Association of hospital contact precaution policies with emergency department admission time.

BACKGROUND: Contact precautions are a widely accepted strategy to reduce in-hospital transmission of meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). However, these practices may have unintended deleterious effects on patients. AIM: To evaluate the effect of a modification in hospital-wide contact precaution practices on emergency department (ED) admission times. METHODS: During the study period, the hospital changed its contact precaution policy from requiring contact precautions for all patients with a history of MRSA or VRE to only those who presented with clinical conditions likely to contaminate the environment with pathogens. An interrupted time series analysis of ED admission times for adults for one year preceding and one year following this change was performed at a two-campus hospital. The main outcome was admission time, defined as time from decision to admit to arrival in an inpatient bed, for patients with MRSA or VRE compared with all other patients. The in-hospital MRSA and VRE acquisition rates were evaluated over the same period and have been published previously. FINDINGS: At one campus, admission time decreased immediately by 161min for MRSA patients (P=0.008) and 135min for VRE patients (P=0.003), and both continued to decrease over the duration of the study. There was no significant change in admission time at the second campus. CONCLUSIONS: Modifying contact precaution requirements for MRSA and VRE may be associated with improved ED admission time without significantly altering in-hospital MRSA and VRE acquisition.

Impact of contact precautions on falls, pressure ulcers and transmission of MRSA and VRE in hospitalized patients.

BACKGROUND: Hospitals use contact precautions to prevent the spread of meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). There is concern that contact precautions may have adverse effects on the safety of isolated patients. In November 2010, the infection control policy at an academic medical centre was modified, and contact precautions were discontinued for patients colonized or infected with MRSA or VRE (MRSA/VRE patients). AIM: To assess the rates of falls and pressure ulcers among MRSA/VRE patients and other adult medical-surgical patients, as well as changes in MRSA and VRE transmission before and after the policy change. METHODS: A single-centre retrospective hospital-wide cohort study was performed from 1st November 2009 to 31st October 2011. FINDINGS: Rates of falls and pressure ulcers were significantly higher among MRSA/VRE patients compared with other adult medical-surgical patients before the policy change (falls: 4.57 vs 2.04 per 1000 patient-days, P < 0.0001; pressure ulcers: 4.87 vs 1.22 per 1000 patient-days, P < 0.0001) and after the policy change (falls: 4.82 vs 2.10 per 1000 patient-days, P < 0.0001; pressure ulcers: 4.17 vs 1.19 per 1000 patient-days, P < 0.0001). No significant differences in the rates of falls and pressure ulcers among MRSA/VRE patients were found after the policy change compared with before the policy change. There was no overall change in MRSA or VRE hospital-acquired transmission. CONCLUSION: MRSA/VRE patients had higher rates of falls and pressure ulcers compared with other adult medical-surgical patients. Rates were not affected by removal of contact precautions, suggesting that other factors contribute to these complications. Further research is required among this population to prevent complications.

In vitro antimicrobial activities of novel anilinouracils which selectively inhibit DNA polymerase III of gram-positive bacteria.

The 6-anilinouracils are novel dGTP analogs that selectively inhibit the replication-specific DNA polymerase III of gram-positive eubacteria. Two specific derivatives, IMAU (6-[3'-iodo-4'-methylanilino]uracil) and EMAU (6-[3'-ethyl-4'-methylanilino]uracil), were substituted with either a hydroxybutyl (HB) or a methoxybutyl (MB) group at their N3 positions to produce four agents: HB-EMAU, MB-EMAU, HB-IMAU, and MB-IMAU. These four new agents inhibited Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus faecium. Time-kill assays and broth dilution testing confirmed bactericidal activity. These anilinouracil derivatives represent a novel class of antimicrobials with promising activities against gram-positive bacteria that are resistant to currently available agents, validating replication-specific DNA polymerase III as a new target for antimicrobial development.

Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy.

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.

Statistical evaluation of the role of Helicobacter pylori in stress gastritis: applications of splines and bootstrapping to the logistic model.

Stress gastritis is a serious problem in the intensive care unit population. The recent discovery of the causal nature of Helicobacter pylori (H. pylori) in the development of gastric ulcers led us to examine its relationship with stress gastritis. We investigated this relationship in 874 veterans admitted to intensive care units who were tested for the presence of H. pylori and followed for 6 weeks for the development of stress gastritis. We fit spline models to assess functional relationships and used the logistic model to determine the association between H. pylori and stress gastritis. The predictive ability of the model was assessed with receiver operating characteristic (ROC) curve analysis and validated with the bootstrapping technique. Increased anti-H. pylori immunoglobulin A concentrations were found to be an important predictor of stress gastritis independent of other known risk factors.

Risk factors for upper gastrointestinal bleeding in intensive care unit patients: role of helicobacter pylori. Federal Hyperimmune Immunoglobulin Therapy Study Group.

