proximity of Milwaukee Metro area. Soil samples were cultured for C. difficile and Gram-negative rods on selective plates and by broth enrichment.ResultsA total of 20 farms participated in this study with a total of 40 soil samples. Out of the 40 soil samples, 20 were from an area where animals roam or where manure was used and the remaining 20 were from an area where animals are prohibited or where there was no manure. Out of the 20 soil samples where animals roam, 10 (50%), tested positive for C. difficile. Out of 20 soil samples where animals are prohibited, 13 samples (65%) tested positive for C. difficile. 2 of the 23 C. difficile isolates recovered were toxigenic. Eight (40%) of the 20 soil samples where animals roam tested positive for fluoroquinolone-resistant bacteria (FQR). While 5 (25%) of the 20 soil samples where animals are prohibited, tested positive for FQR bacteria. An Acinetobacter calcoaceticus was found to exhibit carbapenem-resistance.ConclusionWe found soil colonization with C. difficile and FQR in 65% and 25%, respectively, where animals are prohibited. Where animals roam we found C. difficile and FQR 50% and 40%, respectively. Our study suggests that farms may be a significant community source for C. difficile and fluoroquinolone resistant organisms. Additional testing should be done to examine factors that might be increasing antibiotic resistance in farms (e.g., antibiotic exposure).Disclosures All authors: No reported disclosures.

Polymyxin Resistance in Gram-negative Pathogens.

The polymyxins are one of the last line antimicrobial classes to retain activity against multidrug-resistant Gram-negative bacilli. However, with the increased use of polymyxins in recent years, reports of resistance have also been increasing. We aimed to describe the mechanisms and occurrence of polymyxin resistance in Gram-negative organisms and propose strategies to overcome resistance. The most common mechanism of acquired resistance to the polymyxins is via modification of the bacterial outer membrane lipopolysaccharide. Global epidemiological surveillance studies have reported the occurrence of polymyxin resistance to be most common in Enterobacteriaceae, specifically Enterobacter species and Acinetobacter baumannii. Prevalence of polymyxin-resistant Gram-negative organisms varies significantly by geographical location. Emergence of polymyxin resistance is of great concern, given the limited number of agents available to treat infections caused by multidrug-resistant Gram-negative organisms. Strategies to mitigate the development of polymyxin resistance include dose optimization and using polymyxin agents in combination with other highly active antimicrobial agents.

Acquisition of Multidrug-Resistant Gram-Negative Organisms During Travel.

The rate of multidrug resistance has continued to increase worldwide, presenting clinicians with further challenges related to patient care. In this article, we review information related to the acquisition of multidrug-resistant (MDR) Gram-negative organisms among travelers, including deployed personnel, as well as the potential impact on wound microbiology and travelers' diarrhea. Travel to Asia, experiencing travelers' diarrhea, and use of antibiotics, whereas abroad have been associated with an increased risk of acquiring MDR Enterobacteriaceae colonization. Acquisition of new pathogens (MDR and non-MDR) through travel may result in microbiome changes (both gastrointestinal and nongastrointestinal), which may lead to alterations in the gastrointestinal flora and antimicrobial resistance. Although the long-term impact of MDR Enterobacteriaceae is unknown, host colonization changes may occur, which could lead to infectious outcomes. In particular, a well-recognized complication is urinary tract infections (UTIs), whereas MDR wound infections, pneumonia, and travelers' diarrhea are also potential outcomes relevant to military health.

Risk factors for multidrug-resistant Gram-negative infection in burn patients.

Infection with multidrug-resistant (MDR) Gram-negative organisms leads to poorer outcomes in the critically ill burn patient. The aim of this study was to identify the risk factors for MDR Gram-negative pathogen infection in critically ill burn patients admitted to a major tertiary referral intensive care unit (ICU) in Australia. A retrospective case-control study of all adult burn patients admitted over a 7-year period was conducted. Twenty-one cases that cultured an MDR Gram-negative organism were matched with 21 controls of similar age, gender, burn size and ICU stay. Multivariable conditional logistic regression was used to individually assess risk factors after adjusting for Acute Burn Severity Index. Adjusted odds ratios (ORs) were reported. P-values < 0.25 were considered as potentially important risk factors. Factors increasing the risk of MDR Gram-negative infection included superficial partial thickness burn size (OR: 1.08; 95% confidence interval (CI): 1.01-1.16; P-value: 0.034), prior meropenem exposure (OR: 10.39; 95% CI: 0.96-112.00; P-value: 0.054), Gram-negative colonization on admission (OR: 9.23; 95% CI: 0.65-130.15; P-value: 0.10) and escharotomy (OR: 2.66; 95% CI: 0.52-13.65; P-value: 0.24). For cases, mean age was 41 (SD: 13) years, mean total body surface area burned was 47% (SD: 18) and mean days in ICU until MDR specimen collection was 17 (SD: 10) days. Prior meropenem exposure, Gram-negative colonization on admission, escharotomy and superficial partial thickness burn size may be potentially important factors for increasing the risk of MDR Gram-negative infection in the critically ill burn patient.

