Carbapenems for the Empiric Treatment of Nosocomial Pneumonia: A Systematic Review and Meta-analysis
CCCF ePoster library. Howatt M. Nov 8, 2018; 233385
Mackenzie Howatt
Mackenzie Howatt
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Abstract
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Background: Hospital Acquired Pneumonia (HAP), including Ventilator Associated Pneumonia (VAP) is a common complication of hospitalization that increases morbidity, mortality, and healthcare costs. Inadequate or inappropriate therapy is associated with higher mortality rates. Carbapenems, a class of antibiotics with broad activity against many gram positive and negative pathogens causal for HAP, are a potential option for inclusion into empiric therapy regimens. However, concerns over the broad spectrum of carbapenem activity, the development of resistance and the perception that carbapenems need to be reserved as antibiotics of last resort have limited their utilization. To understand their role as empiric therapy in the treatment of HAP, the efficacy and safety of carbapenems in this context must be better understood and hence we undertook a systemic review and meta-analysis of evidence to date. 



Objectives: To determine the impact of carbapenems when included in empiric regimens for HAP (including VAP) on clinical outcomes including mortality, clinical resolution, and development of resistance.



Methods: We conducted a systematic review and meta-analysis by searching EMBASE, MEDLINE, and EBM for potential studies up to April 2018. Titles and abstracts were reviewed in duplicate. Inclusion criteria were randomized controlled studies that included an empiric regimen with a carbapenem in one treatment arm for the treatment of HAP including VAP. The primary outcome was all cause mortality at the longest time point specified by the authors. Secondary outcomes included clinical resolution of pneumonia, and the development of resistance. We determined Risk Ratios (RR) for each outcome using a random effects model. Heterogeneity was determined using Chi-squared test and interclass correlation (I2).



Results: Of 14,369 unique references, 20 trials enrolling a total of 4851 patients met the inclusion criteria and were included. For the primary outcome of mortality, carbapenem use had a RR of 0.81 (95% CI 0.71 – 0.93, p = 0.003) (Figure 1). When stratified by proportion of VAP (<33%, 33-66%, >66%) RR were 0.92 (0.69 – 1.23, p = 0.59), 0.78 (0.57 – 1.07, p = 0.13), and 0.80 (0.65 – 0.99, p = 0.04), respectively. The overall clinical response had a RR of 1.03 (0.98 – 1.09, p = 0.24) (Figure 2), and there was a trend toward the development of increased resistance use with carbapenems with a RR of 1.44 (0.98 – 2.11, p =0.06) (Figure 3). There was no significant statistical heterogeneity and visual inspection of the funnel plot did not reveal evidence of publication bias.



Conclusions: Carbapenem use was associated with decreased mortality but not with increased clinical resolution of HAP when compared to alternative regimens. There was also a trend towards increased development of resistance with carbapenem use although these data were not available for many included studies. Although these data suggest that the use of carbapenems as empiric therapy may reduce mortality, their use must be balanced with local susceptibility patterns, and potential for development of new resistance. Limitations of this meta-analysis include that many studies only followed patients for a short time, had significant risk of bias, and had inconsistent reporting of developing resistance. More research is required to determine if there is a subset of patients suspected of HAP for which a carbapenem is the most appropriate empiric therapy.


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