Empiric antibiotics for community-acquired pneumonia in adult patients: a systematic review and a network meta-analysis.

OBJECTIVE: The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) . METHOD: Inclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish. EXCLUSION CRITERIA: (1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format. DATA SOURCES: Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane's tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation. STATISTICAL ANALYSES: frequentist method performed with the 'netmeta' library, R package. RESULTS: 27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. For cure, two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). For mortality, three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate. CONCLUSION: For cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692).

What have we learned from network meta-analyses applied to critical care?

It is widely accepted in modern medicine that medical decisions must be supported by scientific evidence. Identifying the best intervention when several options are available constitute a great challenge for every clinician. Traditional meta-analysis (TMA) allows summarizing evidence from studies that compare the same two interventions for one event (head to head studies or direct comparisons). Network meta-analysis (NMA) is a relatively new procedure that allows to compare multiple interventions for one event, even when non-head to head studies have been conducted (indirect evidence). Other advantages of NMA include increasing the accuracy of the results and ranking all the interventions according to their effectiveness. These features are of paramount importance as: 1) they summarize information from events (e.g. diseases or outcomes) that has more than two possible interventions (e.g. treatments or procedures); 2) they strengthen the level of guideline recommendations; and 3) they identify new hypotheses based on indirect comparison. As this is a narrative review, all manuscripts have been selected from PubMed according to our best knowledge with the aim to illustrate different features, options or applications of NMA in critical care. First, we provide a description of the usefulness, interpretation, assumptions and main plots related to NMAs. Second, we analyzed some examples of NMAs related to critical care medicine. Third, we include a pragmatic approach about how results from NMAs can improve the clinical practice as well an R script with a database to conduct an NMAs and reproduce figures and tables that have been shown here. As a conclusion, NMA is an established, robust, objective and reproducible statistic technique that has been applied to several critical care areas. Clinical practice guidelines have started to include NMA evidence to support their recommendations. In future years, it seems highly probable that this technique will increase it applicability in almost all areas of critical care medicine.