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).

Hospital Mortality and Effect of Adjusting PaO2/FiO2 According to Altitude Above the Sea Level in Acclimatized Patients Undergoing Invasive Mechanical Ventilation. A Multicenter Study.

OBJECTIVE: (i) Analyze the effect of altitude above the sea level on the mortality rate in patients undergoing invasive mechanical ventilation. (ii) Validate the traditional equation for adjusting PaO2/FiO2 according to the altitude. DESIGN: A prospective, observational, multicenter and international study conducted during August 2016. PATIENTS: Inclusion criteria: (i) age between 18 and 90 years old, (ii) admitted to intensive care unit (ICU) situated at the same altitude above the sea level (AASL) in which the patients has stayed, at least, during the previous 40 days and (iii) received invasive MV for at least 12h. MATERIAL AND METHODS: All variables were registered the day of intubation (day 0). Patients were followed until death, ICU discharge or day 28. PaO2/FiO2 ratio was adjusted by the AASL according to: PaO2/FiO2*(barometric pressure/760). Categorical variables were compared with χ2 and Cochran-Mantel-Haenszel test. Continuous variables with Mann-Whitney. Correlation between continuous variables was analyzed graphically and analytically. Logistic regression model was constructed to identify factors associated to mortality. Kapplan-Meier method was used to estimate the probability of survival according to the altitude. A 2-side p value <0.05 was consider significant. RESULTS: 249 patients (<1500m n=55; 1500 to <2500m n=20; 2500 to <3500m n=155 and ≥3500m n=19) were included. Adjusted and non-adjusted PaO2/FiO2 were correlated with several respiratory and non respiratory variables. None discordances between non adjusted and adjusted PaO2/FiO2 were identified. However, several correlations were appreciated only in patients situated <1500m or in >1500m. Seventy-nine patients died during the ICU stayed (32%). The mortality curve was not affected by the altitude above the sea level. Variables independently associated to mortality are: PEEP, age, systolic arterial blood pressure, and platelet count. AUROC: 0.72. CONCLUSION: In acclimatized patients undergoing invasive mechanical ventilation, the traditional equation for adjusting PaO2/FiO2 according the elevation above the sea level seems to be inaccurate and the altitude above the sea level does not affect the mortality risk.

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.

Should we consider IgG hypogammaglobulinemia a risk factor for severe complications of Ludwig angina?: A case report and review of the literature.

RATIONALE: Cervical necrotizing fasciitis (CNF) and descending necrotizing mediastinitis (DNM) are rare forms of complication of Ludwig angina. These potentially lethal infections are difficult to recognize in early stages and are often associated with predisposing factors like diabetes and immunocompromised states. Moreover, IgG hypogammaglobulinemia (hypo-IgG) is considered to be a risk factor of mortality in patients with septic shock; however, it is not routinely quantified in patients with extremely serious infections, particularly in cases with no history or evidence of immunocompromising disorders. PATIENT CONCERNS: We present a case of a 58-year-old woman who survived Ludwig angina, complicated by CNF and DNM. Despite a rapid diagnosis, aggressive surgical debridement and broad-spectrum antibiotics, the infection and necrosis advanced, requiring multiple surgical interventions and long intensive care unit (ICU) support. CONCLUSION: We hypothesize that detecting a low level of endogenous IgG and treating with adjuvant passive immunotherapy was key in determining a favorable outcome.