Prophylactic Antibiotics Lower Bacterial Resistance in ICU

 CME/CE

News Author: Laurie Barclay, MD
CME Author: Charles P. Vega, MD

CME/CE Released: 03/29/2011 ; Valid for credit through 03/29/2012

March 29, 2011 — Preventive antibiotic use significantly lowers the risk for infection with antibiotic-resistant bacteria in patients in the intensive care unit (ICU), according to the results of an open-label, clustered group-randomized, crossover study reported online first March 21 in The Lancet Infectious Diseases.

"Previously, we assessed selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) on survival and prevention of bacteraemia in patients in intensive-care units," write Anne Marie G. A. de Smet, MD, from University Medical Center in Utrecht , the Netherlands , and colleagues. "In this analysis, we aimed to assess effectiveness of these interventions for prevention of respiratory tract colonisation and bacteraemia with highly resistant microorganisms acquired in intensive-care units."

Between May 2004 and July 2006, participants admitted to 13 ICUs in the Netherlands with an expected duration of mechanical ventilation of more than 48 hours or an expected duration of stay of more than 72 hours were randomly assigned to receive SOD, SDD, or standard care. SOD consisted of topical tobramycin, colistin, and amphotericin B in the oropharynx, and SDD consisted of SOD antibiotics in the oropharynx and stomach plus 4 days of intravenous cefotaxime.

An independent clinical pharmacist blinded to ICU identity applied the computer-randomized order of study regimens. To assess acquired infection among patients with ICU stay of more than 3 days, the investigators calculated crude odds ratios (ORs) for rates of bacteremia or respiratory tract colonization with highly resistant microorganisms.

Of 5939 eligible patients, 5927 (> 99%) had available data, and 5463 (92%) were in the ICU for more than 3 days. Bacteremia developed after 3 days in 239 (13%) of 1837 patients in standard care, 158 (9%) of 1758 patients in SOD (OR, 0.66; 95% confidence interval [CI], 0.53 - 0.82), and 124 (7%) of 1868 patients in SDD (OR, 0.48; 95% CI, 0.38 - 0.60). Bacteremia with highly resistant microorganisms developed in 8 patients during SDD vs 18 patients (with 19 episodes) during standard care (OR, 0.41; 95% CI, 0.18 - 0.94; rate reduction [RR], 59%; absolute risk reduction [ARR], 0.6%) and 20 patients during SOD (OR, 0.37; 95% CI, 0.16 - 0.85; RR, 63%; ARR, 0.7%).

Endotracheal aspirate cultures were obtained in approximately half of the patients staying in ICUs for more than 3 days: 881 (49%) receiving standard care, 886 (50%) receiving SOD, and 828 (44%) receiving SDD.

Respiratory tract colonization with highly resistant microorganisms occurred in 128 (15%) of patients during standard care, in 74 (8%) during SDD (OR, 0.58; 95% CI, 0.43 - 0.78; RR, 38%; ARR, 5.5%), and in 88 (10%) during SOD (OR, 0.65; 95% CI, 0.49 - 0.87; RR, 32%; ARR, 4.6%). The lowest rates of acquired respiratory tract colonization with gram-negative bacteria or cefotaxime-resistant and colistin-resistant pathogens occurred during SDD.

"The beneficial effects of SDD and SOD on outcomes, together with the favourable results for infection and colonisation with antibiotic-resistant pathogens reported in this study, justify the extended use of these interventions in settings with low rates of antibiotic resistance," the study authors write.

Study Limitations

Limitations of this study include slight differences in the baseline characteristics among the study groups, suggesting that patients receiving SDD or SOD were more severely ill than were those receiving standard care. In addition, surveillance of digestive tract colonization was done only in the SDD group, and respiratory tract samples were obtained twice every week during SDD and SOD but not during standard care.

"The benefits of prophylactic antibiotic use need to be balanced against the inevitable risks of selection of antibiotic-resistant bacteria," the study authors conclude. "As such, widespread use of topical antimicrobial prophylaxis in patients in intensive-care units has been the subject of debate for years."

