These updated guidelines replace the previous management guidelines published in 2001. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.

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Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America

The influence of natural products upon drug discovery.

The use of antibiotics in food animals selects for bacteria resistant to antibiotics used in humans, and these might spread via the food to humans and cause human infection, hence the banning of growth-promoters. The actual danger seems small, and there might be disadvantages to human and to animal health. The low dosages used for growth promotion are an unquantified hazard. Although some antibiotics are used both in animals and humans, most of the resistance problem in humans has arisen from human use. Resistance can be selected in food animals, and resistant bacteria can contaminate animal-derived food, but adequate cooking destroys them. How often they colonize the human gut, and transfer resistance genes is not known. In zoonotic salmonellosis, resistance may arise in animals or humans, but human cross-infection is common. The case of campylobacter infection is less clear. The normal human faecal flora can contain resistant enterococci, but indistinguishable strains in animals and man are uncommon, possibly because most animal enterococci do not establish themselves in the human intestine. There is no correlation between the carriage of resistant enterococci of possible animal origin and human infection with resistant strains. Commensal Escherichia coli also exhibits host-animal preferences. Anti-Gram-positive growth promoters would be expected to have little effect on most Gram-negative organisms. Even if resistant pathogens do reach man, the clinical consequences of resistance may be small. The application of the 'precautionary principle' is a non-scientific approach that assumes that risk assessments will be carried out.

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Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data

Enterococci are best known as antibiotic-resistant opportunistic pathogens that are commonly recovered from patients who have received multiple courses of antibiotics and have been hospitalized for prolonged periods.1–6 These organisms were well established as a cause of endocarditis and urinary tract infections by the early 1900s,3 and members of the species Enterococcus faecalis were known to be a common cause of nosocomial infections by the early 1980s.3,7–9 The emergence of enterococci with resistance to vancomycin, seen predominantly in the species E. faecium, has been followed by an increase in the frequency with which this species is recovered. . . .

Vancomycin-resistant enterococcal infections

OBJECTIVE\nTo determine the excess length of stay, extra costs, and mortality attributable to nosocomial bloodstream infection in critically ill patients.\n\n\nDESIGN\nPairwise-matched (1:1) case-control study.\n\n\nSETTING\nSurgical intensive care unit (SICU) in a tertiary health care institution.\n\n\nPATIENTS\nAll patients admitted in the SICU between July 1, 1988, and June 30, 1990, were eligible. Cases were defined as patients with nosocomial bloodstream infection; controls were selected according to matching variables in a stepwise fashion.\n\n\nMETHODS\nMatching variables were primary diagnosis for admission, age, sex, length of stay before the day of infection in cases, and total number of discharge diagnoses. Matching was successful for 89% of the cohort; 86 matched case-control pairs were studied.\n\n\nMAIN OUTCOME MEASURES\nCrude and attributable mortality, excess length of hospital and SICU stay, and overall costs.\n\n\nRESULTS\nNosocomial bloodstream infection complicated 2.67 per 100 admissions to the SICU during the study period. The crude mortality rates from cases and controls were 50% and 15%, respectively (P < .01); thus, the estimated attributable mortality rate was 35% (95% confidence interval, 25% to 45%). The median length of hospital stay significantly differed between cases and controls (40 vs 26 days, respectively; P < .01). When only matched pairs who survived bloodstream infection were considered (n = 41), cases stayed in the hospital a median of 54 days vs 30 days for controls (P < .01), and cases stayed in the SICU a median of 15 days vs 7 days for controls (P < .01). Thus, extra hospital and SICU length of stay attributable to bloodstream infection was 24 and 8 days, respectively. Extra costs attributable to the infection averaged $40,000 per survivor.\n\n\nCONCLUSIONS\nThe attributable mortality from nosocomial bloodstream infection is high in critically ill patients. The infection is associated with a doubling of the SICU stay, an excess length of hospital stay of 24 days in survivors, and a significant economic burden.

Nosocomial Bloodstream Infection in Critically Ill Adults: Excess Length of Stay, Extra Costs, and Attributable Mortality

A progressive increase in the incidence of vancomycin resistance in strains of Enterococcus faecium (VREF) has severely constrained treatment options for patients with infection caused by this emerging pathogen. Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic, is active in vitro against VREF, with an MIC90 of 1.0 mg/L. We studied the clinical efficacy and safety of quinupristin/dalfopristin in the treatment of VREF infection. Two prospective studies were conducted simultaneously. The first enrolled only patients with VREF infection; the second included patients with infection caused by other gram-positive bacterial pathogens in addition to VREF. Patients were enrolled if they had signs and symptoms of active infection and no appropriate alternative antibiotic therapy. The recommended treatment regimen of quinupristin/dalfopristin was 7.5 mg/kg i.v. every 8 h for a duration judged appropriate by the investigator. A total of 396 patients with VREF infection were enrolled. The most frequent indications for treatment included intra-abdominal infection, bacteraemia of unknown origin, urinary tract infection, catheter-related bacteraemia, and skin and skin structure infection. This patient population had a high prevalence of severe underlying illness, including a history of diabetes mellitus, transplantation, mechanical ventilation, dialysis, chronic liver disease with cirrhosis and oncological disorders. The mean (+/- S.D.) duration of treatment was 14.5 +/- 10.7 days (range: 1-108). The majority of patients (82.1%) were treated every 8 h, as assessed on day 2 of treatment, while 15.9% were treated every 12 h. The clinical success rate was 73.6% [142/193 clinically evaluable patients; 95% confidence interval (CI): 67.4%, 79.8%], the bacteriological success rate 70.5% (110/156 bacteriologically evaluable patients; 95% CI: 63.4%, 77.7%) and the overall success (both clinical and bacteriological success) rate 65.8% (102/156 bacteriologically evaluable patients; 95% CI: 57.9%, 72.9%). VREF bacteraemia at entry, mechanical ventilation and laparotomy were associated with a worse outcome. Quinupristin/dalfopristin was generally well tolerated. The most common systemic adverse events related to treatment were arthralgias (9.1%) and myalgias (6.6%). Related laboratory abnormalities were infrequent. In these severely ill patients with VREF infection and no other clinically appropriate therapeutic alternatives, quinupristin/dalfopristin demonstrated substantial efficacy and a good nervous system, cardiovascular, gastrointestinal, renal and hepatic tolerability.

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The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium

Clinicians caring for patients with vancomycin-resistant Enterococcus faecium (VREF) infections face severe constraints in the selection of treatment. Quinupristin/dalfopristin (Synercid) is active in vitro against VREF, with a MIC(90) of 1.0 microg/mL. We investigated the clinical efficacy and safety of this agent in a multicenter, prospective, noncomparative, emergency-use study of 396 patients. Patients were included if they had signs and symptoms of active infection, including bacteremia of unknown origin, intra-abdominal infection, and skin and skin-structure infection, with no alternative antibiotic therapy available. The mean duration of treatment was 20 days (range, 4-40 days). The clinical response rate was 68.8% in the evaluable subset, and the overall response rate was 65.6%. The most common adverse events related to quinupristin/dalfopristin were arthralgias and myalgias. Related laboratory abnormalities were rare. In this severely ill patient population, quinupristin/dalfopristin was efficacious and demonstrated an acceptable safety profile in the treatment of VREF infection.

https://www.jstor.org/stable/info/4482899

F. Bompart

Papers

The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium

Treatment of vancomycin-resistant Enterococcus faecium infections with quinupristin/dalfopristin.