De-escalating MRSA Coverage in Nosocomial Pneumonia
Outcomes Associated With De-escalating Therapy for Methicillin-Resistant Staphylococcus aureus in Culture-Negative Nosocomial Pneumonia.
Cowley MC, Ritchie DJ, Hampton N, Kollef MH, Micek ST.
Chest. 2019 Jan;155(1):53-59. [Full text]
Although empirically covering patients with broad-spectrum antibiotics for nosocomial pneumonia is appropriate initially; however, it is unclear if and when antibiotics can be de-escalated, as pneumonia often is without culture data to guide therapy. This large retrospective study looked at the difference in outcomes in patients with nosocomial pneumonia with negative respiratory cultures that had anti-MRSA agents de-escalated and those that did not.
Patient population and Design
This single-center retrospective cohort study included adult patients admitted from 2012 to 2017 with nosocomial pneumonia and a negative respiratory culture.
All adult patients with an ICD-9/10 diagnosis of pneumonia were potentially eligible for inclusion. Those patients were subsequently screened to identify nosocomial pneumonia, defined as an index date of infection that was > 48 h after hospital admission, with a consistent chest x-ray, and at least one sign of infection: leukocytosis > 10 × 109 cells/L, leukopenia ≤ 4 × 109 cells/L, or fever ≥ 38.0° C. Patients with cystic fibrosis, lung transplant, or any malignancy were excluded.
In addition, patients had to have a negative respiratory culture (BAL, sputum, or tracheal aspirate) obtained and an anti-MRSA agent (vancomycin, linezolid, and ceftaroline) started on that index date. De-escalation was considered if patients had an active order for an alternative agent by day 4 with discontinuation of the initial antibiotic. This led to two groups, whether the anti-MRSA agent was discontinued within 4 days (de-escalation group) or continued (no de-escalation group).
The primary outcome was 28-day mortality after index date. The 28-day mortality was confirmed via review of the health records and the Social Security Death Index. Secondary outcomes included treatment failure, defined as restarting the MRSA agent between 2 and 7 days after discontinuation, hospital mortality, total length of ICU and hospital stay, length of ICU and hospital stay after index date, and development of acute kidney injury.
Results
Of 1,898 patients with an ICD-9-CM or ICD-10-CM code for pneumonia, 279 patients were included, with 92 patients who had their anti-MRSA agent de-escalated by day 4, and 187 patients in whom de-escalation did not occur. 1,177 patients were excluded because of a lack of an index date, 428 were excluded for having a positive respiratory culture, seven patients died within 4 days, and seven patients had received a lung transplant. A slight majority of patients (56%) were determined to have ventilator associated pneumonia,
Though by design none of the included patients had positive respiratory cultures, but 13% had positive cultures at other sites, consistent with concomitant infections, most commonly in the blood. Most patients received an anti-pseudomonal agent (92%), and vancomycin was the most common anti-MRSA agent chosen (78%).
Baseline characteristics were nearly similar between groups, though there was more chronic kidney disease in the de-escalation group (43% vs 32%, respectively). There was no difference in the change of severity of illness from index date to day 4, as seen by the incidence of patients transferred to the ICU, intubated, and started on a vasopressor. Notably, patients who had their anti-MRSA agents de-escalated by day 4 were more likely to have their anti-pseudomonal agent de-escalated as well (61/84; 73% vs 38/174; 22%, respectively) vs patients whose anti-MRSA agent was not de-escalated. Patients who were in the de-escalation group had 5 fewer days of anti-MRSA therapy than patients who were not de-escalated.
The primary end point of 28-day mortality was not different between the groups (de-escalation: 23% vs no de-escalation: 28%; △−5.5; 95% CI, −16.1 to 6.5; Kaplan-Meier survival curve log-rank P = 0.389) There was a difference in ICU and hospital length of stay after index date, with patients who were de-escalated being transferred out of the ICU 3 days earlier and discharged from the hospital 5 days earlier. There was no difference in treatment failure between the groups. Patients who had their anti-MRSA agent de-escalated had a lower incidence of AKI (29/80; 36% vs 85/170; 50%; △−13.8%; 95% CI, −26.9 to −0.4)
Discussion
In this retrospective of patients with nosocomial pneumonia with a negative respiratory culture, de-escalation of the anti-MRSA agent showed no difference in 28 day mortality, shorter ICU and overall length of stay, and a lower incidence of AKI. A typical limitation of retrospective studies is that it is unclear if clinical criteria led to the de-escalation, i.e. improvement, with this population being compared to a population that is not improving or worsening. The authors argued against this as the patient populations were well matched at baseline in terms of level of illness and co-morbidities. They considered the length of stay potentially longer potentially from extending IV antibiotics or because of the resulting AKI.
Regardless, de-escalation when possible is always the aspiration. Another strategy for de-escalation is MRSA nares screening. In one retrospective of 561,325 cultures from a variety of anatomical sites, the NPV of for ruling out MRSA infection was 96.5% [2]. Procalcitonin (PCT) for de-escalation has also been studied but is more controversial and the IDSA/ATS guidelines recommend against the use of PCT [1]. Based on the available evidence, a combination of clinical improvement, a negative respiratory culture (as in this study), and/or a negative MRSA nares culture seem to support de-escalation.
| F: Follow up | N/A |
| R: Randomization | N/A |
| I: Intention to treat | N/A |
| S: Similar at baseline | N/A |
| B: Blinding | N/A |
| E: Equal treatment | N/A |
| S: Source (funding) | None |
- 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 Sep 1;63(5):e61-e111.
- Mergenhagen KA, Starr KE, Wattengel BA, et al.; Determining the Utility of Methicillin-Resistant Staphylococcus aureus Nares Screening in Antimicrobial Stewardship. Clin Infect Dis. 2020 Aug 22;71(5):1142-1148.
