Severe community-acquired pneumonia: current concepts and controversies

Intensive Care Medicine | Published: 12 January 2026

Abstract

Community-acquired pneumonia, particularly in its severe forms (sCAP), remains a major public health problem due to its frequency, immediate and delayed complications, and the cost of treatment. Although rare, resistant pathogens could make it increasingly difficult to choose an empirical antibiotic treatment. Rapid molecular microbiological diagnostic techniques could help guide this choice, but their role needs to be better evaluated and their cost may be an obstacle to their widespread use. The duration of treatment tends to be decreasing, but could be guided by clinical progression and possibly biomarkers. As a disorder of dysregulated systemic inflammation, sCAP is potentially eligible for immunomodulatory treatment. Three recent high-powered randomized trials on corticosteroids have yielded conflicting results. There is a need to better define which patients are likely to benefit, perhaps those with a marked inflammatory syndrome, and in any case not those with influenza. Some macrolides also have a potential immunomodulatory effect. Other treatments are currently being investigated. Supportive care, particularly respiratory support, remains essential. It is not specific to sCAP and must be tailored to the severity of the patient's condition.

Critical Care Bulletin: October 2025

 

Antibiotic therapy in necrotizing soft tissue infections: a narrative review of the greater Paris SURFAST consortium

Critical Care volume 29, Article number: 431 (2025)  Published: 10 October 2025

Abstract

Necrotizing soft tissue infections (NSTIs) are uncommon, yet rapidly progressive and potentially fatal conditions. However, evidence-based guidance on antibiotic therapy remains limited. Current recommendations emphasize the need for broad-spectrum empirical coverage, including gram-positive, gram-negative, anaerobes, and Streptococcus pyogenes when clinically indicated. We aimed at developing a practical, evidence-based framework for empirical antibiotic therapy in NSTIs. This narrative review is informed by a comprehensive literature search of PubMed, without date restrictions. We propose a structured decision-making algorithm for empirical antibiotic selection in NSTIs, integrating key clinical parameters: infection site, healthcare-associated versus community-acquired origin, risk factors for extended-spectrum β-lactamase-producing Enterobacterales and methicillin-resistant Staphylococcus aureus, and signs of sepsis or septic shock. Alternative regimens are provided for patients with severe β-lactam allergies. Special considerations for immunocompromised and other vulnerable host populations are also addressed. This review offers clinicians a pragmatic, stepwise approach to antibiotic therapy in NSTIs, while identifying critical knowledge gaps and priorities for future research.

 

Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot safety and feasibility randomised controlled trial

 

Intensive Care Medicine: Published 13 May 2024

Purpose

Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness.

Methods

Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation.

Results

We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019).

Conclusion

These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.

 

Efficacy and safety of antibiotics targeting Gram-negative bacteria in nosocomial pneumonia: a systematic review and Bayesian network meta-analysis

 by David Luque Paz, Dara Chean, Pierre Tattevin, Damien Luque Paz, Betsega Assefa Bayeh, Achille Kouatchet, Delphine Douillet and Jérémie Riou

 Annals of Intensive Care volume 14, Article number: 66, Published: 25 April 2024

Background

Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP.

Methods

We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events.

Results

Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17–0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19–3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00–2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03–2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02–2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin.

Conclusions

This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria.

Registration PROSPERO CRD42021226603

 

Acute-on-chronic liver failure alters linezolid pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study

 

by Tjokosela Tikiso, Valentin Fuhrmann, Christina König, Dominik Jarczak, Stefanie Iwersen-Bergmann, Stefan Kluge, Sebastian G. Wicha and Jörn Grensemann 

 

Annals of Intensive Care volume 13, Article number: 83 (2023)

 

Background

In acute-on-chronic liver failure (ACLF), adequate antibiotic dosing is challenging due to changes of drug distribution and elimination. We studied the pharmacokinetics of linezolid in critically ill patients with ACLF during continuous renal replacement therapy compared to patients without concomitant liver failure (NLF).

Methods

In this prospective cohort study, patients received linezolid 600 mg bid. Linezolid serum samples were analyzed by high-performance liquid chromatography. Population pharmacokinetic modelling was performed followed by Monte-Carlo simulations of 150 mg bid, 300 mg bid, 450 mg bid, 600 mg bid, and 900 mg bid to assess trough concentration target attainment of 2–7 mg/L.

