Modifiable risk factors associated with later gut decolonization of carbapenem-resistant Gram-negative bacteria in children: a prospective cohort study.

BACKGROUND: Nosocomial infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB) are associated with increased mortality and prolonged hospitalization; thus, later CRGNB decolonization has significant clinical and public health implications. AIM: To investigate modifiable/non-modifiable risk factors for CRGNB later gut decolonization in children. METHODS: CRGNB carriers (aged from one day to 16 years) hospitalized in a tertiary level hospital (2018-2019) were included. Upon CRGNB carriage detection, rectal swab cultures were taken weekly, if patients were hospitalized, and monthly after discharge for 12 months. CRGNB decolonization was defined as three consecutive negative rectal-swab cultures obtained ≥1 week apart. Modifiable (treatment administered/medical devices) and non-modifiable (age/gender/comorbidities) risk factors were recorded. Cox regression for later CRGNB decolonization was performed. FINDINGS: One hundred and thirty CRGNB carriers were recorded. After 12 months, 5.4% remained carriers. Risk factors for later decolonization were immunosuppression (hazard ratio: 0.52; 95% confidence interval: 0.31-0.87), carbapenems (0.52; 0.30-0.91), proton pump inhibitors (PPIs) (0.39; 0.24-0.64) and their duration of use, duration of hospitalization (0.90; 0.81-0.92, per 10 days), number of readmissions (0.90; 0.86-0.96), abdominal surgery (0.33; 0.17-0.65), urinary catheter (0.42; 0.24-0.76), and duration of steroid administration per 10 days (0.86; 0.84-0.88). CONCLUSIONS: Carbapenems, PPIs and their duration of use, duration of steroids use, immunosuppression, urinary catheter, readmissions, duration of hospitalization, and abdominal surgery are associated with later CRGNB decolonization among children. Paediatric patients at risk of later decolonization should be under targeted screening and pre-emptive contact precautions. Known carriers at risk of later CRGNB decolonization should be under meticulously applied contact precautions for longer durations.

Colonization and Infection With Extensively Drug Resistant Gram-Negative Bacteria in Liver Transplant Recipients.

BACKGROUND: Infections due to extensively drug resistant Gram-negative bacteria (GNB) after solid organ transplantation are increasing in prevalence and are associated with high morbidity and mortality. Surveillance culture (SC) seems to be an important tool for extensively drug resistant GNB control. The aim of this study was to evaluate colonization rates and subsequent infections by XDR-GNB in liver transplant recipients. MATERIAL AND METHODS: This was a prospective cohort study in patients who underwent liver transplantation (LT) between January 2016 and January 2018. Data on demographics, extensively drug resistant colonization, and 3-month clinical outcomes were obtained. Colonization was defined as a positive surveillance culture (SC-perirectal) immediately before transplantation, once weekly after LT, and after intensive care unit discharge, with emphasis to carbapenem-resistant Gram-negative bacteria (CR-GNB). RESULTS: Forty-four patients who underwent LT were included in the study. Ten patients (22.72%) were colonized with CR-GNB prior to transplantation, and 7/10 (70%) developed infection due to the same pathogen (5 patients bloodstream infections, 2 patients pneumonia) during the study period. Intensive care unit length of stay was significantly longer in colonized with CR-GNB patients (P < .05). Mortality rate was higher in colonized patients (30%) than in noncolonized (11.76%) (P = .2). CONCLUSION: Our study results suggest an overall 70% risk of CR-GNB infection among colonized patients. Given the high mortality rate and the difficulty in treating these infections, further research to investigate and develop strategies to eliminate the colonization is needed.

Perioperative Chemoprophylaxis οr Treatment for Extensively Drug Resistant Gram-Negative Bacteria in Patients Undergoing Liver Transplantation Based on Preoperative Donor/Recipient Surveillance Cultures: A Prospective Study.

