Enterobacteriaceae Bloodstream Infections Research Articles

Clinical Risk Score for Prediction of Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Bloodstream Isolates.

OBJECTIVE To develop a risk score to predict probability of bloodstream infections (BSIs) due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE). DESIGN Retrospective case-control study. SETTING Two large community hospitals. PATIENTS Hospitalized adults with Enterobacteriaceae BSI between January 1, 2010, and June 30, 2015. METHODS Multivariate logistic regression was used to identify independent risk factors for ESBLE BSI. Point allocation in extended-spectrum β-lactamase prediction score (ESBL-PS) was based on regression coefficients. RESULTS Among 910 patients with Enterobacteriaceae BSI, 42 (4.6%) had ESBLE bloodstream isolates. Most ESBLE BSIs were community onset (33 of 42; 79%), and 25 (60%) were due to Escherichia coli. Independent risk factors for ESBLE BSI and point allocation in ESBL-PS included outpatient procedures within 1 month (adjusted odds ratio [aOR], 8.7; 95% confidence interval [CI], 3.1-22.9; 1 point), prior infections or colonization with ESBLE within 12 months (aOR, 26.8; 95% CI, 7.0-108.2; 4 points), and number of prior courses of β-lactams and/or fluoroquinolones used within 3 months of BSI: 1 course (aOR, 6.3; 95% CI, 2.7-14.7; 1 point), ≥2 courses (aOR, 22.0; 95% CI, 8.6-57.1; 3 points). The area under the receiver operating characteristic curve for the ESBL-PS model was 0.86. Patients with ESBL-PSs of 0, 1, 3, and 4 had estimated probabilities of ESBLE BSI of 0.7%, 5%, 24%, and 44%, respectively. Using ESBL-PS ≥3 to indicate high risk provided a negative predictive value of 97%. CONCLUSIONS ESBL-PS estimated patient-specific risk of ESBLE BSI with high discrimination. Incorporation of ESBL-PS with acute severity of illness may improve adequacy of empirical antimicrobial therapy and reduce carbapenem utilization. Infect Control Hosp Epidemiol 2017;38:266-272.

Differential effect of prior β-lactams and fluoroquinolones on risk of bloodstream infections secondary to Pseudomonas aeruginosa

ObjectiveThis retrospective case–control study examines risk factors for bloodstream infections (BSI) due to Pseudomonas aeruginosa (PSA). MethodsHospitalized adults with Gram-negative BSI at Palmetto Health from 2010 to 2015 were identified. Multivariate logistic regression was used to examine PSA BSI risk factors. ResultsSeventy and 910 patients with PSA and Enterobacteriaceae BSI, respectively, were included. Prior use of β-lactams (adjusted odds ratio [aOR] 3.9, 95% confidence intervals [CI]: 2.3–6.9), but not fluoroquinolones (aOR 1.0, 95% CI: 0.4–2.2), was a risk factor for PSA BSI. Immune compromised status (aOR 3.7, 95% CI: 2.0–6.7), respiratory source (aOR 4.4, 95% CI: 2.1–8.9), and prolonged hospitalization (aOR 1.9, 95% CI: 1.1–3.5), were predictors of PSA BSI. ConclusionsDetermination of class of previously used antibiotics among other clinical variables helps identify patients at risk of PSA BSI and offers opportunities to optimize empirical antimicrobial therapy.

Association between chronic hemodialysis and bloodstream infections caused by chromosomally mediated AmpC-producing Enterobacteriaceae.

