A simplified blood culture sampling protocol for reducing contamination and costs: a randomized controlled trial.

OBJECTIVES: Blood culture contamination carries risks for patients, such as unnecessary antimicrobial therapy and other additional hazards and costs. One method shown to be effective in reducing contamination is initial blood specimen diversion during collection. We hypothesized that initial blood specimen diversion without a designated device or procedure would suffice for reduction in blood culture contamination rate. METHODS: From 1 September 2017 through to 6 September 2018, we conducted a randomized controlled trial to assess the effect of an initial-specimen diversion technique (ISDT) on the rate of blood-culture contamination by changing the order of sampling using regular vacuum specimen tubes instead of commercially available sterile diversion devices. We included adults from whom the treating physician planned to take blood cultures and additional blood chemistry tests. Additionally, we evaluated the potential economic benefits of an ISDT. This was a researcher-initiated trial, Clinicaltrials.gov NCT03088865. RESULTS: In all, 756 patients were enrolled. This method, compared with the standard procedure in use at our medical centre, reduced contamination by 66% (95% CI 17%-86%), from 20/400 (5%) with the standard method to 6/356 (1.6%) with the ISDT, without compromising detection of true bloodstream infection and at no additional cost. Hospital-wide implementation of ISDT was associated with a 1.1% saving in hospitalization days. CONCLUSIONS: We offer this novel approach as a simple, cost-effective measure to reduce risks to patient safety from contaminated blood cultures, without the need for using costly devices.

Epidemiology of infective endocarditis in a tertiary-center in Jerusalem: a 3-year prospective survey.

BACKGROUND: Epidemiological features of infective endocarditis have changed during the last decades because of increases in the prevalence of health care exposure and of Staphylococcus aureus bloodstream infection. Consequently, the role of surgery is evolving. We aim to provide a contemporary profile of epidemiological, microbiological, and clinical features of infective endocarditis in a tertiary medical center, and identify predictors of mortality. METHODS: A prospective observational cohort study of consecutive adult patients with definite endocarditis according to the modified Duke criteria. Data were collected from January 1, 2009 through October 31, 2011 following a predefined case report form designed by the ICE-PCS. RESULTS: Among 70 endocarditis episodes, 25.7% involved prosthetic valves and 11.5% were device related. Forty-four percent of episodes were health-care associated. The predominant causative microorganism on native valve, prosthetic valve and device related endocarditis was Staphylococcus aureus (33.3%). Viridans group streptococci accounted for the majority of community-acquired endocarditis (36.1%). At least one complication occurred in 50% of the episodes. One third of the patients who had an indication for surgery were operated upon. Six month case fatality ratio was 40%. Sixty-five percent of patients with a contraindication to surgery died, compared with 9% and 28.5% who were treated surgically and medically, respectively. In multivariable analysis, age was a predictor of mortality. CONCLUSION: Compared with other series, we observed more health-care associated endocarditis, and a higher mortality. Nearly half of all deaths were in patients who had a contraindication to surgery. Careful evaluation of contraindications to surgery is warranted.

Repeat endocarditis: analysis of risk factors based on the International Collaboration on Endocarditis - Prospective Cohort Study.

