Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients.

Background: Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSIs) are associated with significant mortality. Daptomycin exhibits concentration-dependent activity vs VRE in vitro, yet the clinical impact of higher-dose strategies remains unclear. Methods: We performed a national retrospective cohort study of hospitalized Veterans Affairs patients treated with standard-dose (6 mg/kg total body weight), medium-dose (8 mg/kg total body weight), or high-dose (≥10 mg/kg total body weight) daptomycin for VRE-BSI. Patient-related, microbiological, and outcomes data were abstracted from clinical databases. The primary outcome was overall survival, evaluated by Cox regression. Secondary outcomes included 30-day mortality, time to microbiological clearance, and creatine phosphokinase (CPK) elevation. Results: A total of 911 patients were included (standard dose, n = 709; medium dose, n = 142; high dose, n = 60). Compared to high-dose daptomycin, both standard-dose (hazard ratio [HR], 2.68; 95% confidence interval; [CI], 1.33-3.06; P = .002) and medium-dose (HR, 2.66; 95% CI, 1.33-3.92; P = .003) daptomycin were associated with poorer survival. After adjusting for confounders, the relationship between poorer survival and standard-dose (adjusted HR [aHR], 2.58; 95% CI, 1.27-4.88; P = .004) and medium-dose (aHR, 2.52; 95% CI, 1.27-5.00; P = .008) daptomycin persisted. Thirty-day mortality was significantly lower among high-dose daptomycin-treated patients compared with other dosing strategies (risk ratio, 0.83; 95% CI, .74-.94; P = .015). Compared with standard-dose daptomycin, both medium-dose (HR, 0.78; 95% CI, .55-.90; P = .012) and high-dose daptomycin (HR, 0.70; 95% CI, .41-.84; P = .006) were associated with significantly improved microbiological clearance. No difference in the risk of CPK elevation was observed between the treatment groups (P = .504). Conclusions: High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.

ESBL-producing Escherichia coli isolated from bloodstream infections--antimicrobial susceptibility, conjugative transfer of resistance genes and phylogenetic origin.

BACKGROUND: The prevalence of bloodstream infections (BSIs) due to ESBL-producing Escherichia coli (ESBL-EC) strains has increased dramatically over the past years. OBJECTIVES: Characterization of ESBL-EC isolates collected from BSIs with regard to their antimicrobial susceptibility and phylogenetic background. The conjugative transfer of resistance determinants to the E. coli reference strain K12 C600 was also investigated. MATERIAL AND METHODS: A collection of forty-eight ESBL-EC strains recovered from BSIs was subjected to the study. These strains were obtained from the ICU (intensive care unit) of the Medical University Hospital, Wroclaw, Poland, during a four-year period (2009-2012). All the isolates were screened for ESBL production by the double disk synergy test (DDST). Transferability of plasmid-mediated resistance genes was performed by the conjugational broth method. Susceptibility to antibiotics and chemotherapeutics of clinical isolates and transconjugants was determined by the agar dilution method. PCR assay was used to detect the blaCTX-M gene in ESBL-EC tested and transconjugants. Affiliation to phylogenetic groups was done by the triplex PCR method. RESULTS: Conjugational transfer of plasmids responsible for ESBL to a recipient strain was successful for all the ESBL-EC analyzed (donors). The conjugation frequencies ranging from 2.3×10(-7) to 5.2×10(-1) per donor. In vitro susceptibility testing revealed that all the ESBL-EC isolates and their transconjugants were resistant to most of the antimicrobial agents tested with the exception of carbapenems, tigecycline, and ß-lactam-clavulanate combinations. Moreover, all the donor strains and their transconjugants were found to contain the blaCTX-M gene. The majority of the isolates analyzed belonged to phylogroups B2 (62.5%) and D (25%), whereas groups B1 and A were less frequently represented (8.3% and 4.2%, respectively). CONCLUSIONS: The results of the study confirm the need of antibiotic policies and effective infection control measures in hospital settings to minimize BSIs caused by multi-resistant ESBL-producing pathogens.

Risk factors for urinary tract infections due to ciprofloxacin-resistant Escherichia coli in a tertiary care urology department in Switzerland.