The combination of inherent antimicrobial resistance and high mortality after bloodstream infections (BSIs) caused by chromosomally mediated AmpC-producing Enterobacteriaceae (CAE) emphasizes the importance of identifying patients at risk of BSI because of these bacteria. This retrospective case-control study examines chronic hemodialysis among other risk factors for BSI caused by CAE. Hospitalized adults with Enterobacteriaceae BSI from January 1, 2010-June 30, 2014, at 2 large community hospitals in the Southeastern United States were identified. Multivariate logistic regression was used to examine risk factors for CAE BSI. Among 831 Enterobacteriaceae bloodstream isolates, 106 (13%) met the phenotypic definition of CAE. Enterobacter spp accounted for 47% (50/106) of CAE BSIs. Chronic hemodialysis was an independent risk factor for CAE BSI (adjusted odds ratio [aOR], 2.34; 95% confidence interval [CI], 1.21-4.44). Other predictors of CAE BSI included nosocomial acquisition (aOR, 1.72; 95% CI, 1.02-2.87) and exposure to β-lactam antibiotics within the last 30 days (aOR, 2.39; 95% CI, 1.37-4.14). To our knowledge, this is the first study to demonstrate an increased risk of CAE BSI in patients with end-stage renal disease undergoing chronic hemodialysis. This highlights the importance of effective infection prevention and antimicrobial stewardship interventions in hemodialysis clinics. Further studies to examine the impact of antibiotics on intestinal microbiota and rates of CAE colonization in this patient population are warranted.

Empirical therapy of bloodstream infections caused by extended-spectrum β-lactamase-producing Enterobacteriaceae

To compare the clinical outcomes and costs associated with carbapenems and β-lactam/β-lactamase inhibitor combinations (BLBLIs) for the empirical treatment of patients with extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae bloodstream infections (BSIs). The medical records of individuals diagnosed with ESBL-producing Escherichia coli and Klebsiella pneumoniae BSIs between January 2014 and June 2015 at Changhai Hospital were reviewed. Patients were divided into two groups based on the empirical therapy (carbapenems group and BLBLIs group). Propensity score matching in a 1∶1 ratio was used to match the patients from two groups. Clinical outcomes and costs were compared before and after matching. One hundred and fifty-eight patients were analyzed, 93 in the carbapenems group and 65 in the BLBLIs group. Before matching, the two groups were significantly different in department distribution, tumor rate, deep vein catheter rate, urinary catheter rate, nasogastric tube rate, and mechanical ventilation rate (all P<0.05), and the carbapenems group had longer total length of stay (LOS) and post-BSI LOS (26.0 vs 18.0 d, P=0.029 and 12.0 vs 10.0 d, P=0.044) , higher hospital cost and daily hospital cost (84 120 vs 39 000 ￥, P<0.001 and 3 451 vs 2 574 ￥, P=0.002). After matching, the two groups had no significant differences in covariates such as sex, age, department distribution, pathogens, comorbidities, invasive interventions, LOS before BSI, multiple admissions, surgical rate during hospitalization and delayed antimicrobial therapy (all P>0.05). Finally, there were no differences between two groups in mortality, post-BSI LOS, total LOS, hospital cost and antimicrobial cost (all P>0.05). BLBLIs may provide a reasonable carbapenem-sparing option for the empirical treatment of ESBL producers.

Characterization and Clinical Impact of Bloodstream Infection Caused by Carbapenemase-Producing Enterobacteriaceae in Seven Latin American Countries.

