These are described in detail in the Methods section on page 519.
ReviewDoes combination antimicrobial therapy reduce mortality in Gram-negative bacteraemia? A meta-analysis
Section snippets
Search strategy and selection criteria
We searched the following databases: Medline (Jan 1 1966–2003), Current Contents (Jan 1 1993–Aug 1 2003), Pubmed (Jan 1 1966–Aug 1, 2003), CancerLit, and the Cochrane Network. The following MeSH keywords were used alone and in combination: “Gram-negative bacteraemia”, “combination antibiotic”, “antibiotic”, “antimicrobial”, “mortality”, “Pseudomonas aeruginosa”, “Serratia”, “Klebsiella”, “Escherichia coli”, “bloodstream infection”, and “neutropenic fever”. The term Gram-negative bacteraemia was
Results
Of the 471 studies identified by the initial search strategy, 17 met the inclusion criteria, encompassing 3077 patients.19, 20, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 The remainder were excluded because they did not adequately compare combination and single antimicrobial therapy (326), were not studies of bacteraemia (76), did not use mortality as an outcome measure (50), did not provide sufficient data to calculate an odds ratio for mortality (1),48 or had no fatal outcomes
Adverse events of monotherapy and combination therapy
Only one study44 reported the adverse effects of combination or monotherapy among the 17 included studies. In a randomised trial, de Pauw et al44 found that, overall, adverse events were 2·9 times more frequent in patients treated with the combination of piperacillin with tobramycin than in patients treated only with ceftazidime. The adverse effects consisted of renal toxicity, skin rash, and ototoxicity.
Discussion
Gram-negative bacilli cause serious, life-threatening infections, especially in neutropenic or critically ill patients. Several studies have convincingly shown that appropriate antimicrobial therapy, defined as the use of at least one antibiotic active in vitro against the causative organism, leads to lower mortality rates in Gram-negative bacteraemia. A landmark study by McCabe and Jackson50 in the early 1960s reported a reduction in mortality associated with Gram-negative bacteraemia in 173
Search strategy and selection criteria
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2020, International Journal of Antimicrobial AgentsCitation Excerpt :Despite the theoretical advantages of combination therapy, several meta-analyses have reported no improvement in mortality or clinical cure rates. These analyses included studies from various clinical settings, including sepsis, Pseudomonas aeruginosa bacteraemia and febrile neutropaenia [7–10]. Indeed, published studies indicate that such combinations may be harmful because of a possible increased risk of nephrotoxicity with aminoglycoside-based combination regimens [5,7–11].