Adhering to the current guideline recommendations for the treatment of intensive-care patients at risk of infection with multi-drug resistant (MDR) pneumonia might be associated with an increased risk of death. The findings, published in an Article Online First in The Lancet Infectious Diseases, highlight the need for The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) guidelines to be reassessed.
The current ATS-IDSA guidelines for the management of hospital-acquired, ventilator-associated, and health-care associated pneumonias recommend prompt empirical antibiotic treatment (before the culture results are known) of patients at risk of multi-resistant infection. According to the guidelines, these patients should be given a triple regimen of antibiotics—a combination of two drugs against Gram-negative pathogens and one against meticillin-resistant Staphlococcus aureus (MRSA)—so that at least one drug is active against any likely infectious agent. However, since the publication of the guidelines in 2005, several studies have failed to a show a benefit of dual Gram-negative therapy over monotherapy.
The Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) study was a performance improvement project designed to validate the current ATS-IDSA guidelines and assess the observance of the treatment recommendations and outcomes of patients at risk for MDR pneumonia.
303 patients at risk of MDR pneumonia were enrolled from four academic centres across the USA. 129 patients were given guideline-compliant antibiotic treatment, and 174 patients received non-compliant treatment.* In these patients at risk for MDR infections, the Kaplan-Meier estimate of survival to 28 days was 65% in the compliant group and 79% in the non-compliant group. The difference in survival remained after adjustment for severity of illness.
The authors say: "Our results further question the need for combination Gram-negative empirical treatment for patients with pneumonia, even those who are severely ill and at risk of multi-drug resistant pathogens."
They conclude: "[We] recommend that the planned, revised ATS-IDSA guidelines be reassessed before widespread implementation. Since the most common reason for non-compliance was failure to use a secondary anti-Gram-negative drug, we suggest a comparison of regimens employing MRSA treatment and single versus dual Gram-negative coverage."
In a Comment, Santiago Ewig from the Center for Thoracic Diseases of the Ruhrgebiet, Bochum, Germany, questions the validity of the findings, but points out that the recommended triple approach is not supported by the available evidence and is not necessarily correct: "All patients with septic shock, and probably severe sepsis, should receive dual coverage or triple coverage if MRSA is indicated. Whether all haemodynamically stable patients with nosocomial pneumonia need such a wide coverage is questionable; at least, de-escalation [ie, monotherapy] treatment is mandatory, since it reduces selection pressure, organ toxic effects, and saves money. After all, de-escalation is what matters. The definition of non-adherence to American Thoracic Society guidelines should not read 'less than triple therapy' but rather 'less than long-term prognosis and risk-adjusted broad coverage and de-escalation according to culture and susceptibility results'."
Professor Daniel Kett, the Miller School of Medicine at the University of Miami, Miami, Florida, USA. T) +1 (305) 585 6664 E) dkett@med.miami.edu
Dr Santiago Ewig, Center for Thoracic Diseases of the Ruhrgebiet, Bochum, Germany. E) ewig@augusta-bochum.de
For full Article and Comment see: http://press.thelancet.com/tlidpneumonia.pdf
Notes to Editors: *Non-compliance included failure to use a second anti-Gram-negative drug (154 patients) and failure to use either a primary anti-Gram-negative drug (24 patients) or an anti-MRSA drug (24 patients).
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The Lancet Infectious Diseases