INTRODUCTION: The importance of preoperative donor/recipient colonization or donor infection by extensively drug-resistant Gram-negative bacteria (XDR-GNB) and its relation to serious post-transplantation infection pathogenicity in liver transplantation (LT) patients has not been clarified. AIM: Prevention of postoperative infection due to XDR-GNB with the appropriate perioperative chemoprophylaxis or treatment based on preoperative donor/recipient surveillance cultures in LT patients, as well as their outcome. MATERIALS AND METHOD: Twenty-six patients (20 male, 6 female) were studied (average preoperative Model for End-Stage Liver Disease score ≈15, range: 8-29) from January 2017 to January 2018. In all patients, blood, urine, and bronchial secretions culture samples as well as a rectal colonization culture were taken pre- and postoperatively, once weekly after LT, and after intensive care unit discharge. Recipients with positive XDR-GNB colonization and patients receiving a transplant from a donor with an XDR-GNB positive culture or colonization received the appropriate chemoprophylaxis one half hour preoperatively according to culture results. De-escalation of the antibiotic regimen was done in 2 to 5 days based on the colonization/culture results of the donor and recipient and their clinical condition. Evaluation for serious infection was done at 1 week and at 28 days for outcome results. RESULTS: Fourteen out of 26 recipients (53.8%) were positive for XDR-GNB colonization preoperative, with 2/14 (14.28%) presenting serious infection due to the same pathogen. Intensive care unit length of stay was significantly longer in colonized with XDR-GNB patients (P < .0001). The outcome of colonized patients was 6/14 (42.8%) expired, but only in 2/14 (14.2%) was mortality attributable to infection. CONCLUSION: Administering appropriate perioperative chemoprophylaxis and treatment may limit the frequency of XDR-GNB infections and intensive care unit length of stay and may improve the outcome in LT recipients.

Development of case vignettes for assessment of the inter-rater variability of national validation teams for the point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals.

BACKGROUND: In 2016-17 the European Centre for Disease Prevention and Control (ECDC) organized the second point prevalence survey (PPS) of healthcare-associated infections (HCAIs) and antimicrobial use in European acute care hospitals. This survey included a validation study to maximize the accuracy of case identification and classification. AIM: ECDC developed case vignettes to assess the performance of the national validation teams. METHODS: Case vignettes were developed by two medical doctors with experience in the management of HCAIs and antimicrobial stewardship. The case vignettes were based on actual clinical cases. The distribution of HCAIs among the case vignettes reflected the distribution of HCAIs in the previous PPS. All case vignettes were pilot-tested by three expert raters. Agreement among the expert raters was measured using kappa statistics. FINDINGS: Sixty case vignettes were developed. Twenty-nine of them were HCAI cases and 31 were cases without an HCAI. The inter-rater reliability using kappa statistics was 0.78 for the presence of HCAI and 0.89 for the antimicrobial use, respectively. CONCLUSION: The agreement between the expert raters was very good for antimicrobial use and good for the presence of HCAI. Case vignettes can be a tool to support standardization of surveillance, improving the validity and comparability of the data.

Establishing nationally representative central line-associated bloodstream infection surveillance data for paediatric patients in Greece.

BACKGROUND: Healthcare-associated infections (HCAIs) are associated with increased morbidity and mortality and with excess costs. Central line-associated bloodstream infections (CLABSIs) are the most common HCAIs in neonates and children. AIM: To establish national benchmark data for rates of CLABSI in neonatal and paediatric intensive care units (NICUs and PICUs) and paediatric oncology units (ONCs). METHODS: Active surveillance for CLABSI was conducted from June 2016 to February 2017. A collaborative of 14 NICUs, four PICUs, and six ONCs participated in the programme. Surveillance definitions of central line (CL), central line utilization (CLU) ratio, CLABSI event, and CLABSI rate were based on the Centers for Disease Control and Prevention's 2014 National Healthcare Safety Network criteria. Medical records were assessed daily for calculating CL-days, patient-days, and susceptibility of isolated organisms. FINDINGS: A total of 111 CLABSI episodes were recorded. The overall mean CLABSI rate was 4.41 infections per 1000 CL-days, and the CLU ratio was 0.31. CLABSI rates were 6.02 in NICUs, 6.09 in PICUs, and 2.78 per 1000 CL-days in ONCs. A total of 123 pathogens were isolated. The most common pathogens were Enterobacteriaceae (36%), followed by Gram-positive cocci (29%), non-fermenting Gram-negative bacteria (16%), and fungi (16%). Overall, 37% of Gram-negative pathogens were resistant to third-generation cephalosporins and 37% to carbapenems. CONCLUSION: Nationally representative CLABSI rates were determined for paediatric patients. These data could be used to benchmark and serve as baseline data for the design and evaluation of infection control and antimicrobial stewardship interventions.

