Validity of surrogate endpoints assessing central venous catheter-related infection: evidence from individual- and study-level analyses.

OBJECTIVES: The prevention of catheter-related bloodstream infection (CRBSI) has been an area of intense research, but the heterogeneity of endpoints used to define catheter infection makes the interpretation of randomized controlled trials (RCTs) problematic. The aim of this study was to determine the validity of different endpoints for central venous catheter infections. DATA SOURCES: (a) Individual-catheter data were collected from 9428 catheters from four large RCTs; (b) study-level data from 70 RCTs were identified with a systematic search. Eligible studies were RCTs published between January 1987 and October 2018 investigating various interventions to reduce infections from short-term central venous catheters or short-term dialysis catheters. For each RCT the prevalence rates of CRBSI, quantitative catheter tip colonization, catheter-associated infection (CAI) and central line-associated bloodstream infection (CLABSI) were extracted for each randomized study arm. METHODS: CRBSI was used as the gold-standard endpoint, for which colonization, CAI and CLABSI were evaluated as surrogate endpoints. Surrogate validity was assessed as (1) the individual partial coefficient of determination (individual-pR2) using individual catheter data; (2) the coefficient of determination (study-R2) from mixed-effect models regressing the therapeutic effect size of the surrogates on the effect size of CRBSI, using study-level data. RESULTS: Colonization showed poor agreement with CRBSI at the individual-patient level (pR2 = 0.33 95% CI 0.28-0.38) and poor capture at the study level (R2 = 0.42, 95% CI 0.21-0.58). CAI showed good agreement with CRBSI at the individual-patient level (pR2 = 0.80, 95% CI 0.76-0.83) and moderate capture at the study level (R2 = 0.71, 95% CI 0.51-0.85). CLABSI showed poor agreement with CRBSI at the individual patient level (pR2 = 0.34, 95% CI 0.23-0.46) and poor capture at the study level (R2 = 0.28, 95% CI 0.07-0.76). CONCLUSIONS: CAI is a moderate to good surrogate endpoint for CRBSI. Colonization and CLABSI do not reliably reflect treatment effects on CRBSI and are consequently more suitable for surveillance than for clinical effectiveness research.

The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: a prospective study utilizing molecular subtyping.

To delineate the pathogenesis and epidemiology of catheter-related infection with Swan-Ganz pulmonary artery (PA) catheters, a prospective clinical study of hospitalized adult medical and surgical patients was done. Role of catheter material was assessed by randomizing insertions to heparin-bonded PA catheters made of polyvinylchloride or polyurethane. Sources of infection and pathogenesis were studied by culturing skin, the introducer, the PA catheter tip, all hubs, infusate from each lumen, and the extravascular portion of the PA catheter beneath the external protective plastic sleeve. Concordance between isolates from sources and infected catheters was determined by speciation, antibiogram, and for coagulase-negative staphylococci, plasmid profile analysis. Risk factors for infection were determined by stepwise logistic regression. Overall, 65 (22%) of 297 Swan-Ganz catheters showed local infection of the introducer (58 catheters) or the intravascular portion of the PA catheter (20 catheters); only two catheters (0.7%) caused bacteremia. Eighty percent of infected Swan-Ganz catheters (the introducer or PA catheter) showed concordance with organisms cultured from skin of the insertion site, 17% with a contaminated hub and 18% with organisms contaminating the extravascular portion of the PA catheter beneath the sleeve. Isolates from infected PA catheters were most likely to show concordance with concomitantly infected introducers (71%). Cutaneous colonization of the insertion site with greater than 10(2) cfu/10 cm2 (relative risk [RR] 5.5; p less than 0.001), insertion into an internal jugular vein (RR 4.3; p less than 0.01), catheterization greater than 3 days (RR 3.1; p less than 0.01), and insertion in the operating room using less stringent barrier precautions (RR 2.1; p = 0.03) were each associated with a significantly increased risk of catheter-related infection. The risk of bacteremic infection with Swan-Ganz catheters is now low, in the range of 1%, with reasonable care. Swan-Ganz catheters are vulnerable to contamination from multiple sources, but the patient's skin is the single most important source of organisms causing invasive infection, which in most cases involves the introducer rather than the PA catheter. Heavy colonization of the insertion site, percutaneous insertion in the internal jugular vein rather than subclavian vein, catheterization longer than 3 days, and insertion with less stringent barrier precautions significantly increase the risk of catheter-related infection. These findings hold promise for application to management of Swan-Ganz catheters and research in catheter design to reduce the risk of catheter-related infection.

