Duration of Therapy
The ideal length of antibiotic therapy is still under debate. In a prospective randomized clinical
trial, Chastre et al. (291) demonstrated that an 8-day antibiotic regimen is comparable to a
15-day regimen in terms of mortality, superinfections, and VAP recurrence. A seven-day
treatment course was described as safe, effective, and less likely to promote the growth of
resistant organisms in patients who are clinically improving. Patients with VAP caused by
non-fermenting gram-negative bacilli, includingP. aeruginosa,given 8 days of antimicrobial
therapy had no less favorable outcomes, but had a higher infection-recurrence rate compared
with those receiving 15 days of treatment (40.6%vs.25.4%; difference, 15.2%, 90% CI, 2.9 to
26.6). This was not found in patients with VAP caused by MRSA, in whom infection recurrence
was 14.3% and 19% for the 8- and 15-day courses of antibiotics, respectively (90% CI, -9.9 to
0.4). Most authors agree, nevertheless, that the length of treatment should be tailored to suit
each patient (264).
Resolution patterns can help optimize the duration of antibiotic therapy. Thus, after 48 to
72 hours of defervescence (apyrexia) and resolution of hypoxemia, antibiotic therapy can be
withdrawn (56). In patients with ARDS, fever is the main clinical variable used to evaluate the
response to therapy.
Examining the Causes of Treatment Failure
Treatment failure should be assessed to simultaneously determine both the pulmonary/
extrapulmonary and infectious/non-infectious causes of a failed response. The etiology of
treatment failure can be ascribed to three possible causes: (a) inadequate antibiotic treatment,
(b) concomitant foci of infection, or (c) a noninfectious origin of disease (292). In a study
designed to establish the causes of nonresponse to treatment in VAP patients in an ICU
performed by Ioanas et al. (293), of a total of 71 patients, 44 (62%) were described as
nonresponders. In 64% of these nonresponders, at least one cause of nonresponse was
identified: inappropriate treatment (23%), superinfection (14%), concomitant foci of infection
(27%), and noninfectious origin (16%). The remaining nonresponding patients experienced
septic shock or multiple organ dysfunction or had acute respiratory distress syndrome. In this
type of situation, we would recommend the following: when there is clinical worsening and a
positive culture result, antimicrobial treatment should be adjusted and resistance assessed;
further respiratory sampling should be undertaken, using invasive techniques; central lines
should be checked and removed, if necessary, and surveillance cultures taken (294); urine
cultures; echocardiography; and ultrasonographic examination of the abdomen. Further
possible examinations include CT scans of the sinuses, chest CT (to check for pulmonary
embolism or abscess and empyema formation), and abdominal CT.
REFERENCES
- Niederman MS. Guidelines for the management of respiratory infection: why do we need them, how
should they be developed, and can they be useful? Curr Opin Pulm Med 1996; 2(3):161–165. - Tablan OC, Anderson LJ, Besser R, et al. Guidelines for preventing health-care–associated
pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices
Advisory Committee. MMWR Recomm Rep 2004; 53(RR-3):1–36. - Vincent JL, Bihari DJ, Suter PM, et al. The prevalence of nosocomial infection in intensive care units
in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC
International Advisory Committee. JAMA 1995; 274(8):639–644. - Richards MJ, Edwards JR, Culver DH, et al. Nosocomial infections in medical intensive care units in
the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999; 27(5):
887–892. - Bouza E, Perez A, Munoz P, et al. Ventilator-associated pneumonia after heart surgery: a prospective
analysis and the value of surveillance. Crit Care Med 2003; 31(7):1964–1970. - Santucci SG, Gobara S, Santos CR, et al. Infections in a burn intensive care unit: experience of seven
years. J Hosp Infect 2003; 53(1):6–13. - Abramczyk ML, Carvalho WB, Carvalho ES, et al. Nosocomial infection in a pediatric intensive care
unit in a developing country. Braz J Infect Dis 2003; 7(6):375–380.
196 Bouza and Burillo