QUESTIONS UNDER STUDY: Monitoring of antimicrobial resistance is a key component of antibiotic stewardship programs. In 2007, a significantly higher resistance rate of Escherichia coli to ciprofloxacin was found at the Department of Urology, University Hospital Zurich, Switzerland, when compared to other hospital units. Thus, we aimed to determine the risk factors for this increased fluoroquinolone resistance in outpatients and inpatients with urinary tract infection (UTI) or colonisation with E. coli. METHODS: We performed a cross sectional study including 275 patients of the Department of Urology in whom E. coli was isolated from urine or blood cultures between 01.01.2006 and 31.08.2007. Clinical data were collected from patients' records using a structured questionnaire. Multivariable analysis was performed for the detection of risk factors. RESULTS: Ciprofloxacin-resistant E. coli was detected in 22% of patients. Risk factors for ciprofloxacin-resistant E. coli included prior use of fluoroquinolones (odds ratio [OR] (95% confidence intervals): 2.24 (1.08-4.62), p = 0.030), prior urinary tract catheterisation (OR: 2.41 (1.02-5.67), p = 0.044) and recurrent UTIs (OR: 2.26 (1.07-4.78), p = 0.032). 60.8% of all prescriptions in urinary tract infections were for fluoroquinolones, and this antibiotic class was the empiric antibiotic regimen of choice in 72.5% of all acute, uncomplicated, urinary tract infections. CONCLUSIONS: The increasing prevalence of ciprofloxacin-resistant E. coli makes empiric therapy in UTIs with this agent questionable, especially in patients with one or several of the above mentioned risk factors. Due to the increasing resistance rate, continuous surveillance and susceptibility testing in individual patients, particularly with complicated UTIs, is indispensable for adequate therapy.

Almond oil implicated in a Staphylococcus capitis outbreak in a neonatal intensive care unit.

OBJECTIVE: To develop an effective outbreak-control strategy by identifying the source and modes of transmission of Staphylococcus capitis in a 60-bed neonatal intensive care unit (NICU). STUDY DESIGN: We conducted a study among neonates hospitalized during the outbreak (June 2000 through November 2003). All cases of S. capitis colonization or infection detected by clinical samples during the outbreak were included. The molecular analysis of the isolated was assessed by pulsed-field electrophoresis. We reported the description of the outbreak and the measures taken during this investigation. RESULT: Thirty-three patients were colonized or infected by S. capitis. Mean gestational age was 28.5+/-4.4 weeks of gestation, mean birth weight was 1068+/-637.3 g and the mean length of hospital stay was 77.9+/-35.9 days. We observed that positive S. capitis cultures were over-represented in six beds of the NICU. Because S. capitis is known to thrive in lipid media, we cultured samples from the almond oil bottles assigned to these beds. S. capitis strain recovered from one of the almond oil sample was genetically identical to the strain recovered from the cases. CONCLUSION: Almond oil is an unusual reservoir infection. Control policy allowed prompt institution of measures that were successful in ending the outbreak.

Genotypic analysis of Acinetobacter bloodstream infection isolates in a Turkish university hospital.

Acinetobacter baumannii is a significant pathogen of bloodstream infections in hospital patients that frequently causes single clone outbreaks. We aimed to evaluate the genetic relatedness and antimicrobial susceptibility of Acinetobacter spp. bloodstream isolates, in order to obtain insight into their cross-transmission. This prospective study was conducted at the Erciyes University Hospital. During a 1-y period, all patients with nosocomial BSI caused by Acinetobacter spp. were included in the study. All data with regard to the patients, underlying diseases and risk factors for BSI and the severity of disease were collected. Blood culture isolates of Acinetobacter spp. were identified according to their morphology and biochemical reactions. The antimicrobial susceptibility was determined using the Kirby-Bauer disk diffusion test according to the NCCLS; the genetic relatedness of isolates was determined by RAPD-PCR analysis and pulsed-field gel electrophoresis (PFGE). 41 patients acquired a nosocomial bloodstream infection caused by A. baumanii during this period. 88% of these infections (36 of 41) occurred while the patients were treated in the intensive care unit. Nearly 80% of the isolates belonged to 3 genotypes, suggesting cross-transmission in ICU settings where infection control practices are poor. All Acinetobacter isolates were multidrug-resistant and the crude mortality of patients infected with A. baumanii was 80.5%. We concluded that the genetic relatedness of Acinetobacter spp. causing BSI was very high, indicating cross-transmission within the ICU setting. Essential components of an infection control programme to prevent nosocomial transmission of A. baumannii are early detection of colonized patients, followed by strict attention to standard precautions and contact isolation.