IntroductionInfections caused by carbapenem-resistant Enterobacteriaceae are a public health problem associated with higher mortality rates, longer hospitalization and increased healthcare costs. We carried out a study to describe the characteristics of patients with carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE bloodstream infection (BSI) from Latin American hospitals and to determine the clinical impact in terms of mortality and antibiotic therapy.MethodsBetween July 2013 and November 2014, we conducted a multicenter observational study in 11 hospitals from 7 Latin American countries (Argentina, Colombia, Ecuador, Guatemala, Mexico, Peru, Venezuela). Patients with BSI caused by Enterobacteriaceae were included and classified either as CPE or non-CPE based on detection of blaKPC, blaVIM, blaIMP, blaNDM and blaOXA-48 by polymerase chain reaction.Enrolled subjects were followed until discharge or death. Demographic, microbiological and clinical characteristics were collected from medical records. Both descriptive and inferential statistics were used to analyze the information.ResultsA total of 255 patients with Enterobacteriaceae BSI were included; CPE were identified in 53 of them. In vitro non-susceptibility to all screened antibiotics was higher in the patients with CPE BSI, remaining colistin, tigecycline and amikacin as the most active drugs. Combination therapy was significantly more frequent in the CPE BSI group (p < 0.001). The most common regimen was carbapenem + colistin or polymyxin B. The overall mortality was 37% (94/255). Overall and attributable mortality were significantly higher in patients with CPE BSI (p < 0.001); however, we found that patients with CPE BSI who received combination therapy and those who received monotherapy had similar mortality. After multivariate adjustment, CPE BSI (adjusted odds ratio [aOR] 4; 95% confidence interval [CI] 1.7–9.5; p = 0.002) and critical illness (aOR 6.5; 95% CI 3.1–13.7; p < 0.001) were independently associated with in-hospital mortality.ConclusionsThis study provides valuable data on the clinical characteristics and mortality risk factors in patients with CPE BSI. We determined that CPE infection is an independent mortality predictor and thus Latin American hospitals should perform campaigns on prevention and control of CPE BSI.

Epidemiology and Burden of Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae in a Pediatric Hospital in Senegal.

ContextSevere bacterial infections are not considered as a leading cause of death in young children in sub-Saharan Africa. The worldwide emergence of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) could change the paradigm, especially in neonates who are at high risk of developing healthcare-associated infections.ObjectiveTo evaluate the epidemiology and the burden of ESBL-E bloodstream infections (BSI).MethodsA case-case-control study was conducted in patients admitted in a pediatric hospital during two consecutive years. Cases were patients with Enterobacteriaceae BSI and included ESBL-positive (cases 1) and ESBL-negative BSI (cases 2). Controls were patients with no BSI. Multivariate analysis using a stepwise logistic regression was performed to identify risk factors for ESBL acquisition and for fatal outcomes. A multistate model was used to estimate the excess length of hospital stay (LOS) attributable to ESBL production while accounting for time of infection. Cox proportional hazards models were performed to assess the independent effect of ESBL-positive and negative BSI on LOS.ResultsThe incidence rate of ESBL-E BSI was of 1.52 cases/1000 patient-days (95% CI: 1.2–5.6 cases per 1000 patient-days). Multivariate analysis showed that independent risk factors for ESBL-BSI acquisition were related to underlying comorbidities (sickle cell disease OR = 3.1 (95%CI: 2.3–4.9), malnutrition OR = 2.0 (95%CI: 1.7–2.6)) and invasive procedures (mechanical ventilation OR = 3.5 (95%CI: 2.7–5.3)). Neonates were also identified to be at risk for ESBL-E BSI. Inadequate initial antibiotic therapy was more frequent in ESBL-positive BSI than ESBL-negative BSI (94.2% versus 5.7%, p<0.0001). ESBL-positive BSI was associated with higher case-fatality rate than ESBL-negative BSI (54.8% versus 15.4%, p<0.001). Multistate modelling indicated an excess LOS attributable to ESBL production of 4.3 days. The adjusted end-of-LOS hazard ratio for ESBL-positive BSI was 0.07 (95%CI, 0.04–0.12).ConclusionControl of ESBL-E spread is an emergency in pediatric populations and could be achieved with simple cost-effective measures such as hand hygiene, proper management of excreta and better stewardship of antibiotic use, especially for empirical therapy.

Global Antimicrobial Stewardship: Challenges and Successes from Frontline Stewards.

Global Antimicrobial Stewardship: Challenges and Successes from Frontline Stewards.