OBJECTIVE: To determine the role of preexisting Helicobacter pylori infection in the development of acute upper gastrointestinal (GI) hemorrhage in intensive care unit (ICU) patients in relation to other potential predisposing risk factors. DESIGN: Prospective, multicenter, cohort study. SETTING: Medical and surgical ICUs in six tertiary care Department of Veterans Affairs Medical Centers. PATIENTS: Eight-hundred seventy-four patients without previous GI bleeding or peptic ulcer disease who were enrolled in a multicenter, randomized, controlled trial of prophylactic intravenous immunoglobulin to prevent ICU-associated infections. INTERVENTIONS: This substudy of the larger intravenous immunoglobulin study only involved data analysis and had no intervention. All patients were enrolled in the larger study where they received intravenous immunoglobulin or placebo as intervention. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively evaluated for the development of acute upper GI hemorrhage while in an ICU. Anti-H. pylori immunoglobulin G and immnoglobulin A concentrations were determined by enzyme immunoassay on preintervention serum samples. Seventy-six (9%) patients had over upper GI bleeding and a mortality rate of 49%, as compared with a 15% mortality rate in patients who did not bleed (p < .001). By logistic regression analysis, the following factors were associated with an increased risk of bleeding: acute hepatic failure, prolonged duration of nasogastric tube placement, alcoholism, and an increased serum concentration of anti-H. pylori immunoglobulin A. CONCLUSIONS: Increased anti-H. pylori immunoglobulin A concentrations, prolonged nasogastric intubation, alcoholism, and acute hepatic failure were found to be independently correlated with the development of acute GI bleeding in an ICU setting. These observations should be prospectively confirmed in an independent population before being used for treatment guidelines.

Immunoprophylaxis against klebsiella and pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group.

To determine if passive immunization could decrease the incidence or severity of Klebsiella and Pseudomonas aeruginosa infections, patients admitted to intensive care units of 16 Department of Veterans Affairs and Department of Defense hospitals were randomized to receive either 100 mg/kg intravenous hyperimmune globulin (IVIG), derived from donors immunized with a 24-valent Klebsiella capsular polysaccharide plus an 8-valent P. aeruginosa O-polysaccharide-toxin A conjugate vaccine, or an albumin placebo. The overall incidence and severity of vaccine-specific Klebsiella plus Pseudomonas infections were not significantly different between the groups receiving albumin and IVIG. There was some evidence that IVIG may decrease the incidence (2.7% albumin vs. 1.2% IVIG) and severity (1.0% vs. 0.3%) of vaccine-specific Klebsiella infections, but these reductions were not statistically significant. The trial was stopped because it was statistically unlikely that IVIG would be protective against Pseudomonas infections at the dosage being used. Patients receiving IVIG had more adverse reactions (14.4% vs. 9.2%).

The effects of lactoferrin on gram-negative bacteria.

Lactoferrin is an iron-binding protein found in human mucosal secretions as well as the specific granules of polymorphonuclear leukocytes. A variety of functions have been ascribed to the protein, and it appears to contribute to antimicrobial host defense. In particular, it has been shown to have direct effects on pathogenic microorganisms including bacteriostasis and the induction of microbial iron uptake systems. Still its overall physiologic role remains to be defined. It has appeared logical that antimicrobial activity of the protein arises from sequestration of environmental iron thereby causing nutritional deprivation in susceptible organisms. This argument is buttressed by the finding that selected highly virulent pathogens have evolved techniques to subvert this effect and use the protein as an iron source. However, recent observations indicate that the protein has additional properties that contribute to host defense. Work by several groups has shown that the protein synergistically interacts with immunoglobins, complement, and neutrophil cationic proteins against Gram-negative bacteria. Further, both the whole protein and a cationic N-terminus peptide fragment directly damage the outer membrane of Gram-negative bacteria suggesting a mechanism for the supplemental effects. This review will summarize these diverse observations with a consideration of how the in vitro work relates to the physiological role of the protein.

Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment.

Although the antimicrobial activity of lactoferrin has been well described, its mechanism of action has been poorly characterized. Recent work has indicated that in addition to binding iron, human lactoferrin damages the outer membrane of gram-negative bacteria. In this study, we determined whether bovine lactoferrin and a pepsin-derived bovine lactoferrin peptide (lactoferricin) fragment have similar activities. We found that both 20 microM bovine lactoferrin and 20 microM lactoferricin release intrinsically labeled [3H]lipopolysaccharide ([3H]LPS) from three bacterial strains, Escherichia coli CL99 1-2, Salmonella typhimurium SL696, and Salmonella montevideo SL5222. Under most conditions, more LPS is released by the peptide fragment than by whole bovine lactoferrin. In the presence of either lactoferrin or lactoferricin there is increased killing of E. coli CL99 1-2 by lysozyme. Like human lactoferrin, bovine lactoferrin and lactoferricin have the ability to bind to free intrinsically labeled [3H]LPS molecules. In addition to these effects, whereas bovine lactoferrin was at most bacteriostatic, lactoferricin demonstrated consistent bactericidal activity against gram-negative bacteria. This bactericidal effect is modulated by the cations Ca2+, Mg2+, and Fe3+ but is independent of the osmolarity of the medium. Transmission electron microscopy of bacterial cells exposed to lactoferricin show the immediate development of electron-dense "membrane blisters." These experiments offer evidence that bovine lactoferrin and lactoferricin damage the outer membrane of gram-negative bacteria. Moreover, the peptide fragment lactoferricin has direct bactericidal activity. As lactoferrin is exposed to proteolytic factors in vivo which could cleave the lactoferricin fragment, the effects of this peptide are of both mechanistic and physiologic relevance.

