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Background: Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. Methods: A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). Results: Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. Conclusions: The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.

Background Resistant organisms (ROs) are increasingly implicated in pneumonia in patients presenting to the emergency department (ED). The concept of healthcare-associated pneumonia (HCAP) exists to help identify patients infected with ROs but may be overly broad. We sought to validate a previously developed score for determining the risk for an RO and to compare it with the HCAP definition. Methods We evaluated adult patients admitted via the ED with bacterial pneumonia (January-December 2010). We defined methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and extended-spectrum β-lactamases as ROs. The risk score was as follows: 4, recent hospitalization; 3, nursing home; 2, chronic hemodialysis; 1, critically ill. We evaluated the screening value of the score and of HCAP by determining their areas under the receiver-operating characteristic (AUROC) curves for predicting ROs. Results The cohort included 977 patients, and ROs were isolated in 46.7%. The most common organisms included MRSA (22.7%), P. aeruginosa (19.1%), and Streptococcus pneumoniae (19.1%). The risk score was higher in those with an RO (median score, 4 vs 1; P 0 had a high negative predictive value (84.5%) and could lead to fewer patients unnecessarily receiving broad-spectrum antibiotics. Conclusions ROs are common in patients presenting to the ED with pneumonia. A simple clinical risk score performs moderately well at classifying patients regarding their risk for an RO.

The emerging problem of antibiotic resistance, especially among Gram-negative bacteria (GNB), has become a serious threat to global public health. Very few new antibacterial classes with activity against antibiotic-resistant GNB have been brought to market. Renewed and growing attention to the development of novel compounds targeting antibiotic-resistant GNB, as well as a better understanding of strategies aimed at preventing the spread of resistant bacterial strains and preserving the efficacy of existing antibiotic agents, has occurred. The Gram-Negative Resistance Summit convened national opinion leaders for the purpose of analyzing current literature, epidemiologic trends, clinical trial data, therapeutic options, and treatment guidelines related to the management of antibiotic-resistant GNB infections. After an in-depth analysis, the Summit investigators were surveyed with regard to 4 clinical practice statements. The results then were compared with the same survey completed by 138 infectious disease and critical care physicians and are the basis of this article.

Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection and the leading cause of mortality attributable to these critical infections [ 1– 3]. Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is now a major cause of HAP [ 4– 6]. Rates of clinical failure in patients with HAP due to MRSA are high [ 7, 8]. Currently, only vancomycin and linezolid are recommended for treatment of HAP due to MRSA [ 9]. Results from recent pneumonia trials with new antibiotics active against MRSA have not been encouraging [ 10– 12]. Therefore, additional antistaphylococcal agents for treatment of HAP are urgently needed. Telavancin is a lipoglycopeptide antibacterial agent exhibiting potent, concentration-dependent bactericidal effects via a dual mechanism of action that combines inhibition of cell wall synthesis and disruption of membrane barrier function [ 13– 15]. In vitro, telavancin is rapidly bactericidal against clinically important gram-positive bacteria, including MRSA, vancomycin-intermediate S. aureus, and penicillin-resistant S. pneumoniae [ 13, 16, 17]. Telavancin penetrates well into the epithelial lining fluid and alveolar macrophages of healthy subjects, achieving concentrations up to 8-fold and 85-fold, respectively, above telavancin's minimum inhibitory concentration (MIC) for 90% (MIC90) of MRSA strains (.5 μg/mL) [ 16, 18]. Unlike daptomycin (a cyclic lipopeptide), telavancin remains active in vitro in the presence of pulmonary surfactant [ 16]. Telavancin is approved in the United States and Canada for the treatment of adult patients with complicated skin and skin-structure infections due to susceptible gram-positive pathogens. The current studies were designed to assess the clinical efficacy and safety of telavancin compared with vancomycin in the treatment of HAP due to gram-positive organisms, with a focus on infections due to MRSA. Partial results of these studies have been previously reported.

During the Health Care-Associated Pneumonia Summit conducted in June 2007, it was found that there is a need for educational efforts in several areas of health care-associated infections (HAI) that extend beyond pneumonia. This supplement to Clinical Infectious Diseases represents the proceedings of the HAI Summit, a diverse panel of clinical investigators whose goal was to assess the quality of evidence regarding issues surrounding HAI and to discuss potential implications for its diagnosis and treatment in the future.

Vancomycin is effective against methicillin-resistant Staphylococcus aureus and has been widely used in the past few years. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Vancomycin treatment failure rates are associated with an increase in the minimum inhibitory concentration as well as a decrease in the rate of bacterial killing. The intrinsic limitations of vancomycin also include poor tissue penetration, particularly in the lung; relatively slow bacterial killing; and the potential for toxicity. In addition, intermediate-level vancomycin resistance has emerged among staphylococci, as have rare cases of fully resistant strains. Because of these problems, when using vancomycin, it is probably prudent to carefully establish the diagnosis, test for antimicrobial susceptibility, and monitor serum trough concentrations to ensure adequate dosing.

