Usefulness of Betalactam Therapy for Community-Acquired Pneumonia in the Era of Drug-ResistantStreptococcus pneumoniae:A Randomized Study of Amoxicillin-Clavulanate and Ceftriaxone

Abstract

Empirical antibiotic therapy of community-acquired pneumonia (CAP) has been complicated by the worldwide emergence of penicillin resistance among Streptococcus pneumoniae. The impact of this resistance on the outcome of patients hospitalized for CAP, empirically treated with betalactams, has not been evaluated in a randomized study. We conducted a prospective, randomized trial to assess the efficacy of amoxicillin-clavulanate (2 g/200 mg/8 hr) and ceftriaxone (1 g/24 hr) in a cohort of patients hospitalized for moderate-to-severe CAP. Three-hundred seventy-eight patients were randomized to receive amoxicillin-clavulanate (184 patients) or ceftriaxone (194 patients). Efficacy was assessed on Day 2, after completion of therapy and at long term follow-up. There were no significant differences in outcomes between treatment groups, both in intention-to-treat and per-protocol analysis. Overall mortality was 10.3% for amoxicillin-clavulanate and 8.8% for ceftriaxone (NS). There were 116 evaluable patients with proven pneumococcal pneumonia. Rates of highlevel penicillin resistance (MIC of penicillin $2 l g/mL) were similar in the two groups (8.2 and 10.2%). Clinical efficacy at the end of therapy was 90.6% for amoxicillin-clavulanate and 88.9% for ceftriaxone (95% C.I. of the difference: 2 9.3 to 1 12.7%). No differences in outcomes were attributable to differences in penicillin susceptibility of pneumococcal strains. Sequential i.v./oral amoxicillin-clavulanate and parenteral ceftriaxone were equally safe and effective for the empirical treatment of acute bacterial pneumonia, including penicillin and cephalosporin-resistant pneumococcal pneumonia. The use of appropriate betalactams in patients with penumococcal pneumonia and in the overall CAP population, is reliable at the current level of resistance. 85

Community-acquired pneumonia in Europe: causative pathogens and resistance patterns

“…There are no studies to date for CAP in Europe that indicate the frequency of isolates with an MIC of ¢4 mg?mL -1 , which is what the prescriber would want to know most [82]. A recent prospective treatment study from Barcelona found that only 10 of 116 (9%) adults admitted to hospital with pneumococcal pneumonia had pneumococci with an MIC of ¢2 [83]. Outcome was the same in the co-amoxiclav treated group as in the ceftriaxone treated group.…”

Investigation of The Protective Effects of Beta-D-Glucan Against Invasive Encapsulated Streptococcus pneumoniae Sepsis in Splenectomized Rats

“…Ancak oluşan infl amatuar yanıt düzeyinin düşük olması ve BDG'ın antioksidan özellikleri, doku hasarının bir göstergesi olan DNA oksidasyonunun diğer tedavi gruplarına benzer çıkmasına neden olmuştur. Mikrobiyolojik analizlerde, seftriakson ve BDG+seftriakson grubunun akciğerlerinde bakteri yükünün az olması, seftriaksonun S.pneumoniae üzerine direkt antimikrobiyal özelliğinden kaynaklanmaktadır 25,26 . BDG grubunda bakteriyemi varlığının sepsis grubuna göre düşük olması; hem IgM'ye bağlı mekanizmalara, hem de daha önceki çalışmalarda 27 bulunan BDG'ın lektine bağımlı ve alternatif kompleman yollarını aktive edici mekanizmalarından kaynaklanmış olabilir.…”

Community‐Acquired Pneumonia

“…One RCT compared penicillin (intravenous [iv] co-amoxiclav [amoxicillin-clavulanic acid] followed by oral co-amoxiclav) versus cephalosporins (iv ceftriaxone followed by intramuscular [im] ceftriaxone). [18] -…”

“…Clinical cure , long-term followup (not specified) 136/184 (73.9%) with intravenous (iv) co-amoxiclav (amoxi-378 people [18] RCT cillin-clavulanic acid) followed by oral co-amoxiclav) 144/194 (74.2%) with iv ceftriaxone followed by intramuscular (im) ceftriaxone …”

“…Directness point deducted as low mortality in studies (3.2%) as compared with normally seen in this group (10%), which may affect generalisability Low 0 -1 0 -1 4 Atypical coverage regimens versus non-atypical coverage regimens Mortality 24 (5244) [17] Quality point deducted for weak methods (allocation concealment, blinding). Directness point deducted as low mortality in studies (3.2%) as compared with normally seen in this group (10%), which may affect generalisability Low 0 -1 0 -1 4 Atypical coverage regimens versus non-atypical coverage regimens Clinical cure 25 (5053) [17] Directness points deducted for inclusion of co-intervention (erythromycin) and unclear follow-up Low 0 -2 0 0 4 Penicillin versus cephalosporins Clinical cure 1 (378) [18] Quality point deducted for no intention-to-treat analysis. Directness point deducted for inclusion of co-intervention Clinical cure 1 (480) [19] Quality point deducted for no intention-to-treat analysis Moderate 0 0 0 -1 4 Daptomycin versus ceftriaxone Clinical cure 2 (834) [20] Quality point deducted for group randomisation.…”