The role of Enterococcus spp. and multidrug-resistant bacteria causing pyogenic liver abscesses

BackgroundPyogenic liver abscesses (PLA) remain a significant clinical problem. Unfortunately, little is known about current bacterial susceptibility profiles and the incidence of multidrug resistant organisms (MDROs) causing PLA in Western countries. Yet, this crucial information is pivotal to guide empirical antibiotic therapy. Aim of this study was to provide detailed characteristics of PLA with a special focus on underlying bacterial pathogens and their susceptibility to antibiotics.MethodsA retrospective study of patients diagnosed with PLA from 2009 to 2015 in a large tertiary reference center in Germany was performed in order to characterize PLA and antimicrobial susceptibility profiles of causative bacterial species.ResultsOverall, 86 patients were included. The most common causes of PLA were bile duct stenosis/obstruction (31.4%) and leakage of biliary anastomosis (15.1%). Frequent predisposing diseases were malignancies (34.9%), diabetes (24.4%) and the presence of liver cirrhosis (16.3%). Of note, Enterococcus spp. were the most frequently cultured bacterial isolates (28.9%), and in 1/3 of cases vancomycin resistance was observed. In addition, a relevant frequency of gram-negative MDROs was identified. In particular, an alarming 10% and 20% of gram-negative bacteria were resistant to carbapenems and tigecycline, respectively. Of note, MDRO status did not predict ICU stay or survival in multivariate regression analysis. The mortality rate in our series was 16.3%.ConclusionOur study demonstrates an as yet underreported role of Enterococcus spp., often associated with vancomycin resistance, as well as of gram-negative MDROs causing PLA.

Long-lasting outbreak due to CTX-M-15-producing Klebsiella pneumoniae ST336 in a rehabilitation ward: report and literature review

Whereas Klebsiella species are the most frequently occurring agents in nosocomial outbreaks due to multidrug-resistant Gram-negative organisms, very few outbreaks have been reported from rehabilitation wards. To describe a long-lasting outbreak due to extended-spectrum β-lactamase-producing (ESBL) Klebsiella pneumoniae in a rehabilitation ward. ESBL K. pneumoniae from all in- and outpatients whose specimens were tested at a tertiary care university hospital between 2007 and 2012 were typed by pulsed-field gel electrophoresis and selected isolates were submitted to multi-locus sequence typing and ESBL genotyping. Outbreak characteristics and infection control interventions were summarized. The literature was searched for K. pneumoniae-related outbreaks in rehabilitation wards. ESBL K. pneumoniae was detected in 69 out of 2478 K. pneumoniae-positive patients (2.8%) during the study period. Eight related outbreak clones from 35 patients, 25 of whom were in the rehabilitation ward, produced CTX-M-15 and belonged to ST336. The outbreak lasted for more than three years and was controlled by sequentially increasing measures culminating in review of all patient-related care, compulsory educational meetings for personnel, profession-specific guidelines and educational flyers for patients. Half of ESBL K. pneumoniae-positive patients identified over six years at a tertiary care university hospital harboured related clones, and more than a third were hospitalized in a rehabilitation ward. Rehabilitation wards pose particular challenges for infection control because of patient dependency and an environment that encourages socializing. They are, however, rarely involved in K. pneumoniae-related outbreaks.

Elevated prevalence of multidrug-resistant gram-negative organisms in HIV positive men