Antibiotic Prophylaxis Revisited: The Impact of Fluoroquinolones on Epidemiology and on the Emergence of Resistant Strains in Acute Leukemia Patients. Results of a Prospective Study By the Rete Ematologia Lombarda (REL)

▪Introduction. Multiresistant (multiR) bacteria are emerging pathogens in hematologic cancer patients (pts) and may negatively impact on the outcome of bloodstream infections (BSI). The antibiotic pressure, including fluoroquinolones (Fq) prophylaxis, may be one of the factors responsible for this phenomenon. In order to better define the very recent epidemiology and outcome of BSI in a real-life setting, we planned a prospective study collecting all consecutive febrile/infectious episodes occurring in acute leukemia (AL) pts admitted to 9 hematological institutions participating to REL, representing about 75% of the entire AL population treated in Lombardy.Patients and Methods. From Dec-2012 to Jul-2014, all febrile/infectious episodes were recorded. The following data concerning BSI were analysed: age, gender, type and phase of leukemia, neutropenia, Fq prophylaxis, presence of central venous catheter (CVC), concomitant pulmonary infiltrates, antibiotic resistance.Results. In 218 AL pts (M/F 131/87; median age 54y, range 17-80; AML/ALL 181/37), 314 BSI were diagnosed. In 180 (57.3%) BSI occurred in pts on Fq prophylaxis. In 71 (22.6%) pneumonia was also present. Gram-positive cocci (GPC) were isolated in 145/314 BSI (46.2%); Gram-negative rods (GNR) in 117 (37.3%), polymicrobial (PMB) aetiology in 48 (15.3%) and fungi (F) in 4 (1.3%). Coagulase-negative staphylococci (CoNS) were the most frequent GPC (105/314, 33.4%); S. aureus, S. viridans and enterococci were observed in 7 (2.2%), 17 (5.4%) and 37 (11.8%) cases, respectively. Methicillin-resistant strains accounted for 75.9% of all staphylococci and vancomycin-resistant strains for 2.7% of enterococci. CVC-related BSI, which accounted for 31.4% of BSI occurring in pts with CVC, was independently correlated with GPC aetiology (OR 1.9, CI 1.1-3.1, p=0.01). Considering GNR, Enterobacteriaceae were isolated in 113/314 BSI (36%) and P. aeruginosa in 31 (9.9%). GNR occurred more frequently during consolidation cycles (45.8% vs 31.1%) and in pts not on Fq prophylaxis (44.2% vs 32.2%). Both conditions were independent risk factors at multivariate analysis (p=0.002 and p=0.02, respectively). Frequency of Enterobacteriaceae BSI was also higher during consolidation cycles in comparison with other AL phases (48.1% vs 27.3%, p=0.0005), but Fq prophylaxis was no longer a protective factor (35% vs, 37.3%). Fq resistance was observed in 63/113 (55.7%) of Enterobacteriaceae; in 84.1% of cases were detected during Fq prophylaxis. ESBL+ strains, which accounted for 24.8% of Enterobacteriaceae, were also associated with Fq prophylaxis (OR 2.8, CI 1.1-7.1, p=0.02) at multivariate analysis. Carbapenemase producing (CP) strains occurred in 8.8% of Enterobacteriaceae. Among P. aeruginosa strains, 19.4% were multiR. Thirty-day mortality was 7.6% (24/314); it was lower for GPC (5.5%) in comparison with GNR (9.4%) and PMB BSI (11.6 %). CP Enterobacteriaceae or multiR P. aeruginosa BSI (30d mortality: 33.3%; OR 21.3, CI 4.4-102.4, p=0.0001) but not ESBL+ strains were independent predictors of death. Furthermore, having relapsed/resistant AL (18.2%; OR 9, CI 2.7-30.7, p=0.0004), and the presence of concomitant pulmonary infiltrates (26.8%; OR 15, CI 4.8-46.8, p<0.001) significantly correlated with the risk of death at multivariate analysis.Conclusions. The proportion of multiresistant GNR is becoming a major problem in our real-life prospective study. Fq prophylaxis reduced the proportion of GNR BSI as a whole, but not those incurred by Enterobacteriaceae, mainly observed during consolidation phases. Moreover, Fq exposure was associated with ESBL+ aetiology, which also occurred during consolidation cycles. While ESBL+ did not impact on survival, both multiR- and CP-bacteria correlated with a higher risk of death. Interestingly, also a concomitant diagnosis of pneumonia during BSI was a strong predictor of a poorer outcome. The usefulness of Fq prophylaxis has to be reanalysed in this new epidemiologic scenario. DisclosuresNo relevant conflicts of interest to declare.