Results

Eighteen patients were included in this study with nine suffering from ACLF. Linezolid body clearance was lower in the ACLF group with mean (standard deviation) 1.54 (0.52) L/h versus 6.26 (2.43) L/h for NLF, P < 0.001. A trough concentration of 2–7 mg/L was reached with the standard dose of 600 mg bid in the NLF group in 47%, with 42% being underexposed and 11% overexposed versus 20% in the ACLF group with 77% overexposed and 3% underexposed. The highest probability of target exposure was attained with 600 mg bid in the NLF group and 150 mg bid in the ACLF group with 53%.

Conclusion

Linezolid body clearance in ACLF was markedly lower than in NLF. Given the overall high variability, therapeutic drug monitoring (TDM) with dose adjustments seems required to optimize target attainment. Until TDM results are available, a dose reduction may be considered in ACLF patients to prevent overexposure.

 

Time to treatment and mortality for clinical sepsis subtypes

 

by Anne Yang, Jason N. Kennedy, Katherine M. Reitz, Gary Phillips, Kathleen M. Terry, Mitchell M. Levy, Derek C. Angus and Christopher W. Seymour 

 

Critical Care volume 27, Article number: 236 Published: 15 June 2023

 

Background

Sepsis is common, deadly, and heterogenous. Prior analyses of patients with sepsis and septic shock in New York State showed a risk-adjusted association between more rapid antibiotic administration and bundled care completion, but not an intravenous fluid bolus, with reduced in-hospital mortality. However, it is unknown if clinically identifiable sepsis subtypes modify these associations.

Methods

Secondary analysis of patients with sepsis and septic shock enrolled in the New York State Department of Health cohort from January 1, 2015 to December 31, 2016. Patients were classified as clinical sepsis subtypes (α, β, γ, δ-types) using the Sepsis ENdotyping in Emergency CAre (SENECA) approach. Exposure variables included time to 3-h sepsis bundle completion, antibiotic administration, and intravenous fluid bolus completion. Then logistic regression models evaluated the interaction between exposures, clinical sepsis subtypes, and in-hospital mortality.

Results

55,169 hospitalizations from 155 hospitals were included (34% α, 30% β, 19% γ, 17% δ). The α-subtype had the lowest (N = 1,905, 10%) and δ-subtype had the highest (N = 3,776, 41%) in-hospital mortality. Each hour to completion of the 3-h bundle (aOR, 1.04 [95%CI, 1.02–1.05]) and antibiotic initiation (aOR, 1.03 [95%CI, 1.02–1.04]) was associated with increased risk-adjusted in-hospital mortality. The association differed across subtypes (p-interactions < 0.05). For example, the outcome association for the time to completion of the 3-h bundle was greater in the δ-subtype (aOR, 1.07 [95%CI, 1.05–1.10]) compared to α-subtype (aOR, 1.02 [95%CI, 0.99–1.04]). Time to intravenous fluid bolus completion was not associated with risk-adjusted in-hospital mortality (aOR, 0.99 [95%CI, 0.97–1.01]) and did not differ among subtypes (p-interaction = 0.41).

Conclusion

Timely completion of a 3-h sepsis bundle and antibiotic initiation was associated with reduced risk-adjusted in-hospital mortality, an association modified by clinically identifiable sepsis subtype.

Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A Murine Trial*

Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A Murine Trial*

by Lewis, Anthony J.; Griepentrog, John E.; Zhang, Xianghong; Angus, Derek C.; Seymour, Christopher W.; Rosengart, Matthew R.