Repeat episodes of infective endocarditis (IE) can occur in patients who survive an initial episode. We analysed risk factors and 1-year mortality of patients with repeat IE. We considered 1874 patients enrolled in the International Collaboration on Endocarditis - Prospective Cohort Study between January 2000 and December 2006 (ICE-PCS) who had definite native or prosthetic valve IE and 1-year follow-up. Multivariable analysis was used to determine risk factors for repeat IE and 1-year mortality. Of 1874 patients, 1783 (95.2%) had single-episode IE and 91 (4.8%) had repeat IE: 74/91 (81%) with new infection and 17/91 (19%) with presumed relapse. On bivariate analysis, repeat IE was associated with haemodialysis (p 0.002), HIV (p 0.009), injection drug use (IDU) (p < 0.001), Staphylococcus aureus IE (p 0.003), healthcare acquisition (p 0.006) and previous IE before ICE enrolment (p 0.001). On adjusted analysis, independent risk factors were haemodialysis (OR, 2.5; 95% CI, 1.2-5.3), IDU (OR, 2.9; 95% CI, 1.6-5.4), previous IE (OR, 2.8; 95% CI, 1.5-5.1) and living in the North American region (OR, 1.9; 95% CI, 1.1-3.4). Patients with repeat IE had higher 1-year mortality than those with single-episode IE (p 0.003). Repeat IE is associated with IDU, previous IE and haemodialysis. Clinicians should be aware of these risk factors in order to recognize patients who are at risk of repeat IE.

Colistin is relatively safe in hematological malignancies and hematopoietic stem cell transplantation patients.

PURPOSE: Colistin is increasingly used as the last-resort treatment option against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, but its nephrotoxicity is of concern, especially in severely ill patients. The aim of this study was to analyze the toxicity of colistin therapy in adults and children with hematological malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients. METHODS: Data on HSCT recipients and HM patients, treated with intravenous colistin (2.5-5 mg/kg/day in children and 3-6 million international units (IU) in adults, adjusted to renal function) during the period 2008-2011 in our center, were retrospectively collected and analyzed. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease). RESULTS: Twenty-nine children and adults received 38 courses of intravenous colistin (2.5-5 mg/kg/day in children and 3-6 × 10(6) IU in adults, adjusted to renal function) [allogeneic HSCT (22 courses) and HM (16 courses)] for 3-28 days (median 10 days) for empirical therapy for nosocomial clinical sepsis (28) or local infection (6), and bacteremia with MDR Gram-negative rods (4). Nephrotoxicity was observed at the end of 4 (10.5%) courses. In 32 (84%) courses, nephrotoxic medications were concomitantly administered. Two patients had convulsions, probably unrelated to colistin. Seven patients (18%) died while on colistin therapy. No death was attributed to an adverse effect of colistin. CONCLUSIONS: Treatment with intravenous colistin, with dosage adjusted to renal function, was relatively safe for HM/HSCT patients, even with concomitantly administered nephrotoxic medications. Concern about nephrotoxicity should not justify a delay in initiating empirical colistin treatment in situations where infection with MDR Gram-negative rods is likely.

qnr prevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States.

We screened 313 ceftazidime-resistant Enterobacteriaceae isolates obtained in the United States from 1999 to 2004 for all three known qnr genes. A qnr gene was present in 20% of Klebsiella pneumoniae isolates, 31% of Enterobacter sp. isolates, and 4% of Escherichia coli isolates. qnrA and qnrB occurred with equivalent frequencies and, except for qnrB in enterobacters, were stable over time. qnrS was absent.

Case clustering in infective endocarditis: the role of availability bias.

Limited data exist regarding the impact of variations in clinical practice and physicians' cognitive bias on the diagnosis of infective endocarditis (IE). As an illustration of these effects, unexpected clustering of IE diagnosis was encountered in a prospectively studied cohort. Transoesophageal echocardiography examinations for suspected IE were performed more frequently following a diagnosis of IE, and were associated with a subsequent cluster of IE cases. The cognitive bias of physicians resulting from a recent case of IE can lead to a transient increase in diagnosing additional cases of IE.

Broader distribution of plasmid-mediated quinolone resistance in the United States.

The plasmid-encoded quinolone resistance gene qnrA confers low-level quinolone resistance, facilitating selection of higher-level resistance. Epidemiologic surveys for qnrA were extended to isolates of Enterobacter spp. and to quinolone-susceptible Enterobacteriaceae. Two (10%) of 20 ceftazidime-resistant quinolone-susceptible Klebsiella pneumoniae strains carried the gene, as did 12 (17%) of 71 ceftazidime-resistant Enterobacter strains from across the United States. One of these Enterobacter isolates was quinolone susceptible. Thus, qnrA is present in quinolone-resistant and quinolone-susceptible Enterobacter and Klebsiella strains in the United States.

MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus.

In an analysis of the resistance mechanisms of an mgrA mutant, we identified two genes encoding previously undescribed transporters, NorB and Tet38. norB was 1,392 bp and encoded a predicted 49-kDa protein. When overexpressed, NorB led to an increase in resistance to hydrophilic quinolones, ethidium bromide, and cetrimide and also to sparfloxacin, moxifloxacin, and tetracycline, a resistance phenotype of the mgrA mutant. NorA and NorB shared 30% similarity, and NorB shared 30 and 41% similarities with the Bmr and Blt transporters of Bacillus subtilis, respectively. The second efflux pump was a more selective transporter that we have called Tet38, which had 46% similarity with the plasmid-encoded TetK efflux transporter of S. aureus. tet38 was 1,353 bp and encoded a predicted 49-kDa protein. Overexpression of tet38 produced resistance to tetracycline but not to minocycline and other drugs. norB and tet38 transcription was negatively regulated by MgrA. Limited binding of MgrA to the promoter regions of norB and tet38 was demonstrated by gel shift assays, suggesting that MgrA was an indirect regulator of norB and tet38 expression. The mgrA norB double mutant was reproducibly twofold more susceptible to the tested quinolones than the mgrA mutant. The mgrA tet38 double mutant became more susceptible to tetracycline than the wild-type parent strain. These data demonstrate that overexpression of NorB and Tet38 contribute, respectively, to the hydrophobic quinolone resistance and the tetracycline resistance of the mgrA mutant and that MgrA regulates expression of norB and tet38 in addition to its role in regulation of norA expression.

Bacteroides fragilis vertebral osteomyelitis secondary to anal dilatation.

STUDY DESIGN: A case report of anaerobic vertebral osteomyelitis after anal dilatation. OBJECTIVES: To present a patient with monomicrobial anaerobic vertebral osteomyelitis secondary to a previously undescribed source of infection. SUMMARY OF BACKGROUND DATA: A 17-year-old boy presented with low back pain 3 months after anal dilatation. METHODS: Physical examination, technetium-99m bone scan, plain radiograph, CT, and MRI studies of the lumbar spine were used to clinically diagnose lumbar osteomyelitis. Culture material from the involved disc was positive for Bacteroides fragilis. RESULTS: The patient recovered after 8 weeks of treatment with oral metronidazole. CONCLUSIONS: Bacteroides fragilis hematogenous osteomyelitis is a rare entity. This is the first reported case of such disease after anal dilatation.

Vascular access via peripherally inserted central venous catheters (PICCs): experience in 40 patients with acute myeloid leukemia at a single institute.

Reliable long-term vascular access is essential for the treatment of patients with acute myeloid leukemia (AML). Although peripherally inserted central catheters (PICCs) have been in use for many years, little data exist on their use in patients receiving intensive chemotherapy. We retrospectively reviewed all AML patients who had a PICC inserted between July 95 and May 98. Fifty two PICCs were inserted in 40 patients with AML. Thirty three PICCs were inserted during severe thrombocytopenia (platelets < 50 x 10(9)/L), and 31 during severe neutropenia (neutrophils < 0.5 x 10(9)/L). Mean catheter duration was 82 (median 63, range 3-441) days for a total of 4274 catheter days. A mean of 1.8 chemotherapy courses were administered via each PICC. There were 5 early complications of PICC placement. Other mechanical complications occurred in 14 catheters and phlebitis in 12. Twenty blood stream infections (BSI) occurred in 17 patients. All BSIs occurred during neutropenia. Seventeen PICCs were removed due to the following complications - phlebitis (11), possible catheter related BSI (4), mechanical reasons in 3 (2 with concomitant phlebitis) and persistent fever (1). PICC duration was significantly shorter in these 17 catheters (52.9 v 96.4 days in the other 35, p=0.0289). We conclude that PICCs provide long-term vascular access with an acceptable complication rate in patients with AML. However, a randomised trial is required before PICCs can be considered an alternative to tunneled central venous catheters in these patients.

