Meta‐analysis: randomized controlled trials of clindamycin/aminoglycoside vs. β‐lactam monotherapy for the treatment of intra‐abdominal infections

Abstract

SUMMARY AimTo compare the effectiveness and safety of clindamycin ⁄ aminoglycoside with broad-spectrum b-lactam monotherapy in patients with intraabdominal infections by performing a meta-analysis of randomized controlled trials (RCTs). MethodsThe relevant 28 RCTS were retrieved from PubMed searches and reviewed by two reviewers independently.Results b-lactam monotherapy was more effective regarding cure of the infection than clindamycin ⁄ aminoglycoside (3177 clinically evaluable patients, fixed effects model, OR = 0.67, 95% CI: 0.55-0.81). The same result was found in several subset analyses. There was no difference in all-cause mortality and attributable-to-infection mortality [2382 intention-to-treat (ITT) patients, fixed effects model, OR = 1.25, 95% CI: 0.74-2.11 and 1976 ITT patients, OR = 1.19, 95% CI: 0.59-2.41, respectively]. There was no difference regarding overall adverse events and ototoxicity (1460 ITT patients, OR = 1.05, 95% CI: 0.80-1.37, and 1404 ITT patients, OR = 3.22, 95% CI: 0.72-14.45, respectively). However, treatment with clindamycin ⁄ aminoglycoside was more likely to be associated with nephrotoxicity compared to b-lactam (3065 ITT patients, OR = 3.7, 95% CI: 2.09-6.57). Clindamycin ⁄ aminoglycoside was less likely to be associated with antibiotic-associated diarrhoea compared to b-lactam (3050 ITT patients, OR = 0.68, 95% CI: 0.46-1.00). ConclusionThe results of our meta-analysis suggest that b-lactams are more effective in the treatment of intra-abdominal infections compared with clindamycin ⁄ aminoglycoside.

Restrictive antibiotic stewardship associated with reduced hospital mortality in gram-negative infection

“…A meta-analysis of clinical trials involving gentamicin found similar outcomes to comparator antibiotics but only a small proportion of patients had sepsis (16). Another meta-analysis of heterogenous studies in secondary peritonitis found lower rates of clinical cure in patients treated with clindamycin and gentamicin although mortality was not affected (17). Clinical outcome data following severe infection managed using restrictive guidelines are extremely limited.…”

“…Specific concerns included the potential for increased incidence of acute kidney injury and ototoxicity as well as the relative paucity of data supporting the use of gentamicin monotherapy in severe infection (16,17). In view of the potential for unintended harm, it was recommended that gentamicin was restricted to the empiric phase of therapy with a maximum duration of 4 days.…”

Risk of AKI with Gentamicin as Surgical Prophylaxis

“…21 Several recent meta-analyses have shown that the risk of AKI as a result of aminoglycosides is high when used for the empirical treatment of severe Gram-positive or Gram-negative bacterial infections. [22][23][24][25] Therefore, the KDIGO AKI guideline recommends that aminoglycosides should not be used for the treatment of infection unless no suitable, less nephrotoxic therapeutic alternatives are available. 16 However, concerns regarding antimicrobial resistance as well as increasing rates of CDI have led to continued widespread gentamicin use.…”

La conexión neumocóccica

“…Tema controversial, si bien consensos estadounidenses y canadienses recomiendan esquemas que no incluyen aminoglucósidos-aminociclitoles por menor eficacia y toxicidad 58,59 , al revisar meta-análisis que apoyan esta postura se observa mortalidades equivalentes al comparar esquemas con aminoglucósidos más agente antianaeróbico versus comparadores 60,61 , lo mismo una revisión sistemática que además sugiere en sus conclusiones que deben considerarse guías locales y costos junto con nuevos estudios que logren estratificar a los diferentes grupos de pacientes 62 . De lo anterior se deriva que, en pacientes adultos jóvenes, sin injuria renal, ni shock séptico, la asociación de gentamicina en monodosis diaria más metronidazol es una alternativa válida, particularmente considerando que la resolución del cuadro es quirúrgica y que la terapia antimicrobiana es sólo coadyuvante…”

“…A pesar de lo señalado por líderes de opinión estadounidenses que favorecen el uso de ceftriaxona 61 , nuestra postura enfatiza uso de isoxazolil penicilinas. Un reciente estudio demuestra equivalencia entre monoterapia con flucloxacilina versus flucloxacilina más benzilpenicilina 64 .…”