Case-control study to identify factors associated with mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with increased mortality. Delay in appropriate antimicrobial therapy (DAAT) is an important risk factor for death, although confounding between carriage of MRSA and DAAT has not been resolved. We studied the association of risk factors with mortality and searched for specific populations vulnerable to DAAT. We conducted a case-control study comparing patients with MRSA bacteraemia who died during hospitalization (cases) with patients with MRSA bacteraemia who survived (controls) in three medical centres in two states. Patients were identified using computerized hospital databases for the years 2001-2005. Medical records were retrieved and various epidemiological data extracted. Bivariate and multivariate logistic regression analyses were performed. Overall, 388 patients with MRSA bacteraemia were included, 164 cases and 224 controls. According to bivariate analyses, cases were significantly more likely than controls to (i) be older (>65 years), (ii) have transferred from an institution, (iii) have stayed in an ICU, (iv) have had more invasive devices, (v) have a poorer prognosis on admission, (vi) have higher disease severity at the time of bacteraemia, and (vii) have a DAAT of > or = 2 days. Upon multivariate analysis, among patients >65 years, DAAT was significantly associated with increased mortality (p 0.04). Furthermore, patients >65 years with severe sepsis were much more likely to experience DAAT (p 0.02). In elderly patients with MRSA bacteraemia, DAAT is associated with increased mortality. Moreover, advanced age is a predictor for DAAT. These significant epidemiological associations mandate early coverage of MRSA in septic elderly patients.

Outcomes of antifungal prophylaxis in high-risk liver transplant recipients.

Antifungal prophylaxis for liver transplant recipients (LTRs) is common among patients considered at high risk of infection, but optimal prophylaxis duration and drug has not been defined. This study aimed to assess the effects of 14 days of antifungal therapy prophylaxis in reducing proven invasive fungal infections (IFI) in high-risk subjects. Eligible subjects who met 2 or more risk criteria were randomized 1:1 to the treatment arms (liposomal amphotericin B or fluconazole) and were followed for 100 days post transplantation for evidence of IFI. The study was designed to enroll 300 subjects, but was closed early for insufficient enrollment. A total of 71 subjects were enrolled and randomized. Two-thirds of subjects completed 14 days of study therapy. Ten subjects developed proven or probable IFI with Candida species (9 subjects) and Cryptococcus neoformans (1 subject); rates were similar in the 2 treatment arms. Eleven subjects died, but no death was attributed to study drug or IFI. In summary, high-risk LTRs tolerated antifungal prophylaxis well, and rates of IFI were lower than previously reported in untreated high-risk LTRs.

Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia.

OBJECTIVES: To evaluate the clinical characteristics, treatment and outcomes of patients with osteoarticular infections (OAIs) associated with Staphylococcus aureus bacteraemia (SAB). METHODS: The clinical characteristics and outcomes for patients with OAI were described using a post hoc analysis of an open label, randomized trial comparing daptomycin with standard therapy (vancomycin or anti-staphylococcal penicillin with initial gentamicin) for the treatment of SAB. RESULTS: OAI occurred in 32 of 121 patients (21 daptomycin and 11 standard therapy) with complicated SAB (18 septic arthritis, 9 vertebral osteomyelitis and 7 others). Two patients had osteomyelitis in more than one site. Success rates seen in two groups were as follows: vertebral osteomyelitis [3/5 (60%) daptomycin versus 0/2 (0%) comparator], septic arthritis [7/11 (64%) versus 3/5 (60%)], sternal osteomyelitis [3/3 (100%) versus 1/2 (50%)] and long bone osteomyelitis [0/1 (0%) versus 1/1 (100%)]. Success rates in both treatment groups improved with surgical therapy. Creatine phosphokinase elevations to >500 IU/L occurred in one patient on daptomycin who discontinued therapy, whereas renal impairment developed in three patients on standard therapy, two of whom discontinued therapy. Two patients treated with daptomycin and one patient on vancomycin had increases in S. aureus MICs to daptomycin and vancomycin, respectively. Three patients treated with daptomycin died following completion of therapy, with mortality attributed to multiple co-morbid conditions and inadequate debridement of OAIs in these patients. No deaths were reported in the standard therapy group. CONCLUSIONS: Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.

Invasive fungal infections in low-risk liver transplant recipients: a multi-center prospective observational study.