Pulmonary leukostasis: role of perfusion lung scan in diagnosis and follow up.

A patient with hyperleukocytic myelomonocytic leukemia who presented to the emergency room with sudden pleuritic chest pain and dyspnea is reported. Clinical manifestations included dyspnea tachypnea and hyperventilation. Blood gas analysis revealed hypoxemia, hypocarbia, and respiratory alkalosis. Chest X ray was normal, and perfusion lung scan revealed a diffuse vascular occlusive pattern compatible with pulmonary leukostasis. The patient underwent immediate leukapheresis with subsequent mitigation of symptoms. A second perfusion lung scan showed evidence of significant improvement. To our knowledge this is the first published case of hyperleukocytosis presenting with pulmonary leukostasis that was successfully diagnosed and followed by serial perfusion lung scan.

Recovery of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Israel.

Candida dubliniensis is a recently discovered yeast species principally associated with carriage and disease in the oral cavities of human immunodeficiency virus (HIV)-infected individuals. To date the majority of isolates of this species have been identified in Europe and North America. In this study, five Candida isolates recovered from separate HIV-negative hospitalized patients in Jerusalem, Israel, were presumptively identified as C. dubliniensis on the basis of their dark green coloration when grown on CHROMagar Candida medium. Their identification was confirmed by a variety of techniques, including carbohydrate assimilation profiles, absence of growth at 45 degrees C, positive reaction with C. dubliniensis-specific antibodies as determined by indirect immunofluorescence analysis, and positive amplification with C. dubliniensis-specific PCR primers. All five strains were shown to be susceptible to a range of antifungal agents, including fluconazole. One of the five isolates was recovered from urine specimens, while the remaining four were recovered from upper respiratory tract and oral samples. While none of the patients was HIV positive, all were receiving broad-spectrum antibacterials at the time isolates of C. dubliniensis were obtained from clinical specimens. This study describes the first isolates of C. dubliniensis from the Middle East and confirms that this yeast can be associated with carriage and infection in the absence of HIV infection.

Fluconazole in transplant recipients: options and limitations.

Fluconazole is currently a first-line agent used for therapy of non-critically ill patients with candidal infection. Its efficacy, the availability of an oral formula, and its relatively low toxicity make it a very attractive drug for use in many clinical situations. The advisability of prophylaxis and empirical treatment in transplant patients is a difficult issue for the following reasons: the potential emergence of resistance to the azoles, the lack of solid data establishing its advantage over placebo and/or oral nonabsorbable antifungal agents in some of the clinical conditions encountered, its ineffectiveness against molds, and its cost. Judicious use of fluconazole where its efficacy has been well established would provide the best therapy for patients and would limit the emergence of potential pathogens. As new antifungal agents are approved for clinical use, appropriate clinical trials will need to be designed and conducted in order for clinicians to make rational decisions in selecting the most appropriate drug for the specific indication. Prophylaxis and treatment with fluconazole in various transplant situations is reviewed.

Predicting postinfarction left ventricular dysfunction based on the configuration of the QRS complex and ST segment in the initial ECG of patients with a first anterior wall myocardial infarction.

