Yonit Wiener-Well

National Multicenter Study of Predictors and Outcomes of Bacteremia upon Hospital Admission Caused by Enterobacteriaceae Producing Extended-Spectrum β-Lactamases

ABSTRACT Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.

Duration of carriage of carbapenem-resistant Enterobacteriaceae following hospital discharge

BACKGROUND Hospitalized carriers of carbapenem-resistant Enterobacteriaceae (CRE) are cohorted under contact precautions, including in the days between rehospitalization and surveillance culture results. This study investigates duration of CRE carriage to define populations requiring precautions upon readmission. METHODS Patients with CRE-positive culture during 2009-2010 were followed up by rectal swab cultures taken retrospectively and prospectively for the study or as part of clinical follow-up. RESULTS One hundred thirty-seven patients met the inclusion criteria, with follow-up cultures obtained from 97. Mean time to CRE negativity was 387 days (95% confidence interval: 312-463). Seventy-eight percent of patients (64/82) had positive culture at 3 months, 65% (38/58) at 6 months, and 39% (12/30) at 1 year. Duration of carriage was affected by repeat hospitalization (P = .001) and clinical, as opposed to surveillance, culture (P = .002). CONCLUSION CRE carriers from a previous hospitalization have a lower probability of CRE carriage upon readmission if the index specimen was a surveillance culture and 1 year passed without further hospitalization. Multiple hospitalizations and CRE disease extend duration of carriage. This study better defines patients requiring cohorting and isolation, thus limiting spread of CRE and allowing for improved allocation of infection control measures.

Carriage rate of carbapenem-resistant Klebsiella pneumoniae in hospitalised patients during a national outbreak

During a national outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Israel, we conducted a point prevalence survey to determine the extent of asymptomatic carriage. Subsequently, a retrospective case-control study was done, comparing carriers of CRKP with non-carriers, in order to detect risk factors for carriage. Oral, perianal and rectal swabs were obtained from all hospitalised eligible and consenting patients. Selective media for carbapenem-resistant Gram-negative bacteria were used and pulsed-field gel electrophoresis (PFGE) helped to determine clonal source. Culture was obtained from 298 patients. Sixteen (5.4%) were carriers of CRKP, with a higher carriage rate in medical and surgical wards. Only 18% of carriers were treated with any carbapenem prior to the survey. Five of the 16 carriers had a positive clinical specimen for CRKP, hence a clinical infection versus asymptomatic carriage ratio of 1:3. The rectum was the most sensitive site sampled, detecting 15/16 carriers, and the overall sensitivity of the method was 94% with a negative predictive value of 99.6%. In a multivariate analysis of risk factors for CRKP carriage, three variables were significantly related to carriage state: diaper use, longer duration of hospital stay and vancomycin use. PFGE demonstrated that all 16 isolates were identical, confirming clonal origin. A point prevalence survey performed at a single medical centre during an outbreak of CRKP demonstrated a carriage rate of 5.4%. The clonal origin of these isolates suggests that strict adherence to isolation procedure may contain this outbreak.

Antibiotic Exposure as a Risk Factor for Fluconazole-Resistant Candida Bloodstream Infection

ABSTRACT Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole-resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the models predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.

Incidence and risk factors for surgical infection after total knee replacement

Surgical site infection (SSI) after total knee replacement (TKR) is a devastating complication. We performed a retrospective study of all consecutive TKRs performed during a 2-y period. Surgical site infection (SSI) was defined by standard criteria. All patients were examined 1 y following surgery. Of 180 patients undergoing TKR, 10 (5.6%) developed a superficial (3, 1.7%) or deep (7, 3.9%) SSI. Two independent risk factors for SSI were detected: left knees became infected more often (9/92, 9.8%) than right knees (1/88, 1.1%) (Relative Risk 6.7±95% CI 1.7–26.8); and 7/72 (9.7%) patients receiving a type-1 prosthesis developed infection versus 3/104 (3.1%) receiving a type-2 prosthesis (RR 4.7, 95% CI 1.18–18.4). Investigation of the operating room revealed 3 problems: there was significant traffic through the door on the left of the patient; a non-standard horizontal-flow air conditioner had been installed above that door; a tool-washing sink was in use on the other side of that door. Infection control guidelines were rehearsed: the sink was removed, the air conditioner was disconnected, and the door was locked. In a prospective survey performed 2 y later only 1/45 patients (2.2%) undergoing TKR developed a superficial SSI (p=0.5). Correction of independent risk factors for infection following TKR led to a decrease in SSI rate.