Acute psychosis in a patient receiving trimethoprim-sulfamethoxazole intravenously.

A 55-year-old man became acutely psychotic and had a pseudoseizure after receiving six doses of intravenously administered trimethoprim-sulfamethoxazole. These symptoms resolved within 24 hours after discontinuation of the medication; this finding suggests a causal effect of the drug administration.

A pseudo-epidemic involving bone allografts.

Preimplantation cultures of four sterile bone allograft specimens grew Comomonas acidovorans and Pseudomonas species. An epidemiological investigation, including molecular subtyping methods, revealed that the allograft specimens were contaminated in a microbiology laboratory sonicator water bath.

Association of Legionnaires' disease with construction: contamination of potable water?

OBJECTIVE: To describe two cases of nosocomial legionellosis and discuss the epidemiology of this infection. DESIGN: Potable water was collected from multiple sites. Patient and environmental isolates were characterized by the Legionella slide agglutination test and monoclonal antibody subtyping. Concordance among isolates was confirmed by pulsed-field gel electrophoresis (PFGE). SETTING: A 713-bed university-affiliated hospital. RESULTS: There was widespread contamination of potable water with Legionella pneumophila during a period of major construction; cooling towers were without growth of Legionella. One patient's isolate was the same by PFGE as the environmental isolate collected from the water faucet in his room. Control measures included superheating water used in all patient care areas to 75 degrees C for 72 hours and flushing superheated water through faucets and showers; cleaning shower heads with a sonicator washer; and raising the hot water storage tank temperature from 43 degrees C to 52 degrees C. After these interventions, repeat environmental cultures over the next 6 months were without growth of Legionella, and no further cases of nosocomial legionnaires' disease were documented. An association between legionnaires' disease and construction is postulated. Heightened surveillance and preventive measures may be warranted during periods of excavation on hospital grounds or when potable water supplies are otherwise shut down and later repressurized.

Controlling vancomycin-resistant enterococci.

After controlling an epidemic of vanB-type vancomycin-resistant Enterococcus faecium (VRE), we contained a subsequent vanA E faecium outbreak by using prospective laboratory-based surveillance, placing patients with VRE in private rooms, requiring the use of both gowns and gloves by all personnel entering the patients' rooms, and conducting prevalence surveys of patients on affected wards.

Surgical management of necrotizing Candida esophagitis.

Invasive esophageal candidiasis produced transmural necrosis leading to perforation in 2 patients aged 10 and 27 years. Both patients survived after esophageal resection and complete diversion. One patient with acute leukemia and neutropenia experienced systemic candidiasis, which resolved after esophagectomy. Esophagectomy and diversion for yeast-induced necrosis may lead to complete recovery and resolution of disseminated candidiasis when combined with systemic antifungal therapy.

Bacteriology, safety and prevention of infection associated with continuous intravenous infusions.