Critical Care Medicine: May 2018 - Volume 46 - Issue 5 - p e426–e434

Objectives: Sepsis, the acute organ dysfunction caused by a dysregulated host response to infection, poses a serious public health burden. Current management includes early detection, initiation of antibiotics and fluids, and source control as necessary. Although observational data suggest that delays of even a few hours in the initiation of antibiotics or IV fluids is associated with survival, these findings are controversial. There are no randomized data in humans, and prior animal studies studied time from experimental manipulation, not from the onset of clinical features of sepsis. Using a recently developed murine cecal ligation and puncture model that precisely monitors physiologic deterioration, we hypothesize that incremental hourly delays in the first dose of antibiotics, in the first bolus of fluid resuscitation, or a combination of the two at a clinically relevant point of physiologic deterioration during polymicrobial sepsis will shorten survival. Design: Randomized laboratory animal experimental trial. Setting: University basic science laboratory. Subjects: Male C57BL/6J, female C57BL/6J, aged (40–50 wk old) male C57BL/6J, and BALB/C mice. Interventions: Mice (n = 200) underwent biotelemetry-enhanced cecal ligation and puncture and were randomized after meeting validated criteria for acute physiologic deterioration. Treatment groups consisted of a single dose of imipenem/cilastatin, a single bolus of 30 mL/kg fluid resuscitation, or a combination of the two. Mice were allocated to receive treatment at the time of meeting deterioration criteria, after a 2-hour delay or after a 4-hour delay. Measurements and Main Results: Hourly delays in the initiation of antibiotic therapy led to progressively shortened survival in our model (p < 0.001). The addition of fluid resuscitation was unable to rescue animals, which received treatment 4 hours after meeting enrollment criteria. Systemic inflammation was increased, and host physiology was increasingly deranged with hourly delays to antibiotics. Conclusions: We conclude that antibiotic therapy is highly time sensitive, and efforts should be made to deliver this critical therapy as early as possible in sepsis, perhaps extending into the first point of medical contact outside the hospital.

Systematic Review and Meta-Analysis of Procalcitonin-Guidance Versus Usual Care for Antimicrobial Management in Critically Ill Patients: Focus on Subgroups Based on Antibiotic Initiation, Cessation, or Mixed Strategies*

Systematic Review and Meta-Analysis of Procalcitonin-Guidance Versus Usual Care for Antimicrobial Management in Critically Ill Patients: Focus on Subgroups Based on Antibiotic Initiation, Cessation, or Mixed Strategies*

by Lam, Simon W.; Bauer, Seth R.; Fowler, Robert; Duggal, Abhijit  

Critical Care Medicine: May 2018 - Volume 46 - Issue 5 - p 684–690

Objective: Numerous studies have evaluated the use of procalcitonin guidance during different phases of antibiotics management (initiation, cessation, or a combination of both) in patients admitted to ICUs. Several meta-analyses have attempted to generate an overall effect of procalcitonin-guidance on patient outcomes. However, combining studies from different phases of antibiotics management may not be appropriate due to the risk of clinical heterogeneity. The purpose of this systematic review and meta-analysis was to evaluate the effect of procalcitonin-guided strategies in different phases of antibiotics use. Data Sources: We searched MEDLINE and EMBASE from inception until November 1, 2017. Study Selection: We included randomized controlled trials that evaluated procalcitonin guidance compared with usual care for management of antibiotics in critically ill adult patients. Data Extraction: We extracted study details, patient characteristics, procalcitonin algorithm, and outcomes. Data Synthesis: We included 15 studies, from 1,624 abstracts identified based on our search strategy (three initiation, nine cessation, and three mixed). The pooled risk ratio for short-term mortality for the initiation, cessation, and mixed procalcitonin strategies were 1.00 (95% CI, 0.86–1.15,;p = 0.91), 0.87 (95% CI, 0.77–0.98; p = 0.02), and 1.01 (95% CI, 0.80–1.29; p = 0.93), respectively. Procalcitonin for cessation and mixed strategies was associated with decrease antibiotics duration (–1.26 d [p < 0.001] and –3.10 d [p =0.04], respectively). No differences were observed in other outcome measures. Conclusion: When evaluating all studies of procalcitonin-guided antibiotics management in critically ill patients, no difference in short-term mortality was observed. However, when only examining procalcitonin-guided cessation of antibiotics, lower mortality was detected. Future studies should focus specifically on procalcitonin for the cessation of antibiotics in critically ill patients.

Antimicrobial resistance and antibiotic stewardship programs in the ICU: insistence and persistence in the fight against resistance. A position statement from ESICM/ESCMID/WAAAR round table on multi-drug resistance.

Antimicrobial resistance and antibiotic stewardship programs in the ICU: insistence and persistence in the fight against resistance. A position statement from ESICM/ESCMID/WAAAR round table on multi-drug resistance.

Author(s) De Waele, Jan J; Akova, Murat; Antonelli, Massimo; Canton, Rafael; Carlet, Jean et al.