The objective of the study was to identify patients with anterior wall acute myocardial infarction (AMI) at high risk of postinfarction left ventricular dysfunction (LVD). This study population included all patients admitted with a diagnosis of anterior wall AMI (ST segment elevation of > 1 mm in 2 or more precordial leads) without history or ECG evidence of antecedent AMI,who underwent assessment of left ventricular ejection fraction (LVEF) during emergency hospitalization. ST segment deviation from baseline was measured manually 0.08 s after the J point in all leads. Patients (n = 81) were classified into two groups based on the configuration of the QRS complex and ST segment: ST > 1 mm with preserved (pattern A; n = 60) or distorted terminal QRS (emergence of the J point at a level above the lower half of the R wave or disappearance of the S wave in leads with an Rs configuration; pattern B; n = 21). LVD (LVEF < 40%) was significantly more prevalent in patients with pattern B than pattern A (48 vs. 12%; p = 0.002). There was no correlation between the number of leads with ST segment elevation and LVD (p = 0.47). The sum of ST segment elevation in involved leads correlated weakly, yet significantly with LVEF (R = -0.22; p < 0.05). In conclusion, patients with anterior wall AMI and pattern B in the initial ECG are at high risk of post-AMILVD.

Spectrum of antimicrobial activity and assembly of dermaseptin-b and its precursor form in phospholipid membranes.

Dermaseptins are 27-34 amino acid antimicrobial peptides that irreversibly inhibit growth of pathogenic filamentous fungi, in addition to their ability to inhibit the growth of bacteria, yeasts, and protozoa. Synthetic peptides, with sequences corresponding to dermaseptin-b (DS-b) and its N-terminal extended precursor form dermaseptin-B (DS-B), were synthesized and investigated with respect to their spectrum of antimicrobial activity and their mode of interaction with model membranes composed of PS or PC/PS phospholipids. We found that DS-B is much more potent than DS-b against all microorganisms tested. Furthermore, despite significant structural identity between DS-b and DS-S (Pouny et al., 1992), only the former is highly effective at inhibiting the growth of filamentous fungi. The peptides were labeled selectively at their N-terminal amino acid with either 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or rhodamine fluorescent probes, which facilitated the determination of their partition coefficients with phospholipid membranes and their organization in their membrane-bound state. The partition coefficients of DS-B are 10-fold higher than those of DS-b and DS-S, with both acidic and zwitterionic phospholipid vesicles. This may explain the ability of DS-B to permeate both types of vesicles efficiently. Furthermore, while both DS-b and DS-B interact with phospholipid membranes in a noncooperative manner, they are self-associated in their membrane-bound state. This noncooperative binding probably prevents aggregation of the peptides on the surface of outer bacterial membranes, and assists them in efficiently diffusing into the inner target membranes. The exceptional property of DS-B to bind strongly to phospholipid membranes and to form small bundles correlates with its high potential to kill yeast and filamentous fungi. As a molecular model, dermaseptins may be of potential interest in drug design, particularly in antifungal warfare.

Secondary structure and membrane localization of synthetic segments and a truncated form of the IsK (minK) protein.

IsK, also referred to as minK, is a membrane protein consisting of 130 amino acids and localized mainly in epithelial cells but also in human T lymphocytes. Depending on the cRNA concentration that was injected into Xenopus oocytes, IsK and its truncated forms can induce either a K+ current alone or both K+ and Cl- currents [Attali et al. (1993) Nature 365, 850-852]. To obtain information on the secondary structure and the topology of IsK in a membrane-bound state, the synthesis, fluorescent-labeling, and structural and functional characterization of five polypeptides of 20-63 amino acids within the rat IsK protein were examined. The alpha-helical content of the segments, assessed in methanol using circular dichroism, suggests that both the N-terminal and transmembrane segments of IsK adopt alpha-helical structures. Binding experiments and the blue shift of 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled peptides suggest that while both the alpha-helical transmembrane segment and the N-terminal of IsK are located within the lipid bilayer, the linking segment between the two segments lies on the surface of the membrane. The fluorescence energy transfer, between donor and acceptor-labeled truncated IsK, suggests that it aggregates within phospholipid membranes. Although a protein whose sequence is similar to that of truncated IsK can induce K+ channel activity when expressed in Xenopus oocytes, the inability of a truncated IsK to form functional K+ channels in planar lipid membranes supports increasing evidence that the protein alone cannot form a K+ channel.