There are over 50,000 intravascular catheter-associated bloodstream infections in the United States each year; globally, the number of these infections is likely to be much higher. At least half of these bloodstream infections are caused by staphylococci. The source of most pathogens causing endemic catheter-associated bloodstream infections is the catheter insertion site or the catheter hub, whereby microbes migrate into the bloodstream along the outside or inside of the catheter, respectively. The pathogenesis of epidemic intravascular catheter-related bloodstream infections is quite different. Epidemic bloodstream infections are due to manufacturer-related contamination or contamination that occurs at the location of catheter use, such as the hospital. These epidemics have most often been traced to contamination of intravenous solutions such as hyperalimentation or medications, blood products, contaminated cutaneous antiseptics or faulty decontamination of reusable devices. The prevention of infection associated with continuous intravenous infusion of factor VIII poses a number of challenges. Assurances of the sterility of the product is of paramount importance, as is proper storage of the product prior to use. Prevention of infection will further require particular attention to the conditions surrounding insertion of the catheter, including the optimal site of insertion, maximal barrier precautions and optimal disinfection of the insertion sites, and also to conditions surrounding maintenance of the device after insertion, including proper disinfection and aseptic techniques when manipulating the catheter hub, daily assessment of the insertion site, and maintaining scheduled changes of the intravenous tubing. With proper precautions, the risk of serious infection associated with a continuous infusion of factor VIII should be minimal.

Defining intravascular catheter-related infections: a plea for uniformity.

This article defines the complex interaction between catheterized patients and invading microbial pathogens. Catheter colonization reflects significant growth of a microbe on a catheter component. Localized intravascular catheter-related infection denotes infection at the exit site, tunnel tract, or pocket, in the absence of bloodstream infection. Systemic intravascular catheter-related infection is a complication of colonization or localized infection, usually documented by invasion of the bloodstream. Catheter sepsis is a systemic infection that is difficult to define because symptoms associated with bloodstream infection caused by the most common pathogens to infect catheterized patients, coagulase-negative staphylococci, may not meet the previously published criteria of sepsis. It is hoped that the information contained here will lead to greater uniformity in the definitions used by the many investigators in this fascinating field.

Leptospirosis in an urban setting: case report and review of an emerging infectious disease.

Leptospiosis is a common zoonosis affecting most mammals. Leptospirosis has protean manifestations ranging from a flu-like illness to fulminant hepatic and renal failure culminating in death. Although the diagnosis is often not considered upon presentation, the literature suggests that leptospirosis is a reemerging infectious disease in urban centers throughout the industrialized world. It will be incumbent upon Emergency Physicians to include this spirochetal disease in the differential diagnosis of febrile patients with appropriate risk factors and symptomatology. We present the case of a 36 year-old woman who presented to the Emergency Department with fever and hypotension. We review the literature on leptospirosis with specific focus on risk factors and pathogenesis, clinical manifestations, diagnosis, treatment, and outcome.

Oseltamivir-resistant 2009-2010 pandemic influenza A (H1N1) in an immunocompromised patient.

Although neuraminidase inhibitors are active against most 2009-2010 pandemic influenza A (H1N1) swine-origin strains, sporadic cases of oseltamivir resistance have been described. Since April 2009, 54 cases of oseltamivir-resistant H1N1 swine-origin have been reported in the USA (http://www.cdc.gov/flu/weekly/; accessed 1 February 2010). Approximately 1.4% of tested isolates are oseltamivir resistant. We report a patient with an underlying hematological malignancy who was hospitalized with influenza A (H1N1) swine-origin and whose strain developed oseltamivir resistance during therapy.

Quantitative analysis and molecular fingerprinting of methicillin-resistant Staphylococcus aureus nasal colonization in different patient populations: a prospective, multicenter study.

