Zeina A. Kanafani

Resistance to Antifungal Agents: Mechanisms and Clinical Impact

Despite advances in preventive, diagnostic, and therapeutic interventions, invasive fungal infections cause significant morbidity and mortality in immunocompromised patients. The burden of antifungal resistance in such high-risk patients is becoming a major concern. A better understanding of the mechanisms and clinical impact of antifungal resistance is essential to the prompt and efficient treatment of patients with invasive mycoses and to improving the outcome of such infections. Although recent guidelines have attempted to standardize antifungal susceptibility testing, limitations still exist as a result of the incomplete correlation between in vitro susceptibility and clinical response to treatment. Four major mechanisms of resistance to azoles have been identified, all of which rely on altered gene expression. Mechanisms responsible for polyene and echinocandin resistance are less well understood. In addition to discussing the molecular mechanisms of antifungal resistance, this article elaborates on the concept of clinical resistance, which is critical to the understanding of treatment failure in patients with invasive fungal infections.

Use of Vancomycin or First-Generation Cephalosporins for the Treatment of Hemodialysis-Dependent Patients with Methicillin-Susceptible Staphylococcus aureus Bacteremia

BACKGROUND Because of its ease of dosing, vancomycin is commonly used to treat methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in patients undergoing long-term hemodialysis. Clinical outcomes resulting from such a therapeutic strategy have not been well defined. METHODS We prospectively identified patients undergoing long-term hemodialysis who received a diagnosis of MSSA bacteremia. Clinical outcomes were grouped according to the predominant antibiotic received during their therapy (vancomycin or a first-generation cephalosporin [cefazolin]). Treatment failure (defined as death or recurrent infection) was determined at 12 weeks after the initial positive blood culture results. A multivariable analysis was used to adjust for confounders. RESULTS During an 84-month period, 123 hemodialysis-dependent patients with MSSA bacteremia were identified. Patients receiving vancomycin (n=77) tended to be younger (51 vs. 57 years; P=.06) and had a lower rates of metastatic complications at presentation (11.7% vs. 36.7%; P=.001) than did those receiving cefazolin (n=46). The 2 groups were similar with regard to Acute Physiology and Chronic Health Evaluation II scores, comorbidities, source of infection, type of hemodialysis access, and access removal rates. Treatment failure was more common among patients receiving vancomycin (31.2% vs. 13%; P=.02). In the multivariable analysis, factors independently associated with treatment failure included vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15-13.45) and retention of the hemodialysis access (odds ratio, 4.99; 95% confidence interval, 1.89-13.76). CONCLUSIONS Hemodialysis-dependent patients with MSSA bacteremia treated with vancomycin are at a higher risk of experiencing treatment failure than are those receiving cefazolin. In the absence of patient specific circumstances (e.g., allergy to beta-lactams), vancomycin should not be continued beyond empirical therapy for hemodialysis-dependent patients with MSSA bacteremia.

Telavancin versus Vancomycin for Hospital-Acquired Pneumonia due to Gram-positive Pathogens

The results from two methodologically identical double-blind studies indicate that telavancin is noninferior to vancomycin based on clinical response in the treatment of hospital-acquired pneumonia due to Gram-positive pathogens.

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.

Severe Surgical Site Infection in Community Hospitals: Epidemiology, Key Procedures, and the Changing Prevalence of Methicillin‐Resistant Staphylococcus aureus

OBJECTIVE To characterize the epidemiology of severe (ie, nonsuperficial) surgical site infection (SSI) in community hospitals. METHODS SSI data were collected prospectively at 26 community hospitals in the southeastern United States. Two analyses were performed: (1) a study of the overall prevalence rates of SSI and the prevalence rates of SSI due to specific pathogens in 2005 at all participating hospitals and (2) a prospective study of consecutive surgical procedures at 9 of the 26 community hospitals from 2000 through 2005. RESULTS In 2005, a total of 1,010 SSIs occurred after 89,302 procedures (prevalence rate, 1.13 infections per 100 procedures). Methicillin-resistant S. aureus (MRSA) was the pathogen most commonly recovered (from 175 SSIs). Trend data from 2000 through 2005 demonstrated that the prevalence rate of MRSA SSI almost doubled during this period, increasing from 0.12 infections per 100 procedures (95% confidence interval [CI], 0.12-0.13) to 0.23 infections per 100 procedures (95% CI, 0.22-0.24) (P<.0001). In adjusted analysis, MRSA SSI was significantly more prevalent at the end of the study period than at the beginning (prevalence rate ratio, 1.48 [95% CI, 1.36-1.61]; P<.0001). CONCLUSIONS MRSA was the pathogen that most commonly caused SSI in our network of community hospitals during 2005. The prevalence of MRSA SSI has increased significantly over the past 6 years.

Underresourced Hospital Infection Control and Prevention Programs: Penny Wise, Pound Foolish?

OBJECTIVES To estimate the cost of healthcare-associated infections (HAIs) in a network of 28 community hospitals and to compare this sum to the amount budgeted for infection control programs at each institution and for the entire network. DESIGN We reviewed literature published since 1985 to estimate costs for specific HAIs. Using these estimates, we determined the costs attributable to specific HAIs in a network of 28 hospitals during a 1-year period (January 1 through December 31, 2004). Cost-saving models based on reductions in HAIs were calculated. SETTING Twenty-eight community hospitals in the southeastern region of the United States. RESULTS The weight-adjusted mean cost estimates for HAIs were

Candida infective endocarditis

25,072 per episode of ventilator-associated pneumonia,

Pyogenic spondylodiscitis: An overview

23,242 per nosocomial blood stream infection,

Underlying mechanisms of carbapenem resistance in extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Escherichia coli isolates at a tertiary care centre in Lebanon: role of OXA-48 and NDM-1 carbapenemases

10,443 per surgical site infection, and

VENTILATOR-ASSOCIATED PNEUMONIA AT A TERTIARY-CARE CENTER IN A DEVELOPING COUNTRY: INCIDENCE, MICROBIOLOGY, AND SUSCEPTIBILITY PATTERNS OF ISOLATED MICROORGANISMS

758 per catheter-associated urinary tract infection. The median annual cost of HAIs per hospital was