Impact of active surveillance and infection control measures on carbapenem-resistant Gram-negative bacterial colonization and infections in intensive care.

BACKGROUND: Carbapenem-resistant Gram-negative bacteria (CRGNB) infections constitute a global threat for critically ill patients and the outcome of their hospitalization. Early identification of CRGNB through rectal surveillance cultures and routine infection control measures including contact precautions, use of appropriate disinfectants, staff education on cleaning, and hand hygiene may reduce the dissemination of CRGNB. AIM: To assess the impact of enhanced infection control measures on CRGNB infections in a nine-bed polyvalent intensive care unit in a tertiary level hospital in an endemic area. METHODS: A quasi-experimental study, which included patients with CRGNB infection retrospectively for six months and those participating in an active surveillance programme prospectively for the subsequent 22 months. Active surveillance programme (weekly rectal swabs) was implemented including two sub-periods with infection control measures and enhanced infection control measures. CRGNB incidence, prevalence, colonization pressure, infections and compliance with infection control measures and enhanced infection control measures were recorded. Analysis was performed through time-series and interrupted time-series. FINDINGS: During the active surveillance programme, enhanced infection control measures led to a steeper downwards trend in incidence, prevalence, and colonization pressure for CRGNB compared to the infection control measures sub-period. The linear trend was for carbapenem-resistant Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) infections to decrease from 19.6 to 8.1 infections per 1000 bed-days (IBD) (P = 0.001) and from 5.1 to 1.79 IBD (P = 0.043), respectively. By contrast, carbapenem-resistant Acinetobacter baumannii infections increased from 5.2 to 15.3 IBD (P = 0.001). CONCLUSION: Enhanced infection control measures including enhanced hand hygiene, active surveillance combined with contact precautions, education, audits and feedback policies and interventions could reduce CRKP and CRPA in endemic areas.

Bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae among intensive care unit patients after orthotopic liver transplantation: risk factors for infection and impact of resistance on outcomes.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as an important cause of bloodstream infections in intensive care units (ICUs). The aim of this study was to determine risk factors for bloodstream infections caused by CRKP as well as risk factors for CRKP-associated mortality among ICU patients after orthotopic liver transplantation (LT). METHODS: The study cohort of this observational study comprised 17 ICU patients after LT with CRKP bloodstream infections. The data from these patients were matched with 34 ICU patients (1:2) after LT without CRKP infections. The 2 groups were compared to identify risk factors for development of CRKP infection and risk factors for mortality. RESULTS: Seventeen CRKP bloodstream infections occurred in ICU patients after LT from January 1, 2008, to December 31, 2011. In univariate analysis, primary liver disease and especially hepatitis C virus infection or hepatocellular cancer were significant factors for development of CRKP. Acute Physiology and Chronic Health Evaluation (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score as well as CRKP bloodstream infection were predictors for ICU death (P < .05) in univariate analysis. CONCLUSIONS: CRKP bloodstream infections affect immunocompromised post-transplantation patients more. Bloodstream infections with CRKP along with APACHE and SOFA scores were predictors of death in ICU patients after LT.

Tigecycline for treatment of carbapenem-resistant Klebsiella pneumoniae infections after liver transplantation in the intensive care unit: a 3-year study.

