Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis

Abstract

cIncreasing numbers of admissions for sepsis impose a heavy burden on health care systems worldwide, while novel therapies have proven both expensive and ineffective. We explored the long-term mortality and hospitalization costs after adjunctive therapy with intravenous clarithromycin in ventilator-associated pneumonia (VAP). Two hundred patients with sepsis and VAP were enrolled in a published randomized clinical trial; 100 were allocated to blind treatment with a placebo and another 100 to clarithromycin at 1 g daily for three consecutive days. Long-term mortality was recorded. The hospitalization cost was calculated by direct quantitation of imaging tests, medical interventions, laboratory tests, nonantibiotic drugs and antibiotics, intravenous fluids, and parenteral and enteral nutrition. Quantities were priced by the respective prices defined by the Greek government in 2002. The primary endpoint was 90-day mortality; cumulative hospitalization cost was the secondary endpoint. All-cause mortality rates on day 90 were 60% in the placebo arm and 43% in the clarithromycin arm (P ‫؍‬ 0.023); 141 patients were alive on day 28, and mortality rates between days 29 and 90 were 44.4% and 17.4%, respectively (P ‫؍‬ 0.001). The mean cumulative costs on day 25 in the placebo group and in the clarithromycin group were €14,701.10 and €13,100.50 per patient staying alive, respectively (P ‫؍‬ 0.048). Respective values on day 45 were €26,249.50 and €19,303.10 per patient staying alive (P ‫؍‬ 0.011); this was associated with the savings from drugs other than antimicrobials. It is concluded that intravenous clarithromycin for three consecutive days as an adjunctive treatment in VAP and sepsis offers long-term survival benefit along with a considerable reduction in the hospitalization cost. (This study has been registered at ClinicalTrials.gov under registration no. NCT00297674.)

Resistance Trends and Treatment Options in Gram-Negative Ventilator-Associated Pneumonia

“…Yet these agents can produce potentially beneficial immunomodulatory changes in pneumonia. A multicenter, double-blinded study of 200 ICU patients with sepsis and VAP found that adjunctive clarithromycin led to earlier VAP resolution and faster mechanical ventilation weaning [93, 94]. …”

Clarithromycin Plus Intravenous Immunoglobulin Therapy Can Reduce the Relapse Rate of Kawasaki Disease: A Phase 2, Open‐Label, Randomized Control Study

“…The use of macrolides dramatically improved the prognosis of patients with diffuse panbronchiolitis. Furthermore, clarithromycin lengthened the survival in patients with ventilator‐associated pneumonia and sepsis and shortened the time to the resolution of infection among patients with pyelonephritis, intra‐abdominal infections, and Gram‐negative bacteremia . The mechanisms by which macrolides improve these diseases remain to be clarified.…”

Health economic evaluations of sepsis interventions in critically ill adult patients: a systematic review

“…Five evaluations examined antibiotic interventions [22][23][24][25][26], two examined fluid therapies [27,28], eight examined EGDT or other (primarily emergency department [ED]-based) resuscitation protocols [35][36][37][38][39][40][41][42]71], three examined procalcitonin algorithms [29][30][31], two examined immunoglobulin therapies [32][33][34], four examined methods of pathogen identification [43][44][45][46], one examined point of care lactate testing [47], and one examined immediate ICU admission [48]. The remaining 20 evaluations examined interventions no longer used in clinical practice-13 examined drotrecogin alfa (activated) (51-64), and seven examined monoclonal antibodies [64][65][66][67][68][69][70].…”

“…The reporting quality varied widely, with scores ranging from 13% (3/23) [65] to 95% (21/22) [42,50]. Twelve (26%) of the studies were found to be of excellent [22][23][24][25][26] Fluid therapies 2 (4%) [27,28] Procalcitonin algorithms 3 (7%) [29][30][31] Immmunoglobulin therapies 2 (4%) [32][33][34] EGDT or other sepsis protocol 8 (17%) [35][36][37][38][39][40][41][42][43] Pathogen identification 4 (9%) [44][45][46][47] Other 2 (4%) [48,49] Interventions no longer in clinical practice reporting quality, 18 (39%) of very good quality, 11 (24%) of good quality, and 5 (11%) of poor quality. The quality of evaluations published in the past 15 years was higher (average 75%) than evaluations published prior to 2005 (average 58%), with the quality of evaluations varying by intervention-88% of EGDT and resuscitation protocol evaluations were of very good or excellent quality compared to 60% of evaluations of antibiotic therapies and 25% of evaluations of pathogen identification (Additional file 4).…”