Prevention of invasive fungal infections (IFIs) in orthotopic liver transplant (OLT) recipients utilizing postoperative systemic antifungal prophylaxis, typically with fluconazole, is justified among those at high risk for IFI. Use of postoperative antifungal prophylaxis for low-risk OLT recipients is widely practiced but not universally accepted nor supported by data. We conducted a prospective observational study among 200 OLT recipients who were at low risk for IFI and did not receive postoperative antifungal prophylaxis. Patients were considered low risk if they had /=units of 40 blood products or return to the operating room for intra-abdominal bleeding; return to the operating room for anastomotic leak or vascular insufficiency; preoperative serum creatinine of >/=2 mg/dL; and perioperative Candida colonization. Patients were followed 100 d post-transplantation for evidence of IFI. Of 193 eligible patients, 7 (4%) developed an IFI. Three (2%) IFIs were due to Candida spp. and potentially preventable by standard fluconazole prophylaxis. Three patients developed invasive aspergillosis; one developed late onset disseminated cryptococcosis. Liver transplant recipients at low risk for IFI can be identified utilizing pre-determined criteria, and post-transplantation antifungal prophylaxis can be routinely withheld in these patients.

Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients.

To determine whether fluoroquinolone exposure is a risk factor for the isolation of Staphylococcus aureus and whether the effect is different for methicillin-resistant S. aureus (MRSA) versus methicillin--susceptible S. aureus (MSSA), we studied two case groups. The first case group included 222 patients with nosocomially acquired MRSA. The second case group included 163 patients with nosocomially acquired MSSA. A total of 343 patients admitted concurrently served as controls. Outcome measures were the adjusted odds ratio (OR) for isolation of MRSA and MSSA after fluoroquinolone exposure. Exposure to both levofloxacin (OR 5.4; p <0.0001) and ciprofloxacin (OR 2.2; p < 0.003) was associated with isolation of MRSA but not MSSA. After adjustment for multiple variables, both drugs remained risk factors for MRSA (levofloxacin OR 3.4; p <0.0001; ciprofloxacin OR 2.5; p = 0.005) but not MSSA. Exposure to levofloxacin or ciprofloxacin is a significant risk factor for the isolation of MRSA, but not MSSA.

Adequacy of fellowship training: results of a survey of recently graduated fellows.

The adequacy of fellowship training in the field of infectious diseases was assessed by means of a survey of recently graduated fellows. Surveys were mailed to all individuals who had passed the American Board of Internal Medicine's board certification examination in infectious diseases since 1992. A total of 666 completed surveys were returned by the deadline (response rate, 36%). Although most recent graduates thought that training in the standard components of clinical infectious diseases was adequate, only 50% thought that training in infection control was adequate. Fewer than 1 in 3 believed that they had received adequate training in the business aspects of infectious diseases practice. The adequacy and duration of research training were linked to ultimate career choice. These results form the basis for the Infectious Diseases Society of America's new initiatives to assist with more-diversified and relevant fellowship training.

Clinical effectiveness and cost-effectiveness of 2 management strategies for infected total hip arthroplasty in the elderly.

Optimal management of infected total hip arthroplasty poses a major challenge to clinicians. Exchange arthroplasty is usually advocated but has high rates of surgical morbidity and is expensive. Debridement with prosthesis retention is associated with less morbidity, but high rates of relapsed infection have been described. To estimate the effectiveness and cost-effectiveness of these 2 strategies among older patients, we used a Markov model to simulate patients' projected lifetime clinical course in hypothetical cohorts of 65-year-old and frail 80-year-old men and women. Initial debridement and retention increased life expectancy 2.2-2.6 quality-adjusted life months and had a favorable cost-effectiveness ratio in all cohorts. Results were most sensitive to the annual rate of relapse after debridement and age at initial diagnosis of infection. In the absence of prospective clinical trials, debridement and retention is a reasonable strategy for treatment of older persons with staphylococcal or streptococcal infection and a nonloosened prosthesis.

Nosocomial bloodstream infections: organisms, risk factors, and implications.

In the last 30 years, the frequency, etiology, and epidemiology of bloodstream infections (BSIs) have changed with the evolution of medical care, particularly among the increasing number of hospitalized patients who require intensive care. Although gram-negative bacilli were the predominant nosocomial pathogens in the 1970s, gram-positive cocci have emerged as a more frequent cause of nosocomial BSIs during the 1980s and 1990s. Many gram-positive cocci associated with nosocomial BSIs are now resistant to commonly used antibiotics. Currently, the 3 most common causes of nosocomial BSIs in the United States are coagulase-negative staphylococci, Staphylococcus aureus, and enterococci. The emergence of vancomycin-resistant staphylococcal infections is of particular concern. In addition, the incidence of methicillin-resistant S. aureus (MRSA) infections appears to be increasing; however, the effect of MRSA infection on mortality in hospitalized patients remains unclear. Therefore, newer, more effective antimicrobial therapies are needed to treat BSIs caused by gram-positive cocci are needed.

Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group.

