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Staphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections and the most frequent invasive infection due to methicillin-resistant S. aureus (MRSA). Treatment is challenging, particularly for MRSA, because of limited treatment options. Telavancin is a bactericidal lipoglycopeptide antibiotic that is active against a range of clinically relevant gram-positive pathogens including MRSA. In experimental animal models of sepsis telavancin was shown to be more effective than vancomycin. In clinically evaluable patients enrolled in a pilot study of uncomplicated SAB, cure rates were 88% for telavancin and 89% for standard therapy. Among patients with infection due to only gram-positive pathogens enrolled in the 2 phase 3 studies of telavancin for treatment of hospital-acquired pneumonia, cure rates for those with bacteremic S. aureus pneumonia were 41% (9/22, telavancin) and 40% (10/25, vancomycin) with identical mortality rates. These data support further evaluation of telavancin in larger, prospective studies of SAB., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Antibiotic overuse is of great public health concern. This study assessed whether intervention among physicians and their treated population could achieve a sustained reduction in antibiotic use, specifically in classes known to promote antibiotic resistance among children in a community setting., Methods: We performed a cluster randomized controlled multifaceted trial among 52 primary care pediatricians and the 88,000 children registered in their practices. The intervention was led by local leaders and engaged the participating physicians. It included physician focus group meetings, workshops, seminars, and practice campaigns. These activities focused on self-developed guidelines, improving parent and physician knowledge, diagnostic skills, and parent-physician communication skills that promoted awareness of antibiotic resistance. The main outcome measure was the change in annual antibiotic prescription rates (APRs) of children treated by the intervention group physicians as compared with rates among those treated by control group physicians. The study comprised a 2-year pre-intervention period, a 3-year intervention period, and a 1-year follow-up period. Mixed-effect models were used to assess risk ratios to account for the clustered study design., Results: A decrease in the total APR among children treated by the intervention physicians compared with those treated by the control physicians was observed in the first intervention year (APR decrease among control physicians, 40%; APR decrease among intervention physicians, 22%; relative risk [RR], .76; 95% confidence interval [CI], .75-.78). This reduction crossed over all antibiotic classes but was most prominent for macrolides (macrolide prescription rate among control physicians, 58%; macrolide prescription rate among intervention physicians, 27%; RR, .58; 95% CI, .55-.62). The effect was sustained during the 4 following years. CONCLUSIONS. Multifaceted intervention that engages the physicians in an educational process is effective in reducing APRs and can be sustained., Clinical Trials Registration: NCT01187758., (© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.)

Background: Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens., Methods: Two methodologically identical, double-blind studies (0015 and 0019) were conducted involving patients with hospital-acquired pneumonia (HAP) due to gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 7-21 days. The primary end point was clinical response at follow-up/test-of-cure visit., Results: A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure rates with telavancin versus vancomycin were 58.9% versus 59.5% (95% confidence interval [CI] for the difference, -5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference, -4.3% to 7.7%). Treatment with telavancin achieved higher cure rates in patients with monomicrobial S. aureus infection and comparable cure rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the difference, -0.7% to 10.6%) for study 0015 and 18.5% versus 20.6% (95% CI for the difference, -7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%)., Conclusions: The primary end point of the studies was met, indicating that telavancin is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens.

The increased incidence over the past decade of bloodstream infections (BSIs) caused by gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus, highlights the critical need for a consistent approach to therapy. However, there is currently no international consensus on the diagnosis and management of gram-positive BSIs. The Clinical Consensus Conference on Gram-Positive Bloodstream Infections was convened as a session at the 9th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections held in 2007. Participants discussed various aspects of the practical treatment of patients who present with gram-positive BSI, including therapeutic options for patients with BSIs of undefined origin, the selection of appropriate empirical therapy, and treatment of complicated and uncomplicated BSIs. The opinions of participants about these key issues are reflected in this article.

The determinants of the negative association between Streptococcus pneumoniae and Stapylococcus aureus colonization are unknown. In this matched case-control study, the odds of co-colonization with S. aureus were significantly lower for individuals carrying a piliated versus a nonpiliated S. pneumoniae strain, suggesting the pilus may be a determinant of the negative association.

A recent increase in staphylococcal infections caused by methicillin-resistant Staphylococcus aureus (MRSA), combined with frequent, prolonged ventilatory support of an aging, often chronically ill population, has resulted in a large increase in cases of MRSA pneumonia in the health care setting. In addition, community-acquired MRSA pneumonia has become more prevalent. This type of pneumonia historically affects younger patients, follows infection with influenza virus, and is often severe, requiring hospitalization and causing the death of a significant proportion of those affected. Ultimately, hospital-acquired MRSA and community-acquired MRSA are important causes of pneumonia and present diagnostic and therapeutic challenges. Rapid institution of appropriate antibiotic therapy, including linezolid as an alternative to vancomycin, is crucial. Respiratory infection-control measures and de-escalation of initial broad-spectrum antibiotic regimens to avoid emergence of resistant organisms are also important. This article reviews the clinical features of, diagnosis of, and therapies for MRSA pneumonia.

