Bacteremia Due to Coagulase-negative Staphylococci: Do We Know What it Means?
ABSTRACT & COMMENTARY
Source: Souvenir D, et al. Blood cultures positive for coagulase-negative staphylococci: Antisepsis, pseudobacteremia, and therapy of patients. J Clin Microbiol 1998;36:1923-1926.
This cohort study was conducted over 12 weeks in two tertiary-care teaching hospitals to determine the incidence of significant coagulase-negative staphylococcal bacteremia vs. that of so called "pseudobacteremia" i.e., contaminated blood cultures, and to evaluate drug therapy in patients whose blood cultures yielded coagulase-negative staphylococci. A total of 3276 cultures of blood from 1433 patients were evaluated in the study. Using published criteria, significance was assigned retrospectively to the results of blood cultures by a panel of infectious disease physicians who achieved 100% agreement with the attending physicians' intuitive clinical impressions when classifying significant bacteremia, the criteria for which were bacteremia accompanied by prolonged temperature ³ 38°C, hypotension, leukocytosis or neutropenia with a left-shift differential, or disseminated intravascular coagulation in immunosuppressed patients managed with intravascular devices, peritoneal dialysis, or hemodialysis and those in the ICU), 95% agreement in designating contamination was achieved using the following criteria: patients at low risk with an insignificant febrile episode, those whose sepsis was unequivocally caused by a known pathogen, clinical shock-like syndromes such as ARDS, or aspiration pneumonia for which coagulase-negative staphylococci infection was an unlikely cause. Thus, 89 (2.7%) cultures yielded skin flora, with 81 of 89 (91%) involving coagulase-negative staphylococci. Significant coagulase-negative staphylococcal bacteremia accounted for 20 of 81 (24.7%), indeterminate bacteremia for 10 of 81 (12.3%), and contamination for 59 of 81 (72.8%).
All patients with significant coagulase-negative staphylococcal bacteremia were treated as were five of 10 with indeterminate bacteremia and 24 of the 59 patients with contaminated blood cultures. Vancomycin was used to treat 18 (90%) of those with significant bacteremia and 20 (83%) of those with contaminated blood cultures, almost the same proportion. Although inappropriate, there were no significant adverse events or prolongation of hospital stays; however, due to the use of vancomycin, an extra $1000 per patient was spent.
Souvenir and associates noted that coagulase-negative staphylococci continue to be the most common cause of pseudobacteremia and, although recognized as such at the time, attending physicians nonetheless opted to treat empirically, usually with vancomycin, indicating that measures to limit the unnecessary use of vancomycin and other agents have yet to take effect.
COMMENT BY J. PETER DONNELLY, PhD
One would have thought that the advent of glycopeptide-resistant enterococci, the stern editorials and guidelines for controlling antibiotic usage, and the ensuing media coverage would have been enough to deter all but the foolhardy from using vancomycin empirically. But, this is apparently no so. It is true that this study was done in 1995 when glycopeptide intermediate resistant Staphylococcus aureus remained an awesome though a distant threat. Yet, these presumably sane and responsible physicians, knowing even then the evidence to the contrary, still felt compelled to treat half of the patients with indeterminate bacteremia and a third of those with pseudobacteremia with a course of antibiotics, mostly vancomycin. The investigators themselves believe this to have represented defensive medicine. They may be right, but here in Europe, where resort to litigation is still very much the exception, I doubt if physicians attending the same sorts of patients would have behaved any differently. The culture of empirical antibiotic therapy is just as pervasive and as perplexing here as elsewhere. Frankly ill patients and even potentially ill immunocompromised patients are being treated empirically until the offending bacterial isolate is proven innocent of the charge of being a pathogen. Yet, everyone knows that recovering coagulase-negative staphylococci from blood cultures is most likely to represent catheter colonisation if a device is present or contamination if one is not, even in the most vulnerable of patients, and seldom heralds a fulminant infective disease. Indeed, the term coagu-lase-negative staphylococci embraces such a variety of different species and subtypes that one cannot be absolutely sure that two cultures ever yield identical strains and, even if the isolates appear identical, they may not be genetically present in the same blood culture and may present difficulty in accurately identifying individual species.
Quite apart from the near impossibility of proving innocence, it seems to me, at least in this age of evidence-based medicine, that the case for using a glycopeptide empirically to treat bacteremia due to coagulase-negative staphylococci, or other gram-positive cocci for that matter, has never been proven. Rather, the practice was established in the absence of evidence and now the burden of proof lies with those who disagree. Generally speaking, empirical use of antibiotics has, ironically, been made possible by their relative safety and their reputation of being "miracle drugs." Both are still true. Although not a physician, I have seen the evidence first-hand of the remarkable recovery that can occur when an antibiotic is used to treat a real bacterial infection. Also, despite the hype of competing pharmaceutical companies, antibiotics are still among the safest licensed drugs around and are well tolerated physically and emotionally by almost everyone.
So what has gone wrong? And, just as important, how can it be put right? Recently, the British House of Lords Science and Technology Committee published its seventh Report on "Resistance to Antibiotics and other Antimicrobial Agents." Their timing could not have been more impeccable and, being dedicated to their task, they made no fewer than 54 recommendations, beginning with "antibiotic resistance is a fact of life" and ending with the declaration that "action or inaction now, not only by Government but by everyone with a stake in public health will have a real impact on the public health legacy which we pass on to the next generation." With this, their lordships threw down the gauntlet. It is up to us "stakeholders" to accept their noble challenge.
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