Source Intensive care medicine; Feb 2018; vol. 44 (no. 2); p. 189-196

Publication Date Feb 2018

DOI 10.1007/s00134-017-5036-1

ISSN 1432-1238

Database Medline

Antimicrobial resistance (AMR) is a clear and present danger to patients in any intensive care unit (ICU) around the world. Whereas AMR may affect any patient in the hospital, patients in the ICU are particularly at risk of acquiring AMR infections due to the intensity of the treatment, use of invasive devices, increased risk of transmission and exposure to antibiotics. AMR is present in every ICU, although prevalence is geographically different and AMR pathogens encountered are variable. Intensive care and infectious disease specialists from the European Society of Intensive Care Medicine, European Society of Microbiology and Infectious Diseases and World Alliance Against Antimicrobial Resistance, united in the ANTARCTICA (Antimicrobial Resistance in Critical Care) coalition, call for increased awareness and action among health care professionals to reduce AMR development in critically ill patients, to improve treatment of AMR infections and to coordinate scientific research in this high-risk patient population. Close collaboration with other specialties, and combining these and other interventions in antibiotic stewardship programmes should be a priority in every ICU. Considerate antibiotic use and adopting strict infection control practices to halt AMR remains a responsibility shared by all healthcare workers, from physicians to maintenance personnel, from nurses to physiotherapists, from consultants to medical students. Together, we can reduce AMR in our ICUs and continue to treat our patients effectively.

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States
Thomas, Z et al.
Critical Care Medicine: December 2015 - Volume 43 - Issue 12 - p 2527–2534


Objective: The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the prolonged empiric antibiotic therapy rate and certain ICU characteristics. Design: Multicenter, prospective, observational, 72-hour snapshot study. Setting: Sixty-seven ICUs from 32 hospitals in the United States. Patients: Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study. Intervention: None.
Measurements and Main Results: Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate.
Conclusions: Half of all empiric antibiotics ordered in critically ill patients are continued for at least 72 hours in absence of adjudicated infection. Additional studies are needed to confirm these findings and determine the risks and benefits of prolonged empiric therapy in the critically ill.

Time to Appropriate Antibiotic Therapy Is an Independent Determinant of Postinfection ICU and Hospital Lengths of Stay in Patients with Sepsis

Critical Care Medicine: October 2015 - Volume 43 - Issue 10 - p 2133–2140

Zhang, D

Objective: To assess the timing of appropriate antibiotic therapy as a determinant of postinfection hospital and ICU lengths of stay in patients with sepsis. Design: Single-center retrospective cohort study (January 2008–December 2012). Setting: One thousand two hundred fifty–bed academic hospital. Patients: One thousand fifty-eight consecutive blood culture positive patients. Interventions: We retrospectively identified adult patients with severe sepsis or septic shock. Timing of appropriate antibiotic therapy was determined from blood culture collection time to the administration of the first dose of antibiotic therapy with documented in vitro susceptibility against the identified pathogen. We constructed generalized linear models to examine the determinants of attributable lengths of stay. Measurements and Main Results: The median (interquartile range) time from blood culture collection to the administration of appropriate antibiotic therapy was 6.7 hours (0.0–23.3 hr). Linear regression analysis adjusting for severity of illness and comorbid conditions identified time to appropriate antibiotic therapy to be an independent determinant of postinfection ICU length of stay (0.095-d increase per hr of time to deliver appropriate antibiotic therapy; 95% CI, 0.057–0.132 d; p < 0.001) and postinfection hospital length of stay (0.134-d increase per hr of time to deliver appropriate antibiotic therapy; 95% CI, 0.074–0.194 d; p < 0.001). Other independent determinants associated with increasing ICU length of stay and hospital length of stay were mechanical ventilation (both ICU and hospital lengths of stay) and incremental peak WBC counts (hospital length of stay only). Incremental changes in severity of illness assessed by Acute Physiology and Chronic Health Evaluation II scores and comorbidity burden assessed by the Charlson comorbidity score were independently associated with decreases in ICU length of stay and hospital length of stay. Conclusions: We identified time to appropriate antibiotic therapy in patients with sepsis to be an independent determinant of postinfection ICU and hospital lengths of stay. Clinicians should implement local strategies aimed at timely delivery of appropriate antibiotic therapy to improve outcomes and reduce length of stay.