Background: In March 2002, a patient in Tel Aviv, Israel, died of endocarditis caused by Phialemonium curvatum. As part of his therapy for erectile dysfunction, the patient had been trained to self-inject a compound of vasoactive drugs provided by an impotence clinic into his penile corpus cavernosous., Methods: We identified the used prefilled syringes as the source of his infection. Similar cases were investigated as a putative outbreak of P. curvatum invasive disease among customers of this impotence clinic. P. curvatum isolates, cultured from samples obtained from the patients and from prefilled syringes, were compared by DNA sequencing of the nuclear ribosomal internal transcribed spacer., Results: We identified 2 additional customers at the impotence clinic who had P. curvatum endocarditis. In addition, cultures of unused, prefilled syringes and bottles provided by the same clinic to 5 asymptomatic customers tested positive for pathogenic molds (P. curvatum in 4 cases and Paecilomyces lilacinus in 1). All P. curvatum isolates were of a single genetic type that is known only from this outbreak but is closely related to 3 other P. curvatum genotypes associated with pathogenicity in humans., Conclusions: P. curvatum is an emerging pathogen that can be readily isolated from blood. We identified an outbreak of P. curvatum endocarditis among men who had erectile dysfunction treated by intracavernous penile injections from contaminated prefilled syringes.

The rate of Streptococcus pneumoniae carriage among adults was compared with that among children (age, < or =6 years) in the same population. Nasopharyngeal culture results for 1300 adults and 404 children were analyzed. S. pneumoniae was carried by only 4% of the adults, compared with 53% of children in the same community. Young age, day care center attendance, having young siblings, and no antibiotic use during the month before screening were associated with the high carriage rate among children, whereas the only risk factor associated with carriage among adults was the presence of a respiratory infection on the screening day. S. pneumoniae serotype distribution and antibiotic resistance patterns differed between adults and children. Isolates of the same serotype--even of the same clone--differed in their antibiotic susceptibility patterns between children and adults. In a subanalysis of 151 pairs of children and their parents and of 32 pairs of siblings, intrafamilial transmission of S. pneumoniae could not be demonstrated.

There is growing pressure to demonstrate the value of practice guidelines. We have reviewed the evidence that guidelines for the treatment of community-acquired pneumonia (CAP) change current practices and that the standardization of practices reduces costs and/or improves outcome. The most obvious barrier to implementation of the guidelines is lack of knowledge about their content; equally important are the attitudes and behavior of professionals, patients, and their caregivers. Guidelines may improve the outcome of CAP, provided that there is an association between variations in outcome and some specific processes of care. Conversely, when there is no such relationship, guidelines may reduce the cost of care without having an adverse effect on outcome. The cost-effectiveness of CAP guidelines in an individual hospital depends on the systems that are available to identify patients with CAP and to measure the processes of care. There is good evidence that following the recommendations of the CAP guidelines does improve the cost-effectiveness of care and, therefore, that an audit of CAP may be worth the effort.

The excretion of ciprofloxacin in the small bowel was studied in 40 patients undergoing bowel surgery. Ciprofloxacin (200 mg) was administered iv, and intestinal samples were collected over a 120-min period. In ileal loops ciprofloxacin concentrations reached a peak of 4.0 mg/L, whereas in caecal fluid samples, concentrations were < 0.16 mg/L. Ciprofloxacin administered directly into the ileal and caecal loops did not result in measurable blood levels for 2 h. The results confirm that ciprofloxacin is selectively excreted into the small bowel.

Linezolid, the first oxazolidinone, is active against gram-positive bacteria, including multidrug-resistant strains. This multinational, randomized, double-blind, controlled trial compared the efficacy, safety, and tolerability of linezolid with vancomycin in the treatment of nosocomial pneumonia. A total of 203 patients received intravenous linezolid, 600 mg twice daily, plus aztreonam, and 193 patients received vancomycin, 1 g intravenously twice daily, plus aztreonam for 7-21 days. Clinical and microbiological outcomes were evaluated at test of cure 12-28 days after treatment. Clinical cure rates (71 [66.4%] of 107 for linezolid vs. 62 [68.1%] of 91 for vancomycin) and microbiological success rates (36 [67.9%] of 53 vs. 28 [71.8%] of 39, respectively) for evaluable patients were equivalent between treatment groups. Eradication rates of methicillin-resistant Staphylococcus aureus and safety evaluations were similar between treatment groups. Resistance to either treatment was not detected. Linezolid is a well-tolerated, effective treatment for adults with gram-positive nosocomial pneumonia.

We compared ceftazidime monotherapy with ceftriaxone/tobramycin in a prospective, randomized clinical trial that included 580 patients with serious hospital-acquired infections. One-half of the patients had an underlying disease with a rapidly or ultimately fatal prognosis; 40% were nursed in intensive care units. Clinical response among patients with pneumonia (73% in the ceftazidime group vs. 65% in the ceftriaxone/tobramycin group), septicemia (73% vs. 59%), and complicated urinary tract infections (80% vs. 76%) showed that there were no significant differences in efficacy between the two regimens. Pseudomonas aeruginosa was the most prevalent pathogen and was effectively eradicated by both treatments. The odds of bacteriologic cure with either study regimen were equal. Mortality was similar in both treatment groups. Ceftazidime monotherapy was not associated with a higher incidence of development of resistance or superinfection. Both regimens were well tolerated; no patients receiving ceftazidime evidenced nephrotoxicity, compared with nine who received the combination. We conclude that ceftazidime may be used as monotherapy in the empirical treatment of patients with serious nosocomial infections.