BACKGROUND: This 3-year prospective, observational, single-center study was undertaken to describe prescription, microbiology findings, tolerance, and efficacy of tigecycline for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections after liver transplantation in the intensive care unit (ICU). METHODS: All patients after liver transplantation treated with tigecycline for ≥3 days for CRKP infections in our ICU from January 1, 2010, to December 31, 2012, were studied. Patient characteristics, indication of treatment, bacteriology, and ICU mortality were collected. The main end points were clinical and microbiologic efficacy and tolerance of tigecycline. RESULTS: Over the study period, 8 men and 2 women (18 CRKP isolates), aged 54.3 ± 7.7 years, were included in the study. Acute Physiology and Chronic Health Evaluation and Sequential Organ Failure Assessment scores on ICU admission were 13.7 ± 2.7 and 10 ± 2.2, respectively. In 7 isolates, tigecycline was prescribed for CRKP blood stream infection (BSI), in 6 for complicated intra-abdominal infection (IAI), in 2 for ventilator-associated pneumonia (VAP), in 2 for surgical site infection, and in 1 for urinary tract infection. In 4 cases, tigecycline was prescribed for secondary BSI followed by VAP and/or IAI. All isolates were susceptible to tigecycline, 83.4% to colistin, 44.5% to gentamicin, and 27.8% to amikacin. In 2 patients, tigecycline was prescribed as monotherapy. Three patients had clinical failure. The microbiologic response rate was 70%. Superinfection was detected in 5 patients, and Pseudomonas aeruginosa was the most frequently isolated pathogen. Tigecycline was generally well tolerated. The ICU mortality rate was 60% with attributable mortality rate 30%. CONCLUSIONS: Our pilot study suggests that tigecycline shows a good safety and tolerance profile in patients with CRKP infections in the ICU after orthotopic liver transplantation. Limited therapeutic options for such infections leave physicians no choice but to use tigecycline for off-label indications such as urinary tract and blood stream infections.

Course and outcome of renal transplant recipients admitted to the intensive care unit: a 20-year study.

BACKGROUND: Renal transplantation represents the main treatment for end-stage renal disease. The goal of this study was to evaluate the course and outcome of renal transplant recipients admitted to the intensive care unit (ICU) and to analyze factors determining prognosis and mortality. METHODS: The demographic features, data admission characteristics, and ICU courses of all renal transplant recipients admitted to our ICU from 1992 to 2012 were evaluated to analyze factors for mortality. RESULTS: Eleven women and 50 men of mean age 45.5 ± 12.5 years were included in the study. Acute Physiology And Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores on ICU admission were 20 ± 5.7 and 8.5 ± 3.5, respectively. The main reasons for admission were as follows: sepsis (n = 27) or immediate postoperative complications (n = 16). Thirty-five patients during their ICU stay required hemodialysis and 34 needed catecholamines. The mortality rate was 42.6%. APACHE II Score, dialysis requirement, and sepsis as a reason for ICU admission were independently related to the mortality. CONCLUSIONS: The mortality rate was higher than that of the general ICU population (42.6% vs 30%). The main reason for ICU admission of renal transplant recipients was sepsis.

Infections related to renal transplantation requiring intensive care admission: a 20-year study.

INTRODUCTION: The aim of this study was to evaluate infection complications as the reason for intensive care unit (ICU) admission among transplant recipients. METHODS: We studied all renal transplant recipients with infectious complications admitted to our ICU from 1992 to 2012:44.3% of all renal transplant recipients admitted to ICU. The epidemiology and prognosis of infectious complications requiring ICU admission were evaluated with analysis of mortality factors. RESULTS: The 22 men and 5 women included in this study showed a mean age of 42.7 ± 12.3 years. The Acute Physiologic and Chronic Health Evaluation II and Seguential Organ Failure Assessment scores on ICU admission were 20 ± 4.6 and 8.6 ± 3.9, respectively. The main infections complications requiring ICU admission were cytomegalovirus pneumonia (n = 15) and aspergillus pneumonia (n = 4). Sixteen patients required hemodialysis and 14, catecholamine support upon ICU admission owing to septic shock. The mortality rate among study patients was 62.9%, versus 26.5% for noninfectious renal transplant recipients requiring ICU admissions. Catecholamine support at ICU admission was independently related to mortality. CONCLUSION: The mortality rate of renal transplant recipients admitted to ICU owing infection complications was higher than that of noninfected renal transplant patients. These data suggest that infections and septic shock in renal transplant recipients requiring ICU admission worsen their outcome significantly.