Although fungal urinary tract infections are an increasing nosocomial problem, the significance of funguria is still not clear. This multicenter prospective surveillance study of 861 patients was undertaken to define the epidemiology, management, and outcomes of funguria. Diabetes mellitus was present in 39% of patients, urinary tract abnormalities in 37.7%, and malignancy in 22.2%; only 10.9% had no underlying illnesses. Concomitant nonfungal infections were present in 85%, 90% had received antimicrobial agents, and 83.2% had urinary tract drainage devices. Candida albicans was found in 51.8% of patients and Candida glabrata in 15.6%. Microbiological and clinical outcomes were documented for 530 (61.6%) of the 861 patients. No specific therapy for funguria was given to 155 patients, and the yeast cleared from the urine of 117 (75.5%) of them. Of the 116 patients who had a catheter removed as the only treatment, the funguria cleared in 41 (35.3%). Antifungal therapy was given to 259 patients, eradicating funguria in 130 (50.2%). The rate of eradication with fluconazole was 45.5%, and with amphotericin B bladder irrigation it was 54.4%. Only 7 patients (1.3%) had documented candidemia. The mortality rate was 19.8%, reflecting the multiple serious underlying illnesses found in these patients with funguria.

Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo. The National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group.

Management of candiduria is limited by the lack of information about its natural history and lack of data from controlled studies on the efficacy of treating it with antimycotic agents. We compared fungal eradication rates among 316 consecutive candiduric (asymptomatic or minimally symptomatic) hospitalized patients treated with fluconazole (200 mg) or placebo daily for 14 days. In an intent-to-treat analysis, candiduria cleared by day 14 in 79 (50%) of 159 receiving fluconazole and 46 (29%) of 157 receiving placebo (P<.001), with higher eradication rates among patients completing 14 days of therapy (P<.0001), including 33 (52%) of 64 catheterized and 42 (78%) of 54 noncatheterized patients. Pretreatment serum creatinine levels were inversely related to candiduria eradication. Fluconazole initially produced high eradication rates, but cultures at 2 weeks revealed similar candiduria rates among treated and untreated patients. Oral fluconazole was safe and effective for short-term eradication of candiduria, especially following catheter removal. Long-term eradication rates were disappointing and not associated with clinical benefit.

Fluoroquinolone treatment of skin and skin structure infections.

When the causative pathogens are susceptible, the fluoroquinolones have been demonstrated to be highly efficacious in the treatment of both mild uncomplicated skin and skin structure infections as well as the more severe complicated infections involving these tissues, including infections of the feet of diabetic patients. These broad spectrum agents, particularly the newer fluoroquinolones with enhanced activity against gram-positive bacteria, are ideal for treating the often polymicrobial complicated skin and skin structure infections. The wisdom of treating uncomplicated skin infections, which are primarily due to staphylococci and streptococci wherein more narrow spectrum beta-lactam antibiotics would suffice, is questionable.

Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection.

OBJECTIVE: To define the epidemiology of broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units (ICUs) during a nonoutbreak period, including the prevalence, the risk factors for colonization, the frequency of acquisition, and the rate of infection. DESIGN: Prospective cohort study. SETTING: Tertiary care hospital. PATIENTS: Consecutive patients admitted to two surgical ICUs. MAIN OUTCOME MEASUREMENTS: Serial patient surveillance cultures screened for ceftazidime (CAZ) resistance, antibiotic and hospital exposure, and infections. RESULTS: Of the 333 patients enrolled, 60 (18%) were colonized with CAZ-resistant gram-negative bacilli (CAZ-RGN) at admission. Clinical cultures detected CAZ-RGN in only 5% (3/60) of these patients. By using logistic regression, CAZ-RGN colonization was associated with duration of exposure to cefazolin (odds ratio, 10.3; p < or = .006) and to broad-spectrum cephalosporins/penicillins (odds ratio, 2; p < or = .03), Acute Physiology and Chronic Health Evaluation III score (odds ratio, 1.2; p < or = .008), and previous hospitalization (odds ratio, 3.1; p < or = .006). Of the 100 patients who remained in the surgical ICU for > or = 3 days, 26% acquired a CAZ-RGN. Of the 14 infections caused by CAZ-RGN, 11 (79%) were attributable to the same species present in surveillance cultures at admission to the surgical ICU. CONCLUSIONS: Colonization with CAZ-RGN was common and was usually not recognized by clinical cultures. Most patients colonized or infected with CAZ-RGN had positive surveillance cultures at the time of admission to the surgical ICU, suggesting that acquisition frequently occurred in other wards and institutions. Patients exposed to first-generation cephalosporins, as well as broad-spectrum cephalosporins/penicillins, were at high risk of colonization with CAZ-RGN. Empirical treatment of nosocomial gram-negative infections with broad-spectrum cephalosporins, especially in the critically ill patient, should be reconsidered.