Successful treatment of patients with nosocomial pneumonia depends primarily on providing adequate initial antibiotic treatment in a timely manner, because an inappropriate course is closely associated with increased mortality. Gram-negative bacteria are commonly responsible for nosocomial pneumonia, and the increasing prevalence of drug resistance among these bacteria complicates decision making with regard to treatment with antibiotics. Infections due to Pseudomonas aeruginosa are particularly problematic because of their intrinsic resistance to multiple classes of antibiotics and their ability to acquire adaptive resistance during a therapeutic course. Numerous strategies, including the use of combination therapy followed by de-escalation of antibiotics, have shown promise in the treatment of these serious infections. However, future success in treating nosocomial infections depends on the appropriate and responsible use of antibiotics in the intensive care unit, to ensure that the antibiotics available today maintain their effectiveness in the future.

Although quinolones are often used to treat nosocomial pneumonia (NP), there have been few trials documenting their efficacy in treating NP. Given the growing use of quinolones and issues regarding resistance, we conducted a meta-analysis of all trials of quinolones for treatment of NP. We identified 5 randomized trials comparing quinolones with other agents used to treat NP. The studies varied in both quality and sample size and included a total of nearly 1200 subjects. Four of the 5 trials used ciprofloxacin, administered every 8 h, whereas the fifth used levofloxacin administered daily. In 3 trials, the comparator agent was imipenem-cilistatin, whereas, in 2 trials, ceftazadime was the comparator agent. The efficacy of quinolones and comparator antibiotics was similar, with a pooled odds ratio for clinical cure of 1.12 (95% confidence interval, 0.80-1.55). Neither microbiological eradication rates nor mortality rates varied on the basis of antimicrobial selection.

Infection-control recommendations include the use of gowns and gloves to prevent horizontal transmission of vancomycin-resistant enterococci (VRE). This study sought to determine whether the use of a gown and gloves gives greater protection than glove use alone against VRE transmission in a medical intensive care unit (MICU). From 1 July 1997 through 30 June 1998 and from 1 July 1999 through 31 December 1999, health care personnel and visitors were required to don gloves and gowns upon entry into rooms where there were patients infected with nosocomial pathogens. From 1 July 1998 through 30 June 1999, only gloves were required under these same circumstances. During the gown period, 59 patients acquired VRE (9.1 cases per 1000 MICU-days), and 73 patients acquired VRE during the no-gown period (19.6 cases per 1000 MICU-days; P

Scheduled rotation of treatment of gram-negative antimicrobial agents has been associated with reduction of serious gram-negative infections. The impact of this practice on other nosocomial infections has not been assessed. The purpose of this study was to determine if scheduled antimicrobial rotation reduced rates of acquisition of enteric vancomycin-resistant enterococci (VRE) among 740 patients admitted to an intensive care unit (ICU). The preferred gram-negative agent was ceftazidime during rotation 1 and ciprofloxacin during rotation 2. Unadjusted VRE acquisition rates were 8.5 cases per 1000 ICU days and 11.7 cases per 1000 ICU days during rotations 1 and 2, respectively (P

Inadequate antimicrobial treatment, generally defined as microbiological documentation of an infection that is not being effectively treated, is an important factor in the emergence of infections due to antibiotic-resistant bacteria. Factors that contribute to inadequate antimicrobial treatment of hospitalized patients include prior antibiotic exposure, use of broad-spectrum antibiotics, prolonged length of stay, prolonged mechanical ventilation, and presence of invasive devices. Strategies to minimize inadequate treatment include consulting an infectious disease specialist, using antibiotic practice guidelines, and identifying quicker methods of microbiological identification. In addition, clinicians should determine the prevailing pathogens that account for the community-acquired and nosocomial infections identified in their hospitals. Clinicians can improve antimicrobial treatment by using empirical combination antibiotic therapy based on individual patient characteristics and the predominant bacterial flora and their antibiotic susceptibility profiles. This broad-spectrum therapy can then be narrowed when initial culture results are received. Further study evaluating the use of antibiotic practice guidelines and strategies to reduce inadequate treatment is necessary to determine their impact on patient outcomes.

There is a general consensus that antimicrobial resistance in the hospital setting has emerged as an important variable that influences patient outcomes and overall use of resources [ 1-3]. Hospitals worldwide are faced with increasingly rapid emergence and spread of antibiotic-resistant bacteria. Antibiotic-resistant strains of both gram-negative bacilli and gram-positive bacteria are reported to be important causes of hospital-acquired infection, including ventilator-associated pneumonia (VAP) [4, 5]. In many cases, few antimicrobial agents remain available for effective treatment, particularly with regard to methicillin-resistant and vancomycin-resistant Staphylococcus aureus and gram-negative bacteria that produce extended-spectrum 3-lactamases and that have resistance to multiple other antibiotics [6-8]. One of the consequences of a greater prevalence of antimicrobial resistance is an increased recognition of inadequate

Challenges in the treatment of serious bacterial infections include the requirement for prompt initiation of appropriate antimicrobial therapy (therapy that is correct on the basis of available clinical, pharmacological, and microbiological data) to minimize morbidity and mortality. Delaying the initiation of appropriate therapy or initiating inappropriate therapy has been shown, in numerous studies of a variety of serious bacterial infections, to be associated with poor outcomes [1-3]. Challenges in the determination of appropriate antimicrobial therapy for serious bacterial infections include an increasing incidence of antimicrobial-resistant pathogens [4-11]. In addition, for most cases of serious bacterial infection, there is little time to determine the right treatment, as time to initiation of effective therapy is a strong predictor of mortality. Thus, initial treatment must be empirical; that is, it must be implemented before pathogen culture and susceptibility results can be obtained.