No Difference in Mortality
Although secondary infections were more common with short courses, there was no difference in mortality. This difference was explained by the fact that since patients were followed for 21 days, the 8-day group had more time to develop a secondary infection because they were off antibiotics more than twice as long as the 15- day group.8
Patients were not followed after the 21-day period to evaluate for further resistant infections associated with antibiotic use, such as C. difficile
infection. A finding that was not surprising in both studies was that there were more antibiotic-free days in the short-course groups, taking into account antibiotics used for the treatment of secondary infections.7,8
In these 2 studies, a shorter-course of antibiotics did not negatively impact patient outcomes or mortality. In fact, there was the added benefit of less overall antibiotic exposure and although patients were not assessed for the development of a C. difficile
infection, presumably this should decrease the risk of infection.
There have been other attempts to shorten antibiotic therapy that do not fall into the prospective, randomized studies included above. Using objective measures to guide antibiotic duration instead of arbitrarily deciding treatment durations would be optimal for clinicians to individualize treatment based on the stability of the patient, resulting in earlier antibiotic discontinuation for many patients. One study used clinical pulmonary infection scores (CPIS) in patients with radiographic findings suggestive of nosocomial pneumonia to stratify patients at low risk of complications due to short courses of antibiotics. In this study, patients with a low CPIS were randomized to receive either ciprofloxacin for 3 days or standard care (antibiotics for 10-21 days). More severely ill patients were excluded. Clinical outcomes were similar between the 2 groups. As can be expected, in the short-course group, there were significantly more antibiotic-free days, and in the long-course group, there was more resistance and/or super-infections.9
This study was performed in 2000 and is now dated, but the principle is still relevant.
In suspected VAP, using ventilator settings as a surrogate for degree of illness may also be a method to transition patients off empiric antibiotics earlier. In a retrospective study, patients with stable and minimal ventilator settings empirically treated for suspected VAP who received less than 3 days of antibiotics had similar duration of mechanical ventilation, mortality, and time to discharge compared with a longer-duration group (greater than 3 days). However, the majority of patients in this study most likely did not truly have VAP, and therefore this strategy should be used only for stable patients for whom the diagnosis of VAP is uncertain.10
Biomarkers such as procalcitonin have also been of interest as a marker to guide antimicrobial duration. There is no clear consensus on the use of procalcitonin to diagnose bacterial infections and data conflicts on whether strategies that utilize this biomarker successfully result in shorter antibiotic durations. A metaanalysis of 14 studies including 4211 patients with acute respiratory infections found that overall, the duration of antibiotics was shorter in the procalcitonin-guided group (7 days vs 10 days; P <.0001). Treatment duration was also shorter in the subset of patients with VAP (11 days vs 14 days; P = .02). Although procalcitonin may have the potential to help guide antimicrobial decisions in HAP/ VAP, these durations of therapy are longer than recommended. It is unclear whether procalcitonin is as useful for antibiotic decision making at earlier time points.11
Shortening antimicrobial duration and thereby reducing overall antibiotic exposure is an effective antimicrobial stewardship strategy to slow the emergence of resistance. Current IDSA HAP/VAP guidelines support short-course treatment regardless of the organism and instead favor individualizing treatment and extending therapy when needed based on imaging and/or clinical findings.12
Overall, shorter-treatment durations are associated with more antibiotic-free days and fewer MDR secondary or recurrent infections and do not negatively affect clinical outcomes.3
In this era of antibiotic resistance, reducing overall antibiotic exposure may be a more easily implemented than programs focused on preventing broad-spectrum antibiotic use.
Dr. Hanretty is a clinical pharmacist in infectious diseases at St. Christopher’s Hospital for Children in Philadelphia, Pennsylvania. She completed a PGY1 Pharmacy Residency at UCSF Medical Center in San Francisco, and a PGY2 Residency in Infectious Diseases Pharmacy at Temple University. She is an active member of SIDP.
Dr. Gallagher is a clinical professor at Temple University School of Pharmacy and clinical pharmacy specialist in infectious diseases at Temple University Hospital, both in Philadelphia. He also is the director of the PGY2 Residency in Infectious Diseases Pharmacy at Temple. He is an active member of SIDP.
- Tabah A, Cotta MO, Garnacho-Montero J, et al. A systematic review of the definitions, determinants, and clinical outcomes of antimicrobial de-escalation in the intensive care unit. Clin Infect Dis. 2016;62(8):1009-1017. doi: 10.1093/cid/civ1199.
- Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis. 2001;1(2):101-114. doi: 10.1016/S1473-3099(01)00066-4.
- Pugh R, Grant C, Cooke RP, et al. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2015;(8):CD007577. doi: 10.1002/14651858.CD007577.pub3.
- Magill SS, Edwards JR, Fridkin SK, et al. Survey of health care–associated infections. N Engl J Med. 2014;370(26):2542-2543. doi: 10.1056/NEJMc1405194.
- Kollef MH, Hamilton CW, Ernst FR. Economic impact of ventilator-associated pneumonia in a large matched cohort. Infect Control Hosp Epidemiol. 2012;33(3):250-256. doi: 10.1086/664049.
- Society AT, America IDSo. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416. doi:10.1164/rccm.200405-644ST.
- Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588-2598. doi: 10.1001/jama.290.19.2588.
- Capellier G, Mockly H, Charpentier C, et al. Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment. PLoS One. 2012;7(8):e41290. doi: 10.1371/journal.pone.0041290.
- Singh N, Rogers P, Atwood CW, et al. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 2000;162(2 Pt 1):505-511. doi: 10.1164/ajrccm.162.2.9909095.
- Klompas M, Li L, Menchaca JT, et al. Ultra-short-course antibiotics for patients with suspected ventilator-associated pneumonia but minimal and stable ventilator settings. Clin Infect Dis. 2016; 64(7):870-876. doi: 10.1093/cid/ciw870.
- Schuetz P, Briel M, Christ-Crain M, et al. Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis. Clin Infect Dis. 2012;55(5):651-662. doi: 10.1093/cid/cis464.
- Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111. doi: 10.1093/cid/ciw353.