Health and economic outcomes of antibiotic resistance in Pseudomonas aeruginosa.

BACKGROUND: Antimicrobial resistance is an increasing problem. OBJECTIVE: To examine the clinical and economic impact of antibiotic resistance in Pseudomonas aeruginosa. METHODS: In-hospital mortality, secondary bacteremia, length of stay, and hospital charges were examined in a cohort of 489 inpatients with positive clinical cultures for P aeruginosa. One hundred forty-four had a resistant baseline P aeruginosa isolate and 30 had resistance emerge during follow-up. Multivariable and survival analytic methods were used to adjust for confounding and effects of time. RESULTS: The overall in-hospital mortality rate was 7.6%, 7.7% in patients with a resistant isolate at baseline (relative risk [RR], 1.3; 95% confidence interval [CI], 0.6-2.8) and 27% in patients in whom resistance emerged (RR, 3.0; 95% CI, 1.2-7.8). Secondary bacteremia developed in 1.4% of patients in whom resistance did not emerge and in 14% of those in whom resistance emerged (RR, 9.0; 95% CI, 2.7-30). The median duration of hospital stay following the initial P aeruginosa isolate was 7 days. Emergence of resistance, but not baseline resistance, was significantly associated with a longer hospital stay (P<.001 and P=.71, respectively). The average daily hospital charge was $2059. Neither baseline resistance nor emergence of resistance had a significant effect on the daily hospital charge. In a matched cohort analysis, a trend was seen toward increased total charges in patients demonstrating emergence of resistance (difference, $7340; P=.14). CONCLUSIONS: Emergence of antibiotic resistance in P aeruginosa results in severe adverse outcomes. Efforts should be directed toward early detection and prevention of emergence of antibiotic resistance.

Staphylococcus aureus prosthetic valve endocarditis: optimal management and risk factors for death.

The mortality rate associated with Staphylococcus aureus prosthetic valve endocarditis (PVE) remains high. To identify clinical events associated with an increased risk of death among patients with S. aureus PVE and to evaluate the role of valve replacement surgery in reducing mortality, we conducted a retrospective cohort study of patients who met strict criteria for definite S. aureus PVE. The primary endpoint for the study was survival at 3 months from the date of diagnosis. S. aureus PVE was diagnosed in 33 patients. Of these, 14 (42%) died within 90 days of the diagnosis. Cardiac complications were detected in 22 (67%), and central nervous system (CNS) complications were detected in 11 (33%). A stepwise logistic regression multivariate model demonstrated that cardiac complications, but not CNS complications, were associated with increased mortality and that performing valve replacement surgery during antibiotic therapy was associated with decreased mortality. These associations were confirmed by using a Cox proportional hazards model with time-dependent covariates to control for survival bias. Performing valve replacement surgery during antimicrobial therapy will reduce the mortality among patients with S. aureus PVE, even those without evidence of cardiac complications.

Carriage of methicillin-resistant Staphylococcus aureus at hospital admission.

OBJECTIVES: To measure the prevalence of, and to establish predictors for, the nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission. To evaluate mannitol-salt agar with oxacillin for the simultaneous detection and identification of MRSA from nasal swabs. DESIGN: Three-month prospective case-control survey, with data collected from interviews and computerized databases. The criterion standard for MRSA detection was culture on Mueller-Hinton agar with oxacillin 6 microg/mL (National Committee for Clinical Laboratory Standards method). SETTING: 320-bed tertiary-care hospital. PATIENTS: 387 patients screened within 24 hours after admission, including 10 MRSA carriers (cases), 291 patients with no S aureus, and 86 patients with methicillin-susceptible S aureus. RESULTS: The prevalence of MRSA nasal carriage was 2.6%, whereas the prevalence of carriage was 3.1% when both nasal and wound cultures were performed. The significant predictors of carriage were a prior detection of MRSA, open wounds, diabetes mellitus, treatments by injection, prior nursing home stays, visits at home by a nurse, and prior antibiotic treatments. Cases had stayed for longer periods in hospitals and had received longer antibiotic treatments within a year. Eighty patients (including the 10 cases) had diabetes, had been exposed to healthcare facilities within a year, and had antibiotics within 6 months. The sensitivity and negative predictive value of nasal swabs on mannitol-salt agar with oxacillin were 60% and 71%, respectively. CONCLUSION: MRSA carriage on admission to the hospital may be an increasing and underestimated problem. Further studies are needed to develop and validate a sensitive and specific prediction rule.