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. 1998 Nov 28;317(7171):1526.

Effectiveness of antibiotic prophylaxis in critically ill patients

Distinction must be made between tracheal inflammation and pneumonia

P J Sanderson 1
PMCID: PMC1114357  PMID: 9831599

Editor—It is ironic that D’Amico et al’s meta-analysis of trials of antibiotic prophylaxis for respiratory infection1 appears in the same issue as the House of Lords’ report on resistance to antibiotic drugs.2 D’Amico et al did not restrict diagnostic criteria and did not distinguish between tracheobronchitis and pneumonia in their analysis. Although this distinction can be difficult, it is worth recognising that colonisation of the trachea and tracheobronchitis are common but trivial events in intubated patients and are probably inevitable. Whether their prevention is worth while is doubtful.

It would be interesting to know the comparative prevalence of tracheobronchitis in the 16% of treated and 36% of control patients who had “respiratory infection” in the trials that D’Amico et al studied. Inappropriate prophylaxis contributes to the overuse of antibiotics. We should remain cautious about topical and systemic prophylaxis for respiratory infection in critically ill patients and continue to try to separate true lung infection from tracheal inflammation.

References

  • 1.D’Amico R, Pifferi S, Leonetti C, Torri V, Tinazzi A, Liberati A. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ. 1998;316:1275–1285. doi: 10.1136/bmj.316.7140.1275. . (25 April.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Abbasi K. Report calls for action on antibiotic resistance. BMJ. 1998;316:1261. doi: 10.1136/bmj.316.7140.1261. . (25 April.) [DOI] [PubMed] [Google Scholar]
BMJ. 1998 Nov 28;317(7171):1526.

Selective decontamination offers no advantage

B Allaouchiche 1, H Jaumain 1, D Chassard 1

Editor—Our first comment on the study by D’Amico et al concerns the search through Medline.1-1 They have excluded a study by Godard et al, who conducted a double blind placebo controlled trial to test the efficacy of prevention of nosocomial infections by selective decontamination.1-2 Selective decontamination reduced the proportion of hospital acquired infections (33% v 60%, P=0.02) and the number of cases of pneumonia (2 v 13 cases, P<0.01). Selective decontamination alone, however, failed to reduce the proportion of infected patients (26% v 34.5%, P=0.20), mean duration of stay in hospital, and mortality.

The diagnosis of nosocomial pneumonia remains a source of considerable debate. For Gastinne et al, bacteriological documentation was not required (clinical approach).1-3 Other authors have used invasive procedures, but the lack of reliability of these techniques in the diagnosis of nosocomial pneumonia has recently been reported.1-4

Our last comment concerns the existence of bacterial samples that yield false negative results. Gastinne et al showed that 82% of tracheal aspirates contained detectable concentrations of antibiotics, which suggests that the microbiological criteria used to assess pneumonia may be unreliable.1-5 In the light of these methodological problems it seems difficult to report a potential advantage of selective decontamination to prevent pneumonia in critically ill patients.

References

  • 1-1.D’Amico R, Pifferi S, Leonetti C, Torri V, Tinazzi A, Liberati A. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ. 1998;316:1275–1285. doi: 10.1136/bmj.316.7140.1275. . (25 April.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-2.Godard J, Guillaume C, Reverdy ME, Bachmann P, Bui-Xuan B, Nageotte A, et al. Intestinal decontamination in a polyvalent ICU. A double-blind study. Intensive Care Med. 1990;16:307–311. doi: 10.1007/BF01706355. [DOI] [PubMed] [Google Scholar]
  • 1-3.Gastinne H, Wolff M, Delatour F, Faurisson F, Chevret S. A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. The French Study Group on Selective Decontamination of the Digestive Tract. N Engl J Med. 1992;326:594–599. doi: 10.1056/NEJM199202273260903. [DOI] [PubMed] [Google Scholar]
  • 1-4.Papazian L, Thomas P, Garbe L, Guignon I, Thirion X, Charrel J, et al. Bronchoscopic or blind sampling techniques for the diagnosis of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1995;152:1982–1991. doi: 10.1164/ajrccm.152.6.8520766. [DOI] [PubMed] [Google Scholar]
  • 1-5.Gastinne H, Wolff M, Lachatre G, Boiteau R, Savy FP. Antibiotic levels in bronchial tree and in serum during selective digestive decontamination. Intensive Care Med. 1991;17:215–218. doi: 10.1007/BF01709880. [DOI] [PubMed] [Google Scholar]
BMJ. 1998 Nov 28;317(7171):1526.

Antibiotic prophylaxis can lead to contamination with Clostridium difficile

Daryl Leung 1

Editor—D’Amico et al suggested, on the basis of a systematic meta-analysis, that prophylactic topical and systemic antibiotics (cefotaxime) should be used to prevent pneumonia associated with ventilation.2-1 The rationale did not seem to consider complications, morbidity, or mortality in other patients in the ward or hospital, who might, as a result, develop the antibiotic induced complication of infection with Clostridium difficile. Such nosocomial infection can be lethal.