Neonatal early onset Escherichia coli sepsis: trends in incidence and antimicrobial resistance in the era of intrapartum antimicrobial prophylaxis.

BACKGROUND: Although intrapartum antimicrobial prophylaxis has lowered the incidence of early onset group B Streptococcus (GBS) sepsis, there are concerns that the increased use of antibiotics may raise the incidence of non-GBS antimicrobial-resistant infections. The objective of this study was to determine trends in the incidence and antimicrobial resistance of early onset sepsis caused by Escherichia coli in the era of antimicrobial prophylaxis. METHODS: All neonates with early onset E. coli infection who were born at La Paz Hospital, Madrid, from January 1, 1992, through December 31, 2002, were identified from a microbiologic register of all neonatal infections. To evaluate the effect of the guidelines for GBS prevention, data were pooled and compared for: 1992 through 1995 (Period 1); 1996 through 1998 (Period 2); and 1999 through 2002 (Period 3). RESULTS: Early onset E. coli infection was diagnosed in 41 of 84 612 live births. The infection rate did not change significantly during the 3 time periods (0.56, 0.24 and 0.55 per 1000 during Periods 1, 2 and 3, respectively; P = 0.936, linear-by-linear association). The proportion of E. coli infections that were resistant to ampicillin increased significantly among preterm infants, from 25% (1 of 4) in Period 1, to 100% (2 of 2) in Period 2 and to 91% (10 of 11) in Period 3 (P = 0.017, linear-by-linear association), but not among term infants, with 67% (8 of 12) in Period 1, 50% (1 of 2) in Period 2 and 44% (4 of 5) in Period 3 (P = 0.317, linear-by-linear association). CONCLUSIONS: Although the incidence of early onset sepsis caused by E. coli remained stable during the study period, antibiotic-resistant E. coli infections increased among preterm infants. On the whole these trends are reassuring with respect to GBS prophylaxis. However, the increase in the proportion of ampicillin-resistant infections in preterm infants suggests that continuing evaluation of the risks and benefits of prophylaxis in this group is critical.

Investigations of Enterococcus faecalis-induced bacteraemia in brown layer pullets through different inoculation routes in relation to the production of arthritis.

In the present aerosol experiment, assessment of the respiratory tract of 1-day-old birds as a natural route of infection for induction of Enterococcus faecalis bacteraemia and arthritis was performed. Second, the severity and type of arthritis produced through intramuscular infection in two different inoculation sites (musculus pectoralis versus musculus gastrocnemius) was studied. Third, the resulting bacteraemia was assessed qualitatively and quantitatively in relation to the occurrence of arthritis. Exposure of 1-day-old brown layer pullets to aerosolized E. faecalis with an estimated uptake of 10(4) to 10(5) colony forming units per chick resulted in bacteraemia; however, joint lesions were not induced. In contrast, 3/10 birds inoculated intratracheally with 10(8) colony forming units developed both bacteraemia and arthritis. This suggests the occurrence of a dose effect and a role for the respiratory tract as a natural infection route in young chickens. In both intramuscularly inoculated groups the incidence of arthritis was 10/10 birds and 9/10 birds, respectively. Birds inoculated in the m. pectoralis developed symmetric polyarthritis, which harmonizes with haematogenous colonization of joints. In contrast, m. gastrocnemius-inoculated chicks mostly had asymmetric (poly)arthritis of the injected leg and varus deformation of the contralateral leg, suggesting predominantly local spread. The qualitative and quantitative results of bacteriology of blood samples show that arthritis develops in those groups with the highest number of bacteraemic birds and the highest median bacterial colony forming units per millilitre of blood during the first 24 to 36 h after treatment.

Mechanisms of severe transfusion reactions.

