Souha S. Kanj

International Nosocomial Infection Control Consortium report, data summary for 2002-2007, issued January 2008

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from 2002 through 2007 in 98 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study, using Centers for Disease Control and Prevention (CDC) National Nosocomial Infections Surveillance System (NNIS) definitions for device-associated health care-associated infection, we collected prospective data from 43,114 patients hospitalized in the Consortiums hospital ICUs for an aggregate of 272,279 days. Although device utilization in the INICC ICUs was remarkably similar to that reported from US ICUs in the CDCs National Healthcare Safety Network, rates of device-associated nosocomial infection were markedly higher in the ICUs of the INICC hospitals: the pooled rate of central line-associated bloodstream infections (CLABs) in the INICC ICUs, 9.2 per 1000 CL-days, is nearly 3-fold higher than the 2.4-5.3 per 1000 CL-days reported from comparable US ICUs, and the overall rate of ventilator-associated pneumonia was also far higher, 19.5 vs 1.1-3.6 per 1000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 6.5 versus 3.4-5.2 per 1000 catheter-days. Most strikingly, the frequencies of resistance of Staphylococcus aureus isolates to methicillin (MRSA) (80.8% vs 48.1%), Enterobacter species to ceftriaxone (50.8% vs 17.8%), and Pseudomonas aeruginosa to fluoroquinolones (52.4% vs 29.1%) were also far higher in the Consortiums ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 14.3% (CLABs) to 27.5% (ventilator-associated pneumonia).

Current Concepts in Antimicrobial Therapy Against Resistant Gram-Negative Organisms: Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae, Carbapenem-Resistant Enterobacteriaceae, and Multidrug-Resistant Pseudomonas aeruginosa

The development of antimicrobial resistance among gram-negative pathogens has been progressive and relentless. Pathogens of particular concern include extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa. Classic agents used to treat these pathogens have become outdated. Of the few new drugs available, many have already become targets for bacterial mechanisms of resistance. This review describes the current approach to infections due to these resistant organisms and elaborates on the available treatment options.

Fungal infections in lung and heart-lung transplant recipients. Report of 9 cases and review of the literature.

We reviewed the pattern and incidence of fungal infections in patients undergoing lung and heart-lung transplantation at Duke University Medical Center from September 1992 until August 1995, and present here 9 illustrative cases. Of the 73 lung and heart-lung transplant recipients studied, 59 (81%) had positive fungal cultures at some point after transplantation. The cases presented here illustrate that lung transplant recipients are predisposed to a wide variety of fungal infections. The clinical pattern of these infections ranges from asymptomatic to rapidly progressive fatal disease. In addition to the reactivation of previous fungal infections and recent exposure to new environmental sources, the donor lung itself can be the source of fungal infection, as we showed by using molecular epidemiology techniques. Because of the associated morbidity and mortality, efforts should be directed at investigating prophylactic antifungal regimens in lung transplant recipients. Preliminary reports on the use of itraconazole and aerosolized amphotericin B have been encouraging. Prospective randomized studies are needed to assess the safety and cost effectiveness of different regimens. Fungal infections in patients after lung transplantation can significantly impede recovery and lead to substantial mortality.

Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis

BACKGROUND Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. METHODS In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response-ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)-according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. FINDINGS Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19-179, range 2-882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33 amphotericin B-treated matched controls (weighted all-cause mortality: 33% vs 41%; p=0·595). INTERPRETATION Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated. FUNDING Astellas Pharma Global Development, Basilea Pharmaceutica International.

Safety of aerosolized amphotericin B lipid complex in lung transplant recipients

Background. Fungal infections remain an important cause of morbidity and mortality in lung transplant recipients. Aerosolized amphotericin B lipid complex (ABLC) may be more efficacious than conventional amphotericin B in the prevention of fungal infections in animal models, but experience with aerosolized ABLC in humans is lacking. Methods. We conducted a prospective, noncomparative study designed to evaluate safety of aerosolized ABLC in lung or heart-lung transplant recipients. Results. A total of 381 treatments were administered to 51 patients. Complete spirometry records were available for 335 treatments (69 in intubated patients, 266 in extubated patients). ABLC was subjectively well tolerated in 98% of patients. Pulmonary mechanics worsened by 20% or more posttreatment in less than 5% of all treatments. There were no significant adverse events related to study medication in any patient, and 1-year survival for all enrolled patients was 78%. Conclusion. Administration of nebulized ABLC is safe in the short-term and well-tolerated in lung transplant recipients. Additional prospective, randomized studies are needed to determine the efficacy of aerosolized ABLC alone or in conjunction with systemic therapies in the prevention of fungal infections in lung transplant recipients.

2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

Heterogeneous Vancomycin-Intermediate Susceptibility Phenotype in Bloodstream Methicillin-Resistant Staphylococcus aureus Isolates from an International Cohort of Patients with Infective Endocarditis: Prevalence, Genotype, and Clinical Significance

BACKGROUND The significance of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is unknown. Using a multinational collection of isolates from methicillin-resistant S. aureus (MRSA) infective endocarditis (IE), we characterized patients with IE with and without hVISA, and we genotyped the infecting strains. METHODS MRSA bloodstream isolates from 65 patients with definite IE from 8 countries underwent polymerase chain reaction (PCR) for 31 virulence genes, pulsed-field gel electrophoresis, and multilocus sequence typing. hVISA was defined using population analysis profiling. RESULTS Nineteen (29.2%) of 65 MRSA IE isolates exhibited the hVISA phenotype by population analysis profiling. Isolates from Oceania and Europe were more likely to exhibit the hVISA phenotype than isolates from the United States (77.8% and 35.0% vs 13.9%; P < .001). The prevalence of hVISA was higher among isolates with a vancomycin minimum inhibitory concentration of 2 mg/L (P = .026). hVISA-infected patients were more likely to have persistent bacteremia (68.4% vs 37.0%; P = .029) and heart failure (47.4% vs 19.6%; P = .033). Mortality did not differ between hVISA- and non-hVISA-infected patients (42.1% vs 34.8%, P = .586). hVISA and non-hVISA isolates were genotypically similar. CONCLUSIONS In these analyses, the hVISA phenotype occurred in more than one-quarter of MRSA IE isolates, was associated with certain IE complications, and varied in frequency by geographic region.