Killing of gram-negative bacteria by lactoferrin and lysozyme.

Although lactoferrin has antimicrobial activity, its mechanism of action is not full defined. Recently we have shown that the protein alters the Gram-negative outer membrane. As this membrane protects Gram-negative cells from lysozyme, we have studied whether lactoferrin's membrane effect could enhance the antibacterial activity of lysozyme. We have found that while each protein alone is bacteriostatic, together they can be bactericidal for strains of V. cholerae, S. typhimurium, and E. coli. The bactericidal effect is dose dependent, blocked by iron saturation of lactoferrin, and inhibited by high calcium levels, although lactoferrin does not chelate calcium. Using differing media, the effect of lactoferrin and lysozyme can be partially or completely inhibited; the degree of inhibition correlating with media osmolarity. Transmission electron microscopy shows that E. coli cells exposed to lactoferrin and lysozyme at 40 mOsm become enlarged and hypodense, suggesting killing through osmotic damage. Dialysis chamber studies indicate that bacterial killing requires direct contact with lactoferrin, and work with purified LPS suggests that this relates to direct LPS-binding by the protein. As lactoferrin and lysozyme are present together in high levels in mucosal secretions and neutrophil granules, it is probable that their interaction contributes to host defense.

Identification, purification, and characterization of major antigenic proteins of Campylobacter jejuni.

Evidence from developing countries and volunteer studies indicates that immunity to Campylobacter jejuni and Campylobacter coli may be acquired, but the antigenic basis for this protection is poorly defined. We have purified to homogeneity four proteins with molecular weights of 28,000 (PEB1), 29,000 (PEB2), 30,000 (PEB3), and 31,000 (PEB4) from epidemic C. jejuni strain 81-176 using acid extraction and sequential ion-exchange, hydrophobic interaction, and gel filtration chromatography. The relative amino acid compositions of these four proteins are similar. NH2-terminal sequence analysis indicates that all four proteins are different, although the first 35 amino acids of PEB2 and PEB3 are 51.4% homologous. Isoelectric focusing showed that all four are basic proteins with pI of 8.5 for PEB1 protein and greater than 9.3 for the others. Use of the purified proteins as antigens in an IgG enzyme-linked immunosorbent assay (ELISA) found that seroconversion to the PEB1 or PEB3 proteins occurred in 15 of 19 patients with sporadic C. jejuni or C. coli infection. In comparison, only two, six, and 14 of these patients seroconverted to PEB2, PEB4, or the acid extract antigen. In an ELISA with whole bacterial cells as antigens, antiserum to the acid-extracted antigens showed broad recognition of C. jejuni, C. coli, C. fetus, C. lari, and Helicobacter pylori. Antiserum to PEB1 recognized all 35 C. jejuni and all 15 C. coli strains but none of the isolates of the other three bacterial species. The PEB1 and PEB3 proteins appear to be candidate antigens for both a Campylobacter vaccine and for serological assays for the pathogen.

Bacteremia in granulocytopenic patients in a tertiary-care general hospital.

Episodes of bacteremia in granulocytopenic patients during 1985 and 1986 at a tertiary-care general hospital were reviewed to assess the adequacy of current empiric antimicrobial therapy. The major pathogens in these cases were Pseudomonas aeruginosa, Enterobacteriaceae organisms, and Staphylococcus epidermidis. This combination of pathogens differed from that found at the same facility from 1975 to 1977, when Staphylococcus aureus and streptococci predominated. When apparent, the sources of infection were predominantly venous catheters, the lower respiratory tract, and the urinary tract; most frequently there was no identifiable focus. S. epidermidis and streptococci were isolated more frequently during initial episodes of febrile bacteremia, and P. aeruginosa was isolated more often during subsequent episodes. If a narrow definition for therapeutic outcome is used, only 38% of episodes had a favorable response; response rates were no different with appropriate or inappropriate therapy. The low response rate may have been related to the use of data from the previous review to guide empiric therapy and to the subsequent inadequate treatment of infections caused by Pseudomonas and Enterobacter organisms. The overall mortality per total bacteremic episodes was 19%, and the primary factor associated with mortality was pneumonia (P less than .0001). This study emphasizes the need for ongoing surveillance of local patterns of bacteremia to direct empiric therapy.

Detection of Listeria monocytogenes by using the polymerase chain reaction.

A method was developed for detection of Listeria monocytogenes by polymerase chain reaction amplification followed by agarose gel electrophoresis or dot blot analysis with a 32P-labeled internal probe. The technique identified 95 of 95 L. monocytogenes strains, 0 of 12 Listeria strains of other species, and 0 of 12 non-Listeria strains.