Key Point:

Combination antibiotic therapy can lower mortality in critically ill, but not in less severely ill, patients with pneumococcal bacteremia.

ROCHESTER, MINN—Critically ill patients with bacteremia caused by Streptococcus pneumoniae often die from the infection. Findings from a new study, however, suggest that treatment with combination antibiotics can double the 14-day survival rate among critically ill patients—but not less severely ill patients—infected with the pathogen.¹

Larry M. Baddour, MD, and colleagues conducted a prospective, multicenter, observational study examining the effect of combination antibiotic therapy versus monotherapy on 14-day mortality among 844 patients with bacteremia caused by S pneumoniae. The most commonly prescribed monotherapy regimens for these critically ill patients were β-lactam agents, azithromycin, ciprofloxacin, and clindamycin. The combination therapies most frequently prescribed were β-lactams paired with either macrolide agents, vancomycin, aminoglycoside agents, quinolones, chloramphenicol, or trimethoprim-sulfamethoxazole; vancomycin with another antibiotic; double β-lactam therapy; or clindamycin with quinolones. According to Dr. Baddour, a Professor of Medicine at the Mayo Clinic College of Medicine in Rochester, Minnesota, “Combination antibiotic therapy reduces mortality rates among critically ill patients with pneumococcal bacteremia. This syndrome is relatively common, and our findings should impact the care of a large number of patients.”

WHAT COMBINATION THERAPY CAN DO

The overall 14-day mortality rate was high, at 16.5%. Critically ill patients had an eightfold increased risk of death compared with less ill patients. The 14-day mortality was not significantly different for all patients receiving combination therapy versus monotherapy (10.4% vs 11.5%). Among critically ill patients, however, combination therapy was associated with lower 14-day mortality compared with monotherapy (23.4% vs 55.3%). The difference remained significant when analyzed according to in vitro activity and antibiotic resistance. Among the 112 patients admitted to the ICU, mortality was again significantly lower among those receiving combination therapy (8.2%) than in those receiving monotherapy (23.1%).

Did the type of antibiotic make a difference? Mortality rates were lowest among combination regimens that included β-lactams (26.8%), vancomycin (6.3%), and macrolides (14.3%), compared with monotherapy. The mortality was 26.8% for those receiving a β-lactam plus another antibiotic, compared with 58.4% for those receiving β-lactams as monotherapy. The promising survival rates seen with combination therapy could be a result of its ability to quickly kill pneumococci. Or, the combination regimen “may alter the inflammatory reaction that can impact the severity of sepsis,” suggested Dr. Baddour. Alternatively, combination antibiotics may treat copathogens that are also infecting the patient. Dr. Baddour called for more research into the mechanisms behind the reduced mortality observed with antibiotic combinations.

He reiterated that the survival benefits of combination antibiotic therapy were observed only in critically ill patients and cautioned that combination therapy “should not be administered to lesser ill patients [because clinicians should limit] unnecessary antibiotic use.” Furthermore, he added, “the risk of mortality among less ill patients is very low, and so combination antibiotic therapy will add nothing.”

—Tamara Gibb

Reference
1. Baddour LM, Yu VL, Klugman KP, et al. Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med. 2004;170:440-444.

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