A clinical risk index for Clostridium difficile infection in hospitalised patients receiving broad-spectrum antibiotics.

Identification of a population at high risk for Clostridium difficile infection (CDI) would enable CDI prevention strategies to be designed. The purpose of this study was to create a clinical risk index that would predict those at risk for CDI. A CDI risk index was therefore developed, based on a cohort of hospital patients given broad-spectrum antibiotics, and divided into a development and validation cohort. Logistic regression equations helped identify significant predictors of CDI. A scoring algorithm for CDI risk was created using identified risk factors and collapsed to create four categories of CDI risk. The area under the receiver operating characteristic (aROC) curve was used to measure goodness-of-fit. Among 54 226 patients, 392 tested positive for C. difficile. Age 50-80 years [odds ratio (OR: 0.5; P<0.0116)], age >80 years (OR: 2.5; P<0.0001), haemodialysis (OR: 1.5; P=0.0227), non-surgical admission (OR: 2.2; P<0.0001) and increasing length of stay in the intensive care unit (OR: 2.1; P<0.0001) were significantly associated with CDI. A simple risk index using presence of significant variables was significantly associated with increasing risk for CDI in both development (OR: 3.57; P<0.001; aROC: 0.733) and validation (OR: 3.31; P<0.001; aROC: 0.712) cohorts. An OR-derived risk index did not perform as well as the simple risk index. This easily implemented risk index should allow stratification of patients into risk group categories for development of CDI and help fashion preventive strategies.

Disseminated histoplasmosis manifesting as a soft-tissue chest wall mass in a heart transplant recipient.

Soft-tissue masses are rarely associated with Histoplasma capsulatum infection. We describe a heart transplant patient who presented with a large right-sided chest wall mass as a manifestation of disseminated histoplasmosis. A successful clinical outcome was achieved upon recognition of the fungal pathogen.

Interrupted time series analysis of vancomycin compared to cefuroxime for surgical prophylaxis in patients undergoing cardiac surgery.

The increased incidence of methicillin-resistant Staphylococcus aureus (MRSA), the emergence of community-acquired MRSA, and the continued high incidence of methicillin-resistant Staphylococcus epidermidis have required that certain institutions choose vancomycin for surgical prophylaxis. However, the data supporting the use of vancomycin for surgical prophylaxis are controversial. The purpose of this project was to assess the effect of the change from cefuroxime to vancomycin for surgical site infection (SSI) rates in patients undergoing coronary artery bypass graft (CABG) surgery. The monthly rates of SSIs from 2001 to 2005 were analyzed before and after a change from cefuroxime to vancomycin antibiotic prophylaxis in patients undergoing CABG by using an interrupted time series analysis. Patients who underwent cardiac valve replacement surgery and who had received vancomycin during the entire study period were used as a comparator group. A total of 6,465 patients underwent CABG surgery (n = 4,239) or valve replacement surgery (n = 2,226) during the study period. On average, the monthly SSI incidence rate in patients undergoing CABG surgery decreased by 2.1 cases per 100 surgeries after the switch from cefuroxime to vancomycin (P = 0.042) when patients undergoing valve replacement were used as a comparator group. The change in SSI rates was associated with a decrease in the incidence of infections caused by coagulase-negative Staphylococcus and MRSA isolates, with little change in the incidence of SSIs due to other gram-positive organisms or gram-negative organisms. In institutions with a high incidence of methicillin-resistant Staphylococcus species, this study provides evidence for the clinical efficacy of vancomycin prophylaxis for the prevention of postoperative SSIs in patients undergoing CABG surgery.

Prevalence of type III secretion protein exoenzymes and antimicrobial susceptibility patterns from bloodstream isolates of patients with Pseudomonas aeruginosa bacteremia.

The purpose of this study was to determine the prevalence of two type III secretion effector proteins, exoU and exoS from bloodstream isolates of hospitalized patients with Pseudomonas aeruginosa (PSA) bacteremia, to characterize antimicrobial susceptibility patterns, and to compare mortality rates. PSA bloodstream isolates and antibiotic susceptibility profiles were collected from a university-affiliated hospital. ExoS and exoU genes were detected by polymerase chain reaction. Hospital mortality was assessed by medical chart review. 119 of 122 (97.5%) PSA bloodstream isolates contained either the exoS or exoU genes. ExoS was the most prevalent (n=86; 70.5%) followed by exoU (n=31; 25.4%), both genes (n=2; 1.6%) or neither gene (n=3; 2.5%). Isolates containing the exoU gene were significantly more likely to be resistant to cefepime, ceftazidime, piperacillintazobactam, carbapenems, fluoroquinolones, and gentamicin (p<0.05 for all). Mortality was high in patients with PSA bacteremia and did not differ among patients infected with the exoS isolates (n=37; 43%) or exoU isolates (n=11; 35%). One of two type III secretion effector proteins were almost universally present in PSA bloodstream isolates. Isolates containing the exoU gene were more likely to be resistant to multiple antibiotics.

Prevalence of AmpC over-expression in bloodstream isolates of Pseudomonas aeruginosa.

This study examined the contribution of AmpC over-expression to beta-lactam resistance in clinical isolates of Pseudomonas aeruginosa obtained from a hospital in Houston, TX, USA. Seventy-six non-repeat bloodstream isolates obtained during 2003 were screened for ceftazidime resistance in the presence and absence of clavulanic acid 4 mg/L. AmpC was identified by isoelectric focusing (with and without cloxacillin inhibition); stable derepression was ascertained phenotypically by a spectrophotometric assay (with and without preceding induction by imipenem) using nitrocefin as the substrate, and was confirmed subsequently by quantitative RT-PCR of the ampC gene. The clonal relatedness of the AmpC-over-expressing isolates was assessed by pulsed-field gel electrophoresis. In addition, the ampC and ampR gene sequences were determined by PCR and sequencing. For comparison, two standard wild-type strains (PAO1 and ATCC 27853) and three multidrug-susceptible isolates were used as controls. AmpC over-expression was confirmed in 14 ceftazidime-resistant isolates (overall prevalence rate, 18.4%), belonging to seven distinct clones. The most prevalent point mutations in ampC were G27D, V205L and G391A. Point mutations in ampR were also detected in eight ceftazidime-resistant isolates. AmpC over-expression appears to be a significant mechanism of beta-lactam resistance in P. aeruginosa. Understanding the prevalence and mechanisms of beta-lactam resistance in P. aeruginosa may guide the choice of empirical therapy for nosocomial infections in hospitals.

Epidemiology and incidence of Clostridium difficile-associated diarrhoea diagnosed upon admission to a university hospital.

Patients with Clostridium difficile-associated diarrhoea (CDAD) may initially develop symptoms in the community and be subsequently diagnosed at hospital admission. At the present time there is no national surveillance system and no standardized case definition of CDAD in the USA, and baseline data on the incidence and epidemiology of CDAD are scarce. The objective of this study was to report the incidence of CDAD at a tertiary care hospital, and to determine the epidemiology of cases diagnosed within 48h of hospital admission, compared with cases of nosocomial CDAD diagnosed 48h or more after hospitalization. The average incidence was 4.0 cases/10 000 patient-days for CDAD on admission and 7.0 cases/10 000 patient-days for nosocomial CDAD. A significant difference was observed in CDAD rates on admission compared with nosocomial CDAD rates (P=0.017), but no differences were observed over time for either rate. Overall, 44% of cases had CDAD on admission and 56% of cases had nosocomial CDAD. Fifty-six (62%) patients with CDAD on admission had been admitted to the same hospital and 24 (27%) had been admitted to another hospital within the previous 90 days. Only eight (9%) patients had not been exposed to any healthcare services in the 90 days preceding hospital admission. A standardized case definition of healthcare-associated CDAD should include previous hospitalizations. Admitting physicians should consider C. difficile in the differential diagnosis of patients admitted with diarrhoea, with or without a history of admission to healthcare facilities.

Comparison of risk factors for candidemia versus bacteremia in hospitalized patients.

BACKGROUND: Classic risk factors for candidemia include use of total parenteral nutrition (TPN), hospital location, use of central venous catheter, and others. Unfortunately, most of these variables are now also risk factors for antibiotic-resistant bacteria. Thus, use of these risk factors to identify patients at high risk for candidemia is difficult. The purpose of this study was to compare these classic risk factors for candidemia in patients with bloodstream infections to determine the relative strength of these predictors in differentiating patients with candidemia and bacteremia. METHODS: Clinical data were collected from the medical charts of patients who had been hospitalized between 2002 and 2004. Patients with their first episode of candidemia or bacteremia during their hospital stays were included. Risk factors were assessed using a multivariate logistic regression model and internally validated using a bootstrap analysis. A p-value < 0.05 was considered significant. RESULTS: A total of 164 patients (82 with candidemia) were evaluated. According to the logistic analysis, patients who had stayed in the intensive care unit (ICU) (OR = 6.24; 95% CI: 2.58-15.09) or had been using TPN (OR = 4.69; 95% CI: 1.76-12.48) were more likely to have candidemia than bacteremia. While patients with pulmonary (OR = 0.15; 95% CI: 0.055-0.39) or cardiac disease (OR = 0.21; 95% CI: 0.086-0.51) had a greater chance to have bacteremia than candidemia (p < 0.01 for all variables). These results were further validated using bootstrap analysis. CONCLUSION: Among classic risk factors for candidemia, the ICU location at the time of culture and TPN use were most predictive of candidemia while certain medical disorders predicted patients at the highest risk for bacteremia. These results can be used to help identify patients most likely to benefit from empiric antifungal therapy.

Risk factors for postoperative chest wound infections due to gram-negative bacteria in cardiac surgery patients.

Gram-negative bacteria account for up to 35% of postoperative sternal wound infections (SWI) in patients undergoing cardiac surgery. Despite this, risk factors for Gram-negative SWI have not been investigated. The objective of this study was to define risk factors associated with Gram-negative SWI in patients undergoing cardiac surgery. 2590 patients undergoing cardiac surgery between 2002-2005 were prospectively monitored for development of SWI. Patient, operative, and post-operative risk factors were compared among patients that developed Gram-negative SWI and Gram-positive SWI to uninfected controls using univariate and multivariate analysis. A p < 0.05 was considered significant. Surgical site infections developed in 152 (5.9%) patients. Isolates were recovered from the sternum for 128 (5.0%) patients, from the leg donor site for 19 (0.73%) patients, and from the sternum and donor site for 5 (0.19%) patients. Gram-positive pathogens were isolated from 83 (3.3%) patients, Gram-negative pathogens from 42 (1.6%) patients, and mixed pathogens from 27 (1.0%) patients. Hospital admission greater than 48 hours before surgery (OR: 2.25; 95% CI: 1.11 - 4.58), ventilator-dependency preoperatively (OR: 5.32 95% CI: 2.22 - 12.75), and thoracentesis procedure postoperatively (OR: 3.71; 95% CI: 1.45 - 9.49) and diabetes (OR: 2.04; 95% CI: 1.17 - 3.55) were identified as significant risk factors for SWI due to Gram-negative bacteria using multivariate logistic regression. Diabetes, increased age, and peripheral vascular disease were identified as significant risk factors for SWI due to Gram-positive bacteria (p < 0.05, each). The risk factors associated with Gram-negative SWI differed significantly from those associated with Gram-positive SWI. Risk factors associated with Gram-negative SWI were identified. Unique interventions may be necessary to prevent Gram-negative SWI in cardiac surgery patients.

Prevalence of nasal colonization with methicillin-resistant Staphylococcus aureus in selected patient populations.

Methicillin-resistant Staphylococcus aureus nasal colonization was investigated in patients arriving for elective cardiovascular surgery, renal patients admitted for arteriovenous graft surgery, and patients transferred to our hospital from other institutions. Renal patients were significantly more likely to be colonized and represent a potential source of MRSA to our institution.

Multicenter, randomized study comparing levofloxacin and ciprofloxacin for uncomplicated skin and skin structure infections.

BACKGROUND: The fluoroquinolone, levofloxacin, is active against most common pathogens in skin and skin structure infections. METHODS: The efficacy, tolerability, and safety of levofloxacin and ciprofloxacin were compared in a randomized, open-label, multicenter trial of patients with uncomplicated skin and skin structure infections. Of 469 patients treated, 231 received levofloxacin (500 mg qd) and 238 were given ciprofloxacin (500 mg bid). RESULTS: Overall clinical success rates (cured plus improved) for levofloxacin and ciprofloxacin were 98% and 94%, respectively (95% confidence interval [CI], -7.7, 0.7). Overall microbiologic eradication rates by patient were 98% in the levofloxacin group and 89% in the ciprofloxacin group (95% CI, -14.5, -2.7), whereas eradication rates by pathogen were 98% and 90%, respectively (95% CI, -12.6, -3.7). The eradication rate for Staphylococcus aureus was 100% in the levofloxacin group and 87% in the ciprofloxacin group (95% CI, -20.2, -5.1). Treatment-emergent adverse events were comparable, with drug-related adverse events reported in 6% of levofloxacin patients and 5% of ciprofloxacin patients. CONCLUSIONS: Levofloxacin is as effective and safe as ciprofloxacin in the treatment of uncomplicated skin and skin structure infections.

Management of osteomyelitis.

Early diagnosis and aggressive treatment, which includes thorough debridement and culture-directed antibiotic therapy, are essential for effective management of patients with osteomyelitis. Definitive diagnosis of osteomyelitis usually requires microbial culture of bone specimens obtained either by surgery or by percutaneous needle biopsy. The most common pathogen involved in osteomyelitis is Staphylococcus aureus; however, other organisms, including gram-negative pathogens and coagulase-negative staphylococci, may be found. Often, bone infections may be polymicrobial. Antimicrobial therapy, ideally initiated after complete surgical debridement and microbial confirmation of the diagnosis, is usually maintained for at least 6 weeks. Although therapy has traditionally been administered parenterally during an extended hospital stay, oral antibiotic therapy (often following initial parenteral therapy) and parenteral therapy on an outpatient basis are gaining acceptance for use in patients with osteomyelitis.

Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature.

We conducted a prospective, randomized, multicenter study comparing fluconazole and amphotericin B in the treatment of candidal infections. One hundred and sixty-four patients (60 of whom were neutropenic) with documented or presumed invasive candidiasis were assigned to treatment with either fluconazole (400 mg daily) or amphotericin B (25-50 mg daily; 0.67 mg/kg daily for neutropenic patients). Clinical response and survival rates were assessed at 48 hours, after 5 days, and at the end of therapy. Overall response rates to fluconazole and amphotericin B were similar (66% and 64%, respectively). There were no differences in response as related to site of infection, pathogen, time to defervescence, relapse, or survival rates between the groups. Adverse effects were more frequent with amphotericin B (35%) than with fluconazole (5%; P < .0001). The results of this study confirm that fluconazole is as effective as but better tolerated than amphotericin B in the treatment of candidal infections.

Scopulariopsis endocarditis associated with Duran ring valvuloplasty.

Fungal endocarditis is rare and is usually caused by Aspergillus and Candida species. We present a patient with endocarditis caused by Scopulariopsis brevicaulis. The patient had a history of mitral valve disease and, 1 year earlier, had undergone valvuloplasty with the placement of a prosthetic Duran ring in the mitral valve position. S. brevicaulis was cultured from samples of a large vegetation on the mitral valve apparatus. The mitral valve was replaced with a St. Jude mechanical prosthesis. The patient was treated with amphotericin B but was later switched to oral itraconazole when antibiotic tests indicated susceptibility to that agent. We believe this is the 1st reported case of endocarditis caused by Scopulariopsis.

Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only.

The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.

Dermatologic manifestations of infectious diseases in cardiac transplant patients.

Infection remains a significant cause of morbidity and mortality in cardiac transplant patients. Skin infections are not uncommon in these patients. Although usually caused by secondary dissemination after initial infection of another organ system, some skin infections may be primary infections, such as bacterial infections caused by the use of intravenous catheters or fungal infections in severely immunosuppressed patients. Nevertheless, the presence of skin lesions in a transplant patient may indicate infection in a primary site or another deep-seated focus of infection.

Fluconazole susceptibilities of Candida species and distribution of species recovered from blood cultures over a 5-year period.

The distribution and fluconazole susceptibilities of Candida species isolated over a 5-year period were investigated. Susceptibilities were determined by using a new microtiter procedure and the National Committee for Clinical Laboratory Standards (NCCLS) proposed standard. The new method correlated well with the NCCLS proposed standard and gave very clear end points. Results indicate that there are species-related differences in MICs as reflected in the MICs for 90% of species tested. Candida albicans is most susceptible to fluconazole, while Candida glabrata is among the least susceptible. These findings coincided with the observation of a shift in distribution of yeast species recovered from blood cultures from 1987 to 1992. C. albicans was the predominant species (87%) in the pre- or early fluconazole years but decreased to only 31% of the isolates in 1992. Thus, Candida species for which MICs of fluconazole were higher have become more prominent in recent years. Significantly, throughout this period, MICs for each species did not change appreciably.

Prosthetic valve endocarditis resulting from nosocomial bacteremia. A prospective, multicenter study.

OBJECTIVE: To determine the incidence of endocarditis in bacteremic patients with prosthetic heart valves and the risk factors for and the effect of duration of antibiotic therapy on development of endocarditis in such patients. DESIGN: Multicenter, prospective observational study. SETTING: Six university teaching hospitals with high-volume cardiothoracic surgery. PARTICIPANTS: One hundred seventy-one consecutive patients with prosthetic heart valves who developed bacteremia during hospitalization. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated when they were identified as having bacteremia and 1, 2, 6, and 12 months after its occurrence. Of 171 patients, 74 (43%) developed endocarditis: Fifty-six (33%) had prosthetic valve endocarditis at the time bacteremia was discovered ("endocarditis at outset"), whereas 18 (11%) developed endocarditis a mean of 45 days after bacteremia was discovered ("new endocarditis"). Mitral valve location and staphylococcal bacteremia (Staphylococcus aureus or S. epidermidis) were significantly associated with the development of "new" endocarditis. All 18 cases of new endocarditis were nosocomial, and in 6 of these cases (33%) bacteremia was acquired via intravascular devices. Twenty-one patients without evidence of endocarditis at the time of bacteremia received short-term antibiotic therapy (< 14 days); 1 patient (5%) developed endocarditis. Eleven of 70 patients (16%) who received long-term antibiotic therapy (> 14 days) developed endocarditis (P > 0.2). CONCLUSIONS: Bacteremic patients with prosthetic heart valves were at notable risk for developing endocarditis, even when they received antibiotic therapy before endocarditis developed and regardless of the duration of such therapy. Intravascular devices were a common portal of entry.

Cardiac transplantation and related infections.

Infection is a serious cause of morbidity and mortality in the cardiac transplant patient. Early infections within the first month after transplantation are usually caused by nosocomial pathogens, such as Pseudomonas aeruginosa, Staphylococcus aureus, Enterococci, and members of Enterobacteriaceae and include pneumonia, urinary-tract and would infections, and bacteremia associated with the use of intravascular devices. Late infections, usually occurring after the first month and within the first year of transplantation, are commonly caused by cytomegalovirus, Pneumocystis carinii, Legionella, and fungi. Because cardiac transplantation has become a well-established treatment for patients with end-stage heart disease, more physicians will be treating these patients and will need to be familiar with the types of infectious complications associated with transplantation.

Diagnosis and management of the diabetic foot ulcer.

Infected leg ulcers in patients with diabetes mellitus are a common and potentially serious problem. Neuropathy and vascular disease associated with diabetes mellitus allow the possibility of significant microbial invasion. Infections in diabetic patients are usually polymicrobial reflecting the normal flora of the foot skin. Curettage of the base of foot ulcers and deep tissue cultures are the most reliable methods for identifying the true pathogens, which are aerobic Gram-negative bacilli, anaerobes, and Staphylococcus aureus. Empirical antibiotic therapy should be directed against these pathogens. Once culture and sensitivity results are available, therapy should be targeted specifically for the pathogens present to prevent long-term use of broad-spectrum antibiotics. Preventive care of the foot in patients with diabetes mellitus is extremely important and may reduce complications associated with infections of the foot.

Prescribing considerations in fluoroquinolone therapy.

Comparative trials have shown that the new oral fluoroquinolones are as effective as parenteral cephalosporins and other broad-spectrum agents in treating infections of the urinary tract, lower respiratory tract, and skin and skin structure caused by most gram-negative and selected gram-positive pathogens. The agents are also effective in the treatment of prostatitis and osteomyelitis. Sequential parenteral to oral therapy has also proved useful, even in patients who are severely ill and are in intensive care units. This allows patients to be transferred out of intensive care earlier, reduces hospital stay and pharmacy costs, and improves quality of life. Because of the high bioavailability (> 95%) of ofloxacin, oral and parenteral doses are identical.