Support for higher ciprofloxacin AUC24/MIC targets in treating Enterobacteriaceae bloodstream infection

Given concerns regarding optimal therapy for serious Gram-negative infections, the goal was to characterize the pharmacodynamics of ciprofloxacin in the context of treating bloodstream infection. Data were collected from the medical records of 178 clinical cases. Blood isolates were retrieved and ciprofloxacin MICs were measured. Forty-two cases in which ciprofloxacin was initiated within 24 h of the positive blood culture were used in the pharmacodynamic analysis. Significant factors with regard to treatment failure were low ciprofloxacin AUC(24)/MIC (P < 0.0001), high MIC (P = 0.001), male sex (P = 0.002) and low AUC(24) (P = 0.01). AUC(24)/MIC (P = 0.012) and MIC (P = 0.019) were significant variables in multivariate analyses; however, only the former remained significant (P = 0.038) after excluding two cases with ciprofloxacin-resistant isolates. An AUC(24)/MIC breakpoint of 250 was most significant, with cure rates of 91.4% (32/35) and 28.6% (2/7) in patients with values above and below this threshold, respectively (P = 0.001). The risk of ciprofloxacin treatment failure was 27.8 times (95% confidence interval, 2.1-333) greater in those not achieving an AUC(24)/MIC >or=250 (P = 0.011). Monte Carlo simulation of 5000 study subjects predicted that 0.88 of the population would achieve an AUC(24)/MIC >or=250 with standard-dose ciprofloxacin (400 mg intravenously every 12 h). This study confirms the pharmacodynamic parameters of ciprofloxacin that are important for optimizing the treatment of serious infections, particularly the benefits of achieving an AUC(24)/MIC >or=250, rather than the conventional target of >or=125. It also shows the relevance of dose selection in optimizing target attainment, with important differences among pathogens, even those with MICs within the susceptible range.

Bloodstream infections caused by qnr-positive Enterobacteriaceae: clinical and microbiologic characteristics and outcomes

The clinical significance of plasmid-mediated quinolone resistance determinant qnr has not been well characterized. We investigated the clinical and microbiologic characteristics and outcomes of bloodstream infections (BSIs) caused by qnr-positive Enterobacteriaceae. We prospectively collected 351 nonduplicate consecutive blood isolates of Enterobacter spp. and Klebsiella pneumoniae. qnr genes were detected by polymerase chain reaction and confirmed by sequencing. The medical records of patients were retrospectively reviewed. qnr genes were detected in a total of 26 isolates. A comparison of these 26 qnr-positive and 297 qnr-negative Enterobacteriaceae BSIs in adult patients showed that the population characteristics and clinical features of BSIs were similar between the qnr-positive and qnr-negative groups. However, patients with hematologic malignancies, solid organ transplant recipients, and BSIs caused by strains with multiple antimicrobial resistance, including extended-spectrum β-lactamase (ESBL) resistance, were more common in the qnr-positive group. Previous antibiotic therapy and prior use of trimethoprim–sulfamethoxazole or aminoglycosides were significantly associated with BSIs caused by qnr-positive strains. In the multivariate analysis, prior use of trimethoprim–sulfamethoxazole (odds ratio [OR], 5.55; 95% confidence interval [CI], 1.47–20.94) and having an underlying disease other than solid tumor (OR, 4.06; 95% CI, 15.07) were independently associated with qnr-positive Enterobacteriaceae BSIs. There was no significant difference in 30-day mortality rates between the qnr-positive and qnr-negative groups (15.4% [4/26] versus 13.8% [41/297], P = 0.77). Although qnr determinants were significantly associated with multiple antimicrobial resistance including ESBL resistance, they did not affect clinical outcomes of BSIs.