OBJECTIVES: To better understand the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in different patient populations, to perform quantitative analysis of MRSA in nasal cultures, and to characterize strains using molecular fingerprinting. DESIGN: Prospective, multicenter study. SETTING: Eleven different inpatient and outpatient healthcare facilities. PARTICIPANTS: MRSA-positive inpatients identified in an active surveillance program; inpatients and outpatients receiving hemodialysis; inpatients and outpatients with human immunodeficiency virus (HIV) infection; patients requiring cardiac surgery; and elderly patients requiring long-term care. METHODS. Nasal swab samples were obtained from January 23, 2006, through July 27, 2007; MRSA strains were quantified and characterized by molecular fingerprinting. RESULTS: A total of 444 nares swab specimens yielded MRSA (geometric mean quantity, 794 CFU per swab; range, 3-15,000,000 CFU per swab). MRSA prevalence was 20% for elderly residents of long-term care facilities (25 of 125 residents), 16% for HIV-infected outpatients (78 of 494 outpatients), 15% for outpatients receiving hemodialysis (31 of 208 outpatients), 14% for inpatients receiving hemodialysis (86 of 623 inpatients), 3% for HIV-infected inpatients (5 of 161 inpatients), and 3% for inpatients requiring cardiac surgery (6 of 199 inpatients). The highest geometric mean quantity of MRSA was for inpatients requiring cardiac surgery (11,500 CFU per swab). An association was found between HIV infection and colonization with the USA300 or USA500 strain of MRSA (P < or = .001). The Brazilian clone was found for the first time in the United States. Pulsed-field gel electrophoresis patterns for 11 isolates were not compatible with known USA types or clones. CONCLUSION: Nasal swab specimens positive for MRSA had a geometric mean quantity of 794 CFU per swab, with great diversity in the quantity of MRSA at this anatomic site. Outpatient populations at high risk for MRSA carriage were elderly residents of long-term care facilities, HIV-infected outpatients, and outpatients receiving hemodialysis.

Antimicrobial resistance of community-acquired bloodstream isolates of viridans group streptococci.

Infections due to antimicrobial-resistant viridans group streptococci are increasing. The present study was done to determine the frequency of antibiotic resistance among community-acquired viridans group streptococci isolated from blood cultures and to identify the risk factors associated with acquiring antibiotic-resistant viridans group streptococci. Twenty-eight community-acquired viridans group streptococcal isolates were recovered from 27 patients, of which 89%, 86%, 79%, 61%, and 39% were susceptible to ceftriaxone, clindamycin, tetracycline, penicillin, and erythromycin, respectively; 100% were susceptible to levofloxacin and vancomycin. Among the patients with previous antibiotic use, 73% had penicillin non-susceptible viridans group streptococci, compared with 18% who did not receive prior antibiotics (p = 0.006). Patients with and without prior antibiotic use, 27% and 0%, respectively, had ceftriaxone non-susceptible viridans group streptococci isolates, respectively (p = 0.05). Patients with and without prior antibiotic use, 45% and 6%, respectively, had tetracycline non-susceptible viridans group streptococci isolates, respectively (p = 0.02). No other risk factors for isolation of non-susceptible viridans group streptococci were identified.

Prevention of intravascular catheter-related infections.

PURPOSE: To review the literature on prevention of intravascular catheter-related infections. DATA SOURCES: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles. Primary authors were contacted directly if data were incomplete. STUDY SELECTION: Studies met the following criteria unless otherwise stated: Trials were prospective and randomized; catheters were inserted into new sites, not into old sites over guidewires; catheter cultures were done by using semi-quantitative or quantitative methods; and, for prospective studies, catheter-related bloodstream infection was confirmed by microbial growth from percutaneously drawn blood cultures that matched catheter cultures. DATA EXTRACTION: Data on population, methods, preventive strategy, and outcome (measured as catheter-related bloodstream infections) were gathered. The quality of the data was graded by using preestablished criteria. DATA SYNTHESIS: The recommended preventive strategies with the strongest supportive evidence are full barrier precautions during central venous catheter insertion; subcutaneous tunneling short-term catheters inserted in the internal jugular or femoral veins when catheters are not used for drawing blood; contamination shields for pulmonary artery catheters; povidone-iodine ointment applied to insertion sites of hemodialysis catheters; specialized nursing teams caring for patients with short-term peripheral venous catheters, especially at institutions with a high incidence of catheter-related infection; no routine replacement of central venous catheters; antiseptic chamberfilled hub or hub-protective antiseptic sponge for central venous catheters; and use of chlorhexidine-silver sulfadiazine-impregnated or minocycline-rifampin-impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies that do not incorporate antimicrobial agents (for example, maximal barrier precautions). CONCLUSIONS: Simple interventions can reduce the risk for serious catheter-related infection. Adequately powered randomized trials are needed.