Coxsackievirus A6-related hand foot and mouth disease: Skin manifestations in a cluster of adult patients

BACKGROUND Hand foot and mouth disease (HFMD) is a common childhood manifestation of enterovirus (EV) infection. It predominantly affects young children, and has been mainly associated with coxsackievirus (CV) A16 and EV 71. OBJECTIVES We report an unusual cluster of adult patients with HFMD. STUDY DESIGN Throat swabs and vesicular fluid samples obtained from patients admitted to the emergency room (ER) with HFMD were tested for EV by reverse transcription (RT)-real time PCR, and further subjected to sequencing and phylogenetic analysis. RESULTS CVA6 was identified as the causative agent of HFMD in five epidemiologically-unrelated adult patients (28-37 years old) admitted to the ER between December 2012 and February 2013. Phylogenetic analysis mapped the CVA6 strains into one cluster. All patients manifested with fever and a severe vasculitis-like rash, followed by spontaneous recovery. CONCLUSIONS This cluster identifies CVA6 as an emerging cause of HFMD of unusual age distribution, seasonality, and clinical severity, underscoring the need for continued alertness and clinical-genotypic surveillance of EV HFMD.

Mortality due to blaKPC Klebsiella pneumoniae bacteraemia

OBJECTIVES To determine the mortality rate secondary to blaKPC Klebsiella pneumoniae (KPC/Kp) bacteraemia, compared with that from ESBL-producing K. pneumoniae (ESBL/Kp) bacteraemia, and to determine associated risk factors. METHODS This was a retrospective case-control study of all 68 KPC/Kp bacteraemia patients diagnosed since 2006, matched by year of isolation, gender and age, at a ratio of 1:2, to 136 ESBL/Kp bacteraemia patients. RESULTS There were no demographic differences between the two groups, but there were minor clinical differences. Fewer KPC/Kp study patients than ESBL/Kp control patients had a systolic blood pressure <90 mmHg (32/68, 47% versus 86/136, 63%, respectively, P = 0.02) or urinary catheterization (32/68, 47% versus 90/136, 66%, respectively, P = 0.005), while the KPC/Kp bacteraemia group had a greater incidence of acute renal failure (45/68, 66% versus 67/136, 49%, respectively, P = 0.02). There was no difference between the two groups in duration of hospitalization. The mortality rate of the KPC/Kp bacteraemia group was 44/68 (65%) compared with 54/136 (40%) in the ESBL/Kp bacteraemia control group (P = 0.008), which in the multivariate analysis remained highly significant (P < 0.001). Only 11/68 (16%) of KPC/Kp patients were functionally independent at discharge compared with 43/136 (32%) ESBL/Kp patients (P = 0.012). CONCLUSIONS The selection of an ESBL/Kp control cohort with a ratio of 1:2 (study versus control group) helped resolve an as yet insufficiently settled question: bacteraemia with KPC/Kp is an independent risk factor for death, justifying the strict adherence to cohorting and isolation procedures.

Initial Effects of the National PCV7 Childhood Immunization Program on Adult Invasive Pneumococcal Disease in Israel

