Failure of Macrolide Antibiotic Treatment in Patients with Bacteremia Due to Erythromycin‐ResistantStreptococcus pneumoniae

Abstract

The rate of macrolide resistance among Streptococcus pneumoniae is increasing, but some investigators have questioned its clinical relevance. We conducted a matched case-control study of patients with bacteremic pneumococcal infection at 4 hospitals to determine whether development of breakthrough bacteremia during macrolide treatment was related to macrolide susceptibility of the pneumococcal isolate. Case patients (n=86) were patients who had pneumococcal bacteremia and an isolate that was either resistant or intermediately resistant to erythromycin. Controls (n=141) were patients matched for age, sex, location, and year that bacteremia developed who had an erythromycin-susceptible pneumococcus isolated. Excluding patients with meningitis, 18 (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture (P=.00000012). Moreover, 5 (24%) of 21 case patients with the low-level-resistant M phenotype and none of 40 controls were taking a macrolide (P=.00157). These data show that development of breakthrough bacteremia during macrolide or azalide therapy is more likely to occur among patients infected with an erythromycin-resistant pneumococcus, and they also indicate that in vitro macrolide resistance resulting from both the efflux and methylase mechanisms is clinically relevant.

Factors Associated With Antimicrobial Resistance and Mortality in Pneumococcal Bacteremia

“…Prior studies investigating the clinical relevance of antibiotic resistance and mortality in pneumococcal disease have been based on a much smaller number of patients. (11,12) In this large, retrospective mulitcenter cohort study of patients with pneumococcal bacteremia, we determine the relationship between prior antibiotic use and antibiotic resistance, and also determine which factors are associated with antibiotic resistance. We found that in addition to prior antibiotic use, having S. pneumoniae isolated from another site in addition to blood, residing the Southern US, and having an allergy to an antibiotic are independent risk factors for harboring a macrolide resistant organism.…”

“…There is literature suggesting that antibiotic resistance may contribute to treatment failure and poor clinical outcomes. (7,(9)(10)(11) Cases of failed therapy in association with resistance have been reported, but large-scale clinical studies of this phenomenon are lacking. The result is poor consensus regarding the clinical implications of antimicrobial resistance.…”

Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review

“…Beta-lactam and macrolide resistance in S pneumoniae now threatens routine management of CAP, 7,8 and beta-lactamase production in Haemophilus influenzae and Moraxella catarrhalis has compromised the use of beta-lactams in AECB. The fluoroquinolones offer potent, first-choice alternative therapies to traditional agents.…”

Novel pharmaceutical molecules against emerging resistant gram-positive cocci

“…24,25 These resistant isolates are often also resistant to macrolides, and in vitro resistance to macrolide does appear to correlate with clinical outcome. 26,27 In adult patients, S. pneumoniae also represents the most common cause of meningitis. Empiric therapy for meningitis with ceftriaxone and vancomycin pending antibiotic susceptibility testing is often employed.…”