Contamination of the intensive care unit and hospital with C difficile is another problem that D’Amico et al have not taken into consideration. Overuse of cefotaxime has been specifically implicated as a cause of such outbreaks.2-2 The mechanism of spread by contamination of the environment with spores2-3 may be too high a price to pay in terms of morbidity, mortality, and cost benefit analysis. It can lead to ward closures and postponement of routine procedures and operations as a result of nosocomial infection

References

  • 2-1.D’Amico R, Pifferi S, Leonetti C, Torri V, Tinazzi A, Liberati A. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ. 1998;316:1275–1285. doi: 10.1136/bmj.316.7140.1275. . (25 April.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2-2.Starr JM, Rogers TR, Impallomeni M. Hospital-acquired Clostridium difficile diarrhoea and herd immunity. Lancet. 1997;349:126–128. doi: 10.1016/S0140-6736(97)80053-0. [DOI] [PubMed] [Google Scholar]
  • 2-3.Leung DL. Hospital-acquired Clostridium difficile diarrhoea. Lancet. 1998;349:1177. doi: 10.1016/s0140-6736(05)63056-5. [DOI] [PubMed] [Google Scholar]
BMJ. 1998 Nov 28;317(7171):1526.

Authors’ reply

Roberto D’Amico 1,2,3, Silvia Pifferi 1,2,3, Alessandro Liberati 1,2,3

Editor—Unlike Sanderson, we find it interesting rather than ironic that our review was in the same issue of the House of Lords’ report that was aimed at stimulating critical thinking against generalised fears of antimicrobial resistance. Critically ill patients undergoing ventilation are at high risk of pneumonia and death, and the issue whether or not they should be routinely treated with antimicrobials deserves great attention.

We accessed data on individual patients, which allowed us to ascertain that most patients in all trials were treated with antimicrobials at some point during their stay in an intensive care unit, regardless of the initial policy of the unit. The question is thus no longer whether, but rather when, they should be treated—immediately, as a policy, or only once their infection becomes clinically evident.

Sanderson states that tracheobronchitis is a trivial event for patients, which we disagree with. We checked the proportion of patients with pneumonia in our trials. In studies in which a topical and systemic combination was used, 10 out of 15 trials (1895 out of 2698 patients) considered only pneumonia: the proportion of patients with pneumonia was higher among the controls (32% v 13%). This is consistent with data from a previous meta-analysis, which showed that pneumonia was more frequent in the controls.3-1

Allaouchiche et al believe that Godard et al’s study should have been included in our review.3-2 We excluded it because it was not randomised. The two participating wards contributed to the study during two consecutive periods.

Diagnosis of nosocomial pneumonia remains a source of debate. In a previous paper we showed a similar reduction in the odds of infections, no matter whether or not a protected or distal technique or bronchoalveolar lavage was used or not to diagnose pneumonia (odds ratio 0.38 (95% confidence interval 0.29 to 0.49) v 0.36 (0.29 to 0.44) respectively).3-3

Leung warns about the danger of infection with Clostridium difficile. This is caused by overgrowth of C difficile after long term use of systemic antibiotics. Topical prophylaxis as selective decontamination of the digestive tract usually does not include the type of new antimicrobials that work against the normal flora, and as these are excreted via bile and mucus into the gut they may induce C difficile. Moreover, the most used systemic prophylaxis—cefotaxime treatment for a few days—has a minimal impact on resistance to colonisation.3-4 These observations seem to support our view that no trial showed a clinically significant harmful effect of selective decontamination of the digestive tract. These answers should help readers to distinguish between what is evidence based and what is still largely “opinion based.”

References

  • 3-1.Heyland DK, Cook DJ, Jeascher R, Griffith I, Lee HN, Guyatt GH. Selective decontamination of the digestive tract: an overview. Chest. 1994;105:1221–1229. doi: 10.1378/chest.105.4.1221. [DOI] [PubMed] [Google Scholar]
  • 3-2.Godard J, Guillaume C, Reverdy ME, Bachmann P, Bui-Xuan B, Nageotte A, et al. Intestinal decontamination in a polyvalent ICU. A double-blind study. Intensive Care Med. 1990;16:307–311. doi: 10.1007/BF01706355. [DOI] [PubMed] [Google Scholar]
  • 3-3.Selective Decontamination of the Digestive Tract Trialists’ Collaborative Group. Meta-analysis of randomised controlled trials on selective decontamination of the digestive tract. BMJ. 1993;307:525–532. doi: 10.1136/bmj.307.6903.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3-4.Vollaard EJ, Cleasener HAL, Janssen AJHM. Influence of cefotaxime on microbial resistance in healthy volunteers. J Antimicrob Chemother. 1990;26:117–123. doi: 10.1093/jac/26.1.117. [DOI] [PubMed] [Google Scholar]

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