BackgroundRoutes of transmission of multidrug-resistant gram-negative organisms (MDRGN) are not completely understood. Since sexual transmission of MDRGN might represent a potential mode that has not been noticed so far, this study evaluated transmission of MDRGN in HIV positive men.MethodsBetween November 2014 and March 2016, we retrospectively investigated the MDRGN prevalence in rectal swabs of n = 109 males tested positive for HIV (HP). These findings were compared to the MDRGN prevalence in n = 109 rectal swabs in age-matched males tested negative for HIV (HN) within the same period. According to the infection control protocol of University Hospital Frankfurt, Germany (UHF), patients admitted to intensive/intermediate care units have to be screened for MDRGN on day of admittance. Patients without HIV testing or MDRGN screening were excluded.ResultsMDRGN prevalence in rectal swabs was significantly higher (p = 0.002) in male HP (23.9%; 95% confidence interval 16.2–32.9%) than in age-matched male HN (8.3%; 3.8–15.1%). In total, 35 MDRGN species were detected. The most frequent MDRGN species was Escherichia coli with resistance due to ESBL expression and additional resistance to fluoroquinolones with n = 25/35 (71.4%; 53.7–85.4%). Thereof, n = 19/26 (73.1%; 52.2–88.4%) were detected in HP and n = 6/9 (66.7%; 29.9–92.5%) in HN, respectively.ConclusionsPrevalence of MDRGN is significantly higher in male HIV positive than in male HIV negative individuals. This might indicate sexual transmission of MDRGN within the male HIV positive population. As treatment options in case of MRGN infections are limited, prevention of MDRGN transmission is strongly emphasized.

Factors associated with carriage of carbapenem-non-susceptible Enterobacteriaceaein North-Eastern France and outcomes of infected patients.

Carbapenems are frequently used as a last resort to treat infections caused by multidrug-resistant Gram-negative organisms, thus carbapenem-non-susceptible Enterobacteriaceae (CNSE) is an emerging health threat. To assess risk factors and outcomes of CNSE carriage. We conducted a matched case-control study in six hospitals in North-Eastern France. The controls were patients harbouring carbapenem-susceptible Enterobacteriaceae. Fifty-five cases and 110 controls were included. Most of the CNSE isolates were Enterobacter cloacae and Klebsiella pneumoniae . Carbapenemase production was observed in 40% of isolates and they produced OXA-48 only. CNSE carriage was significantly associated with recent antibiotic use ( P = 0.014), particularly carbapenems ( P = 0.03) and fluoroquinolones ( P = 0.016). A multivariate analysis using conditional logistic regression showed that the presence of concomitant infection(s) (OR: 9.83; 95% CI 3.04-21.39, P = 0.0031), nosocomial infections (OR: 7.84; 95% CI 2.00-12.54, P = 0.0063) and a high age (OR: 1.07; 95% CI 1.01-1.06, P = 0.038) were independently associated with CNSE carriage. Moreover, patients infected with CNSE had worse outcomes: fewer resolved infections at 1 month ( P = 0.02), and they had a higher mortality rate ( P = 0.0004) and longer hospital stays ( P = 0.02). We identified three independent risk factors for CNSE carriage as well as worse outcomes in infected patients in North-Eastern France. This highlights the importance of early detection of CNSE and the need for antimicrobial therapy re-evaluation after bacteriological analysis has been performed.

Outcomes of Rapid Identification of Multi-Drug Resistant Gram-Negative Organisms Causing Bacteremia in Combination with Antimicrobial Stewardship in a Community Health System.

BackgroundRapid initiation of effective antibiotic therapy has been strongly associated with a decrease in mortality in gram-negative (GN) bacteremia. In an effort to improve time to effective antibiotic therapy in the treatment of multi-drug resistant (MDR) GN bacteremia, we implemented Verigene GN Blood Culture (BC-GN) assay, which can rapidly identify GN bacteria at the genus/species level and specific resistance markers from blood cultures within 2 hours of positivity.MethodsThe objective of this multi-center, pre-post quasi-experimental study was to assess outcomes of Verigene BC-GN in combination with antibiotic stewardship in treatment of MDR GN bacteremia. A retrospective chart review was performed one year prior and four months post-implementation of Verigene BC-GN. Patients > 18 years old with MDR GN bacteremia identified by Verigene BC-GN within 5 days of admission were included. The primary endpoint was time to effective antibiotic therapy for MDR GN bacteremia. Secondary outcomes included overall and ICU length of stay (LOS) and 30-day mortality. Education regarding interpretation of resistance markers and selection of optimal antibiotic therapy was provided to pharmacists and physicians prior to implementation.ResultsA total of 110 patients were included, 86 in the pre-intervention group and 24 in the post-intervention group. Mean time to effective antibiotic therapy decreased significantly from 47.6 ± 23.1 vs. 18.8 ± 9.1 hours, respectively (P < 0.0001). Median overall LOS was 6.0 vs 5.5 days (P = 0.88), ICU LOS was 3.0 vs 4.0 days (P = 0.57), and 30-day mortality was 4.7% vs 4.2% (P = 1) pre and post-implementation, respectively.ConclusionVerigene BC-GN, in combination with antibiotic stewardship, successfully improved time to effective antibiotic therapy among MDR GN organisms causing bacteremia.Disclosures All authors: No reported disclosures.