Impact of International Nosocomial Infection Control Consortium (INICC) Strategy on Central Line–Associated Bloodstream Infection Rates in the Intensive Care Units of 15 Developing Countries

BACKGROUND The International Nosocomial Infection Control Consortium (INICC) was established in 15 developing countries to reduce infection rates in resource-limited hospitals by focusing on education and feedback of outcome surveillance (infection rates) and process surveillance (adherence to infection control measures). We report a time-sequence analysis of the effectiveness of this approach in reducing rates of central line-associated bloodstream infection (CLABSI) and associated deaths in 86 intensive care units with a minimum of 6-month INICC membership. METHODS Pooled CLABSI rates during the first 3 months (baseline) were compared with rates at 6-month intervals during the first 24 months in 53,719 patients (190,905 central line-days). Process surveillance results at baseline were compared with intervention period data. RESULTS During the first 6 months, CLABSI incidence decreased by 33% (from 14.5 to 9.7 CLABSIs per 1,000 central line-days). Over the first 24 months there was a cumulative reduction from baseline of 54% (from 16.0 to 7.4 CLABSIs per 1,000 central line-days; relative risk, 0.46 [95% confidence interval, 0.33-0.63]; P < .001). The number of deaths in patients with CLABSI decreased by 58%. During the intervention period, hand hygiene adherence improved from 50% to 60% (P < .001); the percentage of intensive care units that used maximal sterile barriers at insertion increased from 45% to 85% (P < .001), that adopted chlorhexidine for antisepsis increased from 7% to 27% (P < .001), and that sought to remove unneeded catheters increased from 37% to 83% (P < .001); and the duration of central line placement decreased from 4.1 to 3.5 days (P < .001). CONCLUSIONS Education, performance feedback, and outcome and process surveillance of CLABSI rates significantly improved infection control adherence, reducing the CLABSI incidence by 54% and the number of CLABSI-associated deaths by 58% in INICC hospitals during the first 2 years.

In-Hospital and 1-Year Mortality in Patients Undergoing Early Surgery for Prosthetic Valve Endocarditis

IMPORTANCE There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). OBJECTIVE To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. INTERVENTIONS Valve replacement during index hospitalization (early surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES In-hospital and 1-year mortality. RESULTS Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.

Effectiveness of a multidimensional approach for prevention of ventilator-associated pneumonia in adult intensive care units from 14 developing countries of four continents: Findings of the International Nosocomial Infection Control Consortium

Objectives:The aim of this study was to analyze the effect of the International Nosocomial Infection Control Consortium’s multidimensional approach on the reduction of ventilator-associated pneumonia in patients hospitalized in intensive care units. Design:A prospective active surveillance before–after study. The study was divided into two phases. During phase 1, the infection control team at each intensive care unit conducted active prospective surveillance of ventilator-associated pneumonia by applying the definitions of the Centers for Disease Control and Prevention National Health Safety Network, and the methodology of International Nosocomial Infection Control Consortium. During phase 2, the multidimensional approach for ventilator-associated pneumonia was implemented at each intensive care unit, in addition to the active surveillance. Setting:Forty-four adult intensive care units in 38 hospitals, members of the International Nosocomial Infection Control Consortium, from 31 cities of the following 14 developing countries: Argentina, Brazil, China, Colombia, Costa Rica, Cuba, India, Lebanon, Macedonia, Mexico, Morocco, Panama, Peru, and Turkey. Patients:A total of 55,507 adult patients admitted to 44 intensive care units in 38 hospitals. Interventions:The International Nosocomial Infection Control Consortium ventilator-associated pneumonia multidimensional approach included the following measures: 1) bundle of infection-control interventions; 2) education; 3) outcome surveillance; 4) process surveillance; 5) feedback of ventilator-associated pneumonia rates; and 6) performance feedback of infection-control practices. Measurements:The ventilator-associated pneumonia rates obtained in phase 1 were compared with the rates obtained in phase 2. We performed a time-series analysis to analyze the impact of our intervention. Main Result:During phase 1, we recorded 10,292 mechanical ventilator days, and during phase 2, with the implementation of the multidimensional approach, we recorded 127,374 mechanical ventilator days. The rate of ventilator-associated pneumonia was 22.0 per 1,000 mechanical ventilator days during phase 1, and 17.2 per 1,000 mechanical ventilator days during phase 2.The adjusted model of linear trend shows a 55.83% reduction in the rate of ventilator-associated pneumonia at the end of the study period; that is, the ventilator-associated pneumonia rate was 55.83% lower than it was at the beginning of the study. Conclusion:The implementation the International Nosocomial Infection Control Consortium multidimensional approach for ventilator-associated pneumonia was associated with a significant reduction in the ventilator-associated pneumonia rate in the adult intensive care units setting of developing countries.