Serious adverse effects of transfusion may be immunologically or non-immunologically mediated. Currently, bacterial contamination of blood products, particularly platelets, is one of the most significant causes of transfusion-related morbidity and mortality. Septic transfusion reactions can present with clinical symptoms similar to immune-mediated hemolytic transfusion reactions and transfusion-related acute lung injury. Extremely high fever and/or gastrointestinal symptoms, in a transfusion recipient, may be indicative of sepsis. The diagnosis is based upon culturing the same organism from both the patient and the transfused blood component. Numerous organisms have been implicated as the cause of septic transfusion reactions. Due to different storage conditions, gram negative organisms are more often isolated from red blood cell components; gram positive organisms are more often isolated from platelets. Prevention of septic transfusion reactions is primarily dependent on an adequate donor history and meticulous preparation of the donor phlebotomy site. Visual inspection of blood components prior to transfusion is also vital to preventing these reactions. Several methods of detection of bacterial contamination and inactivation of pathogens are currently under active investigation.

Bacterial contamination of blood products: factors, options, and insights.

Transfusion of bacterially contaminated blood products remains an overlooked problem. However, the risk of receiving a bacterially contaminated unit is greater than the combined risk of HIV-1/2, HCV, HBV, and HTLV I/II [American Association of Blood Banks Bulletin, no. 294, 1996]. Topics covered in this article include: the current incidence, clinical presentation and outcome, effective methods of detection, and ways to reduce bacterial contamination of blood products. There is no one existing strategy that can completely eliminate the risk of bacterial contamination. It is inevitable that partial solutions or combinations of methods will be implemented in the near future.

Current status of bacterial contamination of autologous blood for transfusion.

Autologous transfusion, although not without risk, does decrease the risk of transmitted diseases via homologous transfusion. However, strict quality control is required for autologous transfusion. In Japan, a recent enactment requires that written informed consent be obtained prior to blood transfusion, which therefore requires that clinicians provide sufficient explanation of the risks involved with this procedure. To the best of our knowledge, this is the first study to comprehensively evaluate the manner in which the safety of autologous blood transfusion can be compromised by bacterial contamination. For a 24-month period, between April 1996 and March 1998, bacterial contamination of all kinds of autologous blood samples was tested by sampling the culture immediately prior to transfusion. Subculturing, identification and susceptibility testing of the isolates were performed. From the 287 units of all kinds of autologous blood transfused, 18 were culture positive (6.3%). Positive blood cultures were obtained in two of the 59 units (3.4%) of autologous transfusion donated preoperatively (ATDP) that was infused intraoperatively, in three of the 117 units (2.6%) of hemodilution/autologous transfusion (HAT) and in three of the 81 (3.7%) of ATDP infused postoperatively. There was a high percentage (33.3%) of positive blood cultures in the cases of intraoperative blood salvage (IOBS). The total rate of positive blood cultures was 6.3% including IOBS and 3.1% excluding IOBS. The most common microorganism isolated from autologous blood was coagulase-negative Staphylococci in 12 of 18 culture-positive units (66.7%). Alpha Streptococcus uiridans was isolated in 2 units (11%) and Staphylococcus aureus was isolated in 1 unit (5.5%). However, none of the patients who received the culture-positive autotransfusion blood showed clinical signs or laboratory findings of bacteremia. Safe ATDP is threatened by bacterial contamination that can be introduced by numerous sources, such as the donors' blood, the skin at the site of venipuncture, the environment and the phlebotomist's finger. In the cases of IOBS, protection against bacterial contamination at the surgical site is crucial. Here we discuss the relevance of our findings to the efforts to minimize the risks of contamination associated with autologous blood transfusion; risks that must be communicated to the patient in the process of informed consent. Continued research is required to identify the safest method of autologous blood transfusion.

[Pseudomonas bacteremia developing after whirlpool bath]. / Pseudomonas-bakteriaemi opstået efter anvendelse af Spa-bad.

Whirlpools may be responsible for transmission of microbial infections among the bathers if the technical hygienic conditions in the care of the bath are not observed. Two cases of infection with Pneudomonas bacteria were observed after use of whirlpools in a deluxe summer chalet. On the basis of the documented cases, the necessity for specific requirements concerning the installation, running and control of whirlpools used commercially should be considered. In their advisory brochures, the responsible authorities should ensure that the requirements made concerning whirlpools should be intensified so that these baths in summer chalets which are rented out should be subject to public control. Owners and users of whirlpools should be aware of the importance of meticulous hygiene in their care.