Background PCV7 was introduced as universal childhood vaccination in Israel in July 2009 and PCV13 in November 2010. Here we report data on adult invasive pneumococcal disease (IPD), two years post PCV7 implementation and before an expected effect of PCV13. Methods An ongoing nationwide active-surveillance (all 27 laboratories performing blood cultures in Israel), providing all blood & CSF S. pneumoniae isolates from persons >18 y was initiated in July 2009. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. IPD outcome and medical history were recorded in 90%. Second year post PCV implementation is compared to the first year. Results During July 2009 to June 2011, 970 IPD cases were reported (annual incidence [/100,000] of 9.17 and 10.16 in the two consecutive years, respectively). Respective case fatality rates (CFRs) were 20% and 19.1%. Incidence of IPD and CFR increased with age and number of comorbidities. Incidence rate was significantly greater during the second winter, 7.79/100,000 vs. 6.14/100,000 in first winter, p = 0.004, with a non-significant decrease during summer months (3.02 to 2.48/100,000). The proportion of IPD cases due to PCV7-serotypes decreased from 27.5% to 13.1% (first to second year) (p<0.001). Yet, non-PCV13-strains increased from 32.7% to 40.2% (p = 0.017). The increase in non-PCV13-strains was highly significant in immunocompromised patients and to a lesser degree in non-immunocompromised at risk or in older patients (>64 y). Among younger/healthier patients serotype 5 was the major increasing serotype. Penicillin and ceftriaxone resistance decreased significantly in the second year. Conclusions While overall annual incidence of IPD did not change, the indirect effect of PCV7 vaccination was evident by the significant decrease in PCV7 serotypes across all age groups. Increase in non-VT13 strains was significant in immunocompromised patients. A longer follow-up is required to appreciate the full effect of infant vaccination on annual IPD.

Antiphospholipid antibodies during infectious mononucleosis and their long term clinical significance

BACKGROUND The prevalence of antiphospholipid antibodies (aPLs) during acute Epstein-Barr virus (EBV) infection may be as high as 30-60%. The role of these autoantibodies in the development of antiphospholipid syndrome (APS) is not clear. OBJECTIVE To investigate the prevalence, persistence and clinical significance of aPLs in a series of patients diagnosed with acute EBV infection. STUDY DESIGN A cohort of 94 patients aged 15 or older, recently diagnosed with acute EBV was retrieved. Serum samples obtained during diagnosis were tested for the presence of aPLs and anti-β2GP antibodies. Patients with positive sera for aPLs were assessed for the persistence of aPLs and the development of APS. RESULTS The prevalence of aPLs among 94 patients with acute EBV was 37.2%. Five of 27 available serum samples were also positive for anti-β2 glycoprotein (anti-β2GP) antibodies. Repeat testing for aPLs after a median of 21 months post acute infection (range 13-50 months) was performed in 17 of the 35 patients with positive aPL test. All 17 patients were found negative for aPL-IgG antibodies. Two of them had positive aPL-IgM antibodies and positive anti-β2GP antibodies. None of the patients who had positive aPLs experienced any manifestations of APS. CONCLUSION The disappearance of aPLs in the majority of the patients after acute EBV infection, along with the absence of consistent clinical findings, suggests that the detection of aPLs during acute EBV is not associated with the development APS over time.

The cellular immunological responses of patients undergoing coronary artery bypass grafting compared with those of patients undergoing valve replacement

OBJECTIVE Major surgical intervention such as cardiac surgery has been shown to have profound effects on the immune system. We conducted a prospective study comparing the effects of coronary artery bypass grafting (CABG) versus isolated valve surgery. METHODS Blood samples were drawn from 59 patients undergoing either elective CABG or elective isolated valve replacement surgery. Samples were obtained preoperatively and on the first and third postoperative days. Total cell counts and differential counts were recorded. Several cellular immunity parameters were determined by flow cytometry. RESULTS On all postoperative days, significant increases in white blood cell (WBC) and monocyte counts were observed. Significant decreases in all lymphocyte populations were also observed with similar decreases in both helper (CD4) and suppressor (CD8) T cells. An increase in activated T cells was noted on day 1, returning to normal on the third postoperative day. Despite the significant decrease in human leucocyte antigen-DR (HLA-DR) antigen expression on monocytes on both the first and third postoperative days, a significant increase in monocyte activation as represented by increased CD11b and CD64 expression was detected. No significant difference was found for any of the measured parameters between the CABG group and the valve replacement group. Eight patients developed early wound infections, with no correlation with any of the measured parameters, including magnitude and duration of decrease in HLA-DR antigen expression on monocytes. CONCLUSIONS Cardiac surgery induces both a state of pro-inflammation and of immune suppression. The two major types of cardiac surgery induce similar effects to the immune system. None of the measured parameters was predictive for development of postoperative wound infection.