In an accompanying comment, Jean-Louis Vincent and Frédérique Jacobs, from Erasme Hospital in Brussels , Belgium , further discuss the study limitations.

"In summary, the interesting findings are mitigated by a lack of effect on problematic organisms, the study setting, and the length of observation," Drs. Vincent and Jacobs write. "We believe that the data provided by our Dutch colleagues will not convince the world to use SDD or SOD."

This study received no external funding. Two of the study authors have disclosed various financial relationships with 3M, Destiny Pharma, Cepheid, Phico Therapeutics, Pfizer, Aventis, Novartis, and/or Kimberly Clark. The other study authors have disclosed no relevant financial relationships. Drs. Vincent and Jacobs have disclosed no relevant financial relationships.

Lancet Infect Dis. Published online March 21, 2011. Abstract

The Infectious Diseases Society of America provides a number of guidelines for the prevention of infection in the acute care setting on its Web site.

Clinical Context

SDD and SOD can improve mortality outcomes among patients in the ICU, according to a previous study by the authors of the current research. This study, which was published in the January 1, 2009, issue of the New England Journal of Medicine, did not demonstrate a significant difference in the gross mortality rates in comparing participants receiving usual care, SDD, or SOD. However, on adjusted analyses, the ORs for death associated with the use of both SDD and SOD were significantly reduced vs usual care (0.83 and 0.86, respectively).

An important concern regarding the use of SDD and SOD is the emergence of resistant organisms. The current study addresses this issue.

Study Highlights

• The study used an open-label, clustered group-randomized controlled crossover design. It was conducted in 13 ICUs between 2004 and 2006.


• Patients eligible for study participation were expected to require mechanical ventilation for at least 48 hours or have an expected ICU stay of at least 72 hours.


• Participants were randomly selected to receive SDD, SOD, or usual care. SDD consisted of 4 days of intravenous cefotaxime plus topical application of an oral paste of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of application of the oral paste only.


• Patients receiving SDD and SOD were tested with oropharyngeal swabs to analyze bacterial colonization and antimicrobial resistance on admission and twice per week. Patients receiving SDD also had surveillance cultures of endotracheal aspirates performed twice weekly. All participants received blood cultures as part of the study protocol.


• The main study outcome was the effect of SDD and SOD vs usual care on rates of bacterial colonization of endotracheal aspirates, antimicrobial resistance, and rates of bacteremia.


• 5927 patients had data for study analysis. Patients receiving SDD and SOD were more seriously ill vs patients receiving usual care.


• The rates of bacteremia were 13%, 9%, and 7% in the usual care, SOD, and SDD groups, respectively. These differences yielded ORs of 0.66 (95% CI, 0.53 - 0.82) for SOD and 0.48 (95% CI, 0.38 - 0.60) for SDD.


• Researchers obtained 19,404 microbiological cultures from endotracheal aspirates. The rate of cultures was approximately 30% lower in the usual care group vs the SOD and SDD groups.


• Rates of endotracheal colonization with nonfermenting gram-negative rods, such as Pseudomonas aeruginosa and Acinetobacter spp, were similar in the SOD and SDD groups. However, colonization with Enterobacteriaceae was more common with SOD vs SDD.


• Colonization with enterococci occurred more frequently among participants receiving SDD vs SOD and usual care.


• Overall, the rates of respiratory tract colonization with highly resistant organisms were 15%, 10%, and 8% in the usual care, SOD, and SDD groups, respectively. These differences yielded ORs of 0.65 (95% CI, 0.49 - 0.87) for SOD and 0.58 (95% CI, 0.43 - 0.78) for SDD. Gram-negative bacteria accounted for 98% of all highly resistant microorganisms.


• Rates of resistance to the specific antibiotics used in SOD and SDD did not exceed 3%.

Clinical Implications

• Both SDD and SOD were associated with significant decreases in the risk for death vs usual care in a previous study of patients in ICU.


• In the current study, SOD and SDD among patients in ICU reduced the risk for bacteremia and also the risk for acquisition of highly resistant microorganisms on endotracheal aspirates.