Microbiological and molecular characteristics of carbapenemase-producing Klebsiella pneumoniae endemic in a tertiary Greek hospital during 2004-2010.

We report 570 carbapenemase-producing Klebsiella pneumoniae (CPKP) clinical isolates in a 1,040-bed Greek tertiary hospital during 2004 to 2010. The first CPKP (VIM-producing) was isolated in September 2004. Despite initial containment, VIM producers have become endemic since 2006. KPC-producing K. pneumoniae was first isolated in August 2007 from a patient who came from Israel, spread rapidly, and outcompeted VIM. Overall, 267 (47%) VIM-producing and 301 (53%) KPC-producing strains were isolated, including 141 (24.7%) from patients with bacteraemia. Two isolates carrying both VIM and KPC were isolated in two consecutive months in 2009, but not since. The prevalence of CPKP increased from 0% in 2003 to 38.3% in 2010 (p<0.0001). All genotyped KPC producers harboured blaKPC-2 and belonged to two clones, among which the hyperepidemic Greek clone, related to those from the United States and Israel, predominated. Most metallo-beta-lactamase (MBL) producers carried the blaVIM-1 gene and belonged to several clones, whereas all but one isolate with blaVIM-12 were clustered within a five-month period, arising from one clone. Resistance to non-beta-lactam antibiotics was also increased among CPKP. They were almost invariably resistant to ciprofloxacin and trimethoprim-sulfamethoxazole. Resistance to colistin increased from 3.5% (4/115) in 2008 to 20.8% (25/120) in 2010, and resistance to tigecycline also increased. Following reinforcement of infection control measures, prevalence of CPKP (mainly KPC) has been reduced since mid-2009 (from 46% in 2009 to 38.3% in 2010). In view of the exhaustion of available therapies, investment in infection control resources and optimal antibiotic use is urgently required.

Serum levels of daptomycin in pediatric patients.

BACKGROUND: Limited data are available on the pharmacokinetics and optimal dosage of daptomycin, a lipopeptide compound possessing activity against Gram-positive bacteria, in the pediatric population, particularly in neonates and infants. We determined serum levels of daptomycin in hospitalized pediatric patients treated with various dosages of this agent. METHODS: Blood samples were obtained from pediatric patients of all ages with normal renal function who had received daptomycin between May 2009 and December 2010. Serum levels prior ("trough") and 30 min after end of the infusion ("peak") were determined using an ultra-performance liquid chromatography-UV detection method. RESULTS: A total of four daptomycin dosages and four patients were studied. Three patients were infants (gestational age: 29-38 weeks, age at sampling 26-65 days) and the fourth was a 7-year-old boy. A dosage of 6 mg/kg/12 h of daptomycin to the infants resulted in trough concentrations of <4-8.4 mg/l and peak concentrations of 10.9-17.7 mg/l. Comparable levels were observed after one of the infants received a dosage of 11 mg/kg/12 h, while a further dosage increase to 15 mg/kg/12 h yielded peak concentrations of 35.5 mg/l. The 7-year-old child received a daptomycin dosage of 12 mg/kg once daily; trough and peak levels were 4.2 and 103.4 mg/l, respectively. CONCLUSIONS: A dosage of daptomycin 6 mg/kg/12 h in small infants results in lower peak and similar trough concentrations compared with a dosage of 4 mg/kg/day administered to adults. This results suggests that daptomycin dosages of more than 6 mg/kg/12 h may be needed for this pediatric age group to achieve a similar drug exposure as adults.