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case–control study

Critical Care 2015, 19:335

Gattarello S et al

Introduction: We aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000–2002 and 2008–2014, and the impact of the improvement in antibiotic strategies on outcomes. Methods: This was a matched case–control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000–2002 database (CAPUCI I group) were paired with 72 from the 2008–2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. Results: The most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1 %) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7 %); prevalence of shock was 59.7 %, while 73.6 % of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7 % versus 16.7 %; odds ratio (OR) 0.78, 95 % confidence interval (CI) 0.64–0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5 % in CAPUCI I and 92.7 % in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3 % and 37.5 versus 63.9 %; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95 % CI 0.07–0.74) and early antibiotic treatment (OR 0.07, 95 % CI 0.02–0.22) were independently associated with decreased intensive care unit mortality. Conclusions: In non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period.

The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-Analysis

The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock:A Systematic Review and Meta-Analysis
Critical Care Medicine: September 2015 - Volume 43 - Issue 9 - p 1907–1915

Sterling S, et al

Objectives: We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources: A comprehensive search criteria was performed using a predefined protocol. Study Selection: Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to emergency department triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or nonhuman studies. Data Extraction: Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of emergency department triage and 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds ratios were calculated using a random effect model. The primary outcome was mortality. Data Synthesis: A total of 1,123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from emergency department triage. Patients who received antibiotics more than 3 hours after emergency department triage (< 3 hr reference) had a pooled odds ratio for mortality of 1.16 (0.92–1.46; p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hr reference) had a pooled odds ratio for mortality of 1.46 (0.89–2.40; p = 0.13). There was no increased mortality in the pooled odds ratios for each hourly delay from less than 1 to more than 5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion: Using the available pooled data, we found no significant mortality benefit of administering antibiotics within 3 hours of emergency department triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence.

Does Appropriate Antibiotic Therapy Mean Only Adequate Spectrum and Timing?

Does Appropriate Antibiotic Therapy Mean Only Adequate Spectrum and Timing?
August 2015 - Volume 43 - Issue 8 - p 1773–1774

Lipman, J et al

Editorial placing some of the pharmokinetic responses of critically ill patients in context.

Minimizing antibiotic exposure in the ICU

Minimizing antibiotic exposure in the ICU: in search of the optimal strategy. Critical Care, Oct 2014, 18:613

Brun-Buisson, C.

http://ccforum.com/content/18/5/613

The current paradigm for antibiotic management in critically ill patients is to initiate broad-spectrum therapy followed by de-escalation based on microbiological results. Routine screening cultures may allow better targeting and reduce unnecessary exposure to antibiotics.

Optimal dosing of antibiotics in critically ill patients using continuous/extended infusions

Optimal dosing of antibiotics in critically ill patients using continous/extended infusions: A systematic review and meta-analysis.  Critical care, Dec 2013, Vol. 17(6), R279.

Chant, C., et al.

http://ccforum.com/content/17/6/R279/abstract

The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials such as extended/continuous infusions in critically ill patients is associated with improved outcomes as compared to traditional dosing methods.

Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia

Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: Impact on survival and bacterial resistance. Critical care, Nov 2013, Vol. 17(6), R:267.

Adrie, C., et al.

http://ccforum.com/content/17/6/R265/abstract

Several guidelines recommend initial empirical treatment with two antibiotics instead of one to decrease mortality in community-acquired pneumonia (CAP) requiring intensive-care-unit (ICU) admission. We compared the impact on 60-day mortality of using one or two antibiotics. We also compared the rates of nosocomial pneumonia and multidrug-resistant bacteria.

Mortality in ICU patients with bacterial community-acquired pneumonia: when antibiotics are not enough.

Intensive Care medicine

pp. 430-438
Mortality in ICU patients with bacterial community-acquired pneumonia: when antibiotics are not enough.
Rodriguez, A.; Lisboa, T.; Blot, S.; Martin-Loeches, I.; Solé-Violan, J.; Mendoza, D.; Rello, J.; Community-Acquired, P. I.
http://zetoc.mimas.ac.uk/wzgw?db=etoc&terms=RN245470731&field=zid

Antibiotics in the Intensive Care Unit : Focus on Agents for Resistant Pathogens

Author(s): Volles D . F . ; Branan T . N .
ISSUE: 2008 ; VOL 26 ; PART 3 (08-2008)
Access: Emergency Medicine Clinics of North America
Page: 813-834
Search the Web: [article] [author(s)]

Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit.

1. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Palmer-Lucy-B, Smaldone-Gerald-C, Chen-John-J, Baram-Daniel, Duan- Tao, Monteforte-Melinda, Varela-Marie, Tempone-Ann-K, O-Riordan- