Impact of Initial Antifungal Therapy on the Outcome of Patients With Candidemia and Septic Shock Admitted to Medical Wards: A Propensity Score-Adjusted Analysis.

BACKGROUND: Echinocandins are recommended as firstline therapy in patients with candidemia. However, there is debate on their efficacy in survival outcomes. The aim of this study is to evaluate whether the choice of initial antifungal therapy improves mortality in patients with candidemia in relation to the presence of septic shock. METHODS: Patients with candidemia hospitalized in internal medicine wards of 5 tertiary care centers were included in the study (December 2012-December 2014). Patient characteristics, therapeutic interventions, and outcome were reviewed. Propensity score (PS) was used as a covariate of the multivariate analysis to perform a stratified analysis according to PS quartiles and to match patients receiving "echinocandins" or "azoles." RESULTS: Overall, 439 patients with candidemia were included in the study. A total of 172 (39.2%) patients had septic shock. Thirty-day mortality was significantly higher in patients with septic shock (45.3%) compared with those without septic shock (31.5%; P = .003). Among patients with septic shock, the use of echinocandins in the first 48 hours, compared with azoles, did not affect 30-day mortality in the PS-adjusted Cox regression analysis (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.37-1.59; P = .48), the PS-stratified analysis, or the logistic regression model in matched cohorts (adjusted HR, 0.92; 95% CI, 0.51-1.63; P = .77). CONCLUSIONS: Echinocandin therapy seems not to improve the outcome of non-intensive care unit patients with septic shock due to candidemia. These findings support the urgent need of further studies in this patient population.

Risk Factors and Outcomes for Bloodstream Infections Secondary to Clostridium difficile Infection.

We determined the incidence, risk factors, and outcomes of bloodstream infections (BSI) subsequent to Clostridium difficile infection (CDI). We performed a retrospective study of all patients with definite diagnosis of CDI admitted from January 2014 to December 2014 in two large hospitals in Rome. Two groups of patients were analyzed: those with CDI and subsequent BSI (CDI/BSI(+)) and those with CDI and no evidence of primary BSI (CDI/BSI(-)). Data about clinical features, microbiology, treatments, and mortality were obtained. Overall, 393 cases of CDI were included in the final analysis: 72 developed a primary nosocomial BSI, while 321 had CDI without microbiological and clinical evidence of BSI. Etiologic agents of BSI were Candida species (47.3%), Enterobacteriaceae (19.4%), enterococci (13.9%), and mixed infections (19.4%). In multivariate analysis, ribotype 027 status (odds ratio [OR], 6.5), CDI recurrence (OR, 5.5), severe CDI infection (OR, 8.3), and oral vancomycin at >500 mg/day (OR, 3.1) were recognized as factors independently associated with the development of nosocomial BSI. Thirty-day mortality from CDI diagnosis was higher for patients of the CDI/BSI(+) group than for the controls (38.9 versus 13.1%; P < 0.001). Among patients of the CDI/BSI(+) group, mortality attributable to primary BSI was as high as 57%. Our findings suggest that severe CDI is complicated by the development of nosocomial BSI. Candida species and enteric bacteria appear to be the leading causative pathogens and are associated with poor outcomes.

Endocarditis caused by nutritionally variant streptococci: a case report and literature review.

Infective endocarditis (IE) due to Abiotrophia and Granulicatella species, previously referred to as nutritionally variant streptococci (NVS), occurs rarely and is often associated with negative blood cultures. Rates of treatment failure, infection relapse and mortality are higher than those of endocarditis caused by other viridans streptococci. We report a case of endocarditis caused by Granulicatella adiacens in a young man with no risk factors, who was successfully treated with surgery and combination antimicrobial chemotherapy, and provide a literature review of endocarditis attributable to these rare species of fastidious gram-positive cocci which have proven exceedingly difficult to treat, with high rates of relapse and therapeutic failure despite in vitro effective antibiotic treatment regimens. Analysis of literature revealed a high prevalence (61%) of valvular heart predisposing conditions associated with endocarditis caused by NVS, such as congenital valvular heart disease or heart valve prosthesis. On the other hand, 39% of cases showed no evidence of risk factors. Combination antimicrobial chemotherapy with penicillin and gentamicin represents the antimicrobial treatment of choice in the management of patients with IE attributable to NVS. Heart valve replacement surgery should be considered in cases of hemodynamic derangement due to significant valve destruction.

Candidal thrombophlebitis of central veins: case report and review.

Although candidemia and central catheter septic thrombosis is quite common, central veins thrombophlebitis caused by Candida spp. is a rarely reported complication in critically ill patients. Here we report a case of thrombophlebitis of the right internal jugular and subclavian veins due to Candida albicans which occurred in a patient admitted in the intensive care unit for major trauma. The individual was eventually cured after prolonged course of antifungal therapy. We also review 24 additional cases of Candida induced central veins thrombophlebitis reported since 1978. A central vein catheter was in place in all 25 patients with 21 (84%) being admitted in an intensive care unit, 22 (88%) were receiving total parenteral nutrition and 23 (92%) undergoing a course of antibiotic therapy. Overall mortality was 16%, including two patients who received no therapy and died. In the group of patients receiving only medical therapy, the mortality rate was 13%, while no deaths were observed among those treated with combined medical and surgical therapy. Literature data suggest that Candida caused central veins thrombophlebitis is a rare and probably underdiagnosed infectious complication of the critically ill patient. Despite the dramatic presentation with persistent candidemia, mortality is low even with a conservative medical approach with prolonged fungicidal therapy through the use of amphotericin B or echinocandins. Thus, the decision for a combined surgical debridement should be assessed for each patient.

Outbreak of Acinetobacter baumannii producing the carbapenem-hydrolyzing oxacillinase OXA-58 in Rome, Italy.

In this study 45 epidemic and sporadic isolates of Acinetobacter baumannii were investigated by antimicrobial resistance, integron identifications and genotyping. Isolates were genotyped by random amplified polymorphism (RAPD) DNA and pulsed-field gel electrophoresis (PFGE). Four different RAPD patterns were observed among the isolates of our collection, further discerned in six PFGE types. Two prevalent genotypes were identified, one corresponding to a carbapenem resistant epidemic clone, causing an outbreak at the intensive care unit of a hospital of Rome. Two class 1 integrons, carrying different gene cassette arrays, were identified among the two prevalent genotypes. Nucleotide analysis of the integron-variable regions revealed the presence of the aacA4, orfO, bla(OXA-20), and aacC1, orfX, orfX', aadA1 gene cassette arrays, respectively. All the carbapenem resistant strains analyzed in this study carried the bla (OXA-58) gene located on plasmids.

Staphylococcus aureus bacteremia in patients with hematologic malignancies: a retrospective case-control study.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus bacteremia (SAB) continues to be a major problem related to both community and nosocomially acquired infection. Nevertheless few data are presently available in literature about this infection in patients with hematologic malignancies. DESIGN AND METHODS: The purpose of this retrospective study was to report further data on the clinical characteristics and outcome of patients with SAB. All episodes of SAB occurring between January 1997 and June 2001 were identified and defined by analysis of the patients' clinical records. RESULTS: The nosocomial mortality rate was only 3.5% and no patient developed secondary complications. Comparison between neutropenic hematologic patients with SAB and neutropenic hematologic patients with Gram-negative bacteremia (GNB) revealed an higher mortality in the latter group (p=0.03); furthermore, severe sepsis and septic shock were more frequent in patients with GNB (p<0.001). Comparison between neutropenic patients with hematologic malignancies and non-neutropenic ones with other underlying diseases revealed significantly higher morbidity and mortality rates in the latter group. Non neutropenic patients seemed to be more susceptible to both early complications, such as severe sepsis or septic shock (p=0.002) and to later ones, such as endocarditis and metastatic abscesses (p=0.02). INTERPRETATION AND CONCLUSIONS: Our results seem to suggest that SAB in patients with hematologic malignancies is often a low inoculum infection associated with negligible morbidity and mortality rates, especially when adequate antistaphylococcal therapy is administered promptly.

[Staphylococcus aureus sepsis in hospitalized non neutropenic patients: retrospective clinical and microbiological analysis]. / Sepsi da Staphylococcus aureus in pazienti ospedalizzati non neutropenici: analisi retrospettiva clinica e microbiologica.

Staphylococcus aureus is one of the leading agents of nosocomial infection among adult patients. The aim of this study was to determine the predisposing factors and secondary complications of Staphylococcus aureus septicemia (SAS) in non neutropenic patients, as well as the predictors of the outcome in non neutropenic patients with SAS. We performed a retrospective study of 56 cases of SAS that occurred from January 1997 through June 2001 in patients hospitalized in medical wards at the Policlinico Umberto I, "La Sapienza" University of Rome; we excluded surgical patients and those admitted to the intensive care unit. The median age was 61.9 years (range 24-89 years), 29 (51%) patients were male, and infection was hospital-acquired in 83.5% of cases. Metastatic infections were found in 12 patients (21.4%), with 6 (10.7%) developing infectious endocarditis; the relapse rate was 8.9%; 30.3% of Staphylococcus aureus isolates were methicillin-resistant. The overall mortality was 41% and the attributable mortality 28.5%. Twenty-nine patients who developed metastatic infections or died for sepsis were compared with 27 patients who did not develop complications. At univariate analysis, the following factors were associated with a complicated course: delay to adequate antibiotic therapy (2.46 vs 1.15 days, p < 0.03), persistent Staphylococcus aureus bacteremia during antibiotic therapy (3.56 vs 1.51 days, p = 0.01), septic shock (58.6 vs 3.7%, p < 0.002), bacteremic pneumonia as the source of bacteremia (17.2 vs 0%, p = 0.02), and the increased severity of illness at the onset of SAS as evaluated using an "illness score" (4.2 vs 2.1, p < 0.002). At multivariate analysis, septic shock (p < 0.01) and delay to adequate antibiotic therapy (p = 0.05) were confirmed as associated with a complicated outcome. SAS in non neutropenic patients is associated with significant morbidity consequent to a high rate of metastatic infectious disease and with a considerable related mortality.