P6 Benefit of achieving higher AUC/MIC targets with ciprofloxacin when treating Enterobacteriaceae bloodstream infections

P6 Benefit of achieving higher AUC/MIC targets with ciprofloxacin when treating Enterobacteriaceae bloodstream infections

Effects on spectrum and susceptibility patterns of isolates causing bloodstream infection by restriction of fluoroquinolone prophylaxis in a hematology–oncology unit

The emergence of fluoroquinolone-resistant gram-negative organisms has been demonstrated in patients given fluoroquinolone prophylaxis. To prevent increases in resistant bacteria, we restricted prophylactic use of fluoroquinolones. The spectrum and susceptibility patterns of isolates causing bloodstream infection (BSI) were assessed in patients receiving chemotherapy during periods of routine prophylaxis (period A: October 2001 to May 2003) and restricted prophylaxis (period B: June 2003 to January 2005). The total number of patients receiving chemotherapy was 442 during period A and 365 during period B. No significant differences were seen between periods with respect to patient characteristics. BSI was identified in 42 patients (44 episodes) during period A and 69 patients (74 episodes) during period B. Incidence of BSI increased significantly from 10.0% (44/442) during period A to 20.3% (74/365) during period B (P < 0.0001). Rate of Enterobacteriaceae BSI increased significantly, from 2.0% (9/442) during period A to 8.2% (30/365) during period B (P < 0.0001). For all BSI episodes, the proportion of BSI with gram-positive cocci decreased from 63.6% (28/44) during period A to 44.6% (33/74) during period B (P = 0.045), while the proportion of BSI with Enterobacteriaceae increased from 20.5% (9/44) to 40.5% (30/74) (P < 0.0001). The proportion of fluoroquinolone-resistant Enterobacteriaceae BSI for all Enterobacteriaceae BSI decreased from 75% (9/12) during period A to 17% (5/30) during period B (P = 0.0078). Restriction of fluoroquinolone prophylaxis affects the etiology of BSI and reduces the proportion of drug-resistant organisms.

Accuracy of the Vitek system for antimicrobial susceptibility testing Enterobacteriaceae bloodstream infection isolates: use of “direct” inoculation from Bactec 9240 blood culture bottles

A recent investigation indicates that rapid antimicrobial susceptibility tests (AST) can affect patient therapy leading to reductions in health-care costs for some patient populations. However, there is little information relative to the often performed direct inoculation of positive blood culture bottles into rapid AST systems. AST results of direct inoculated Vitek (bioMerieux Vitek, Hazelwood, MO, USA) GNS cards were compared to those inoclated per package insert recommendations and a reference broth microdilution test using 50 consecutive Enterobacteriaceae bloodstream infection isolates. Escherichia coli (44% of isolates), Klebsiella ssp. (30%), and six other members of this family were tested against 15 antimicrobial agents. The direct inoculation method produced only two false-susceptible (0.3%), seven false-resistant (0.9%; six different drugs), and 48 minor errors (6.4%). The GNS cards inoculated in the usual, recommended manner had no very major error, and 7.5% combined major and minor errors. If the results of the urinary infection-specific drugs (nitrofurantoin, trimethoprim/sulfamethoxazole; not appropriate for bacteremia therapy) and ampicillin/sulbactam were deleted, both Vitek inoculation methods yielded results well within acceptable limits (≤4.5% overall error). These results indicate that the direct inoculation method of Vitek GNS cards from Enterobacteriaceae bloodstream infections (detected by Bactec 9240, Becton-Dickinson, Cockeysville, MD, USA) performed as well as the NCCLS broth microdilution test. Thus, a procedural modification of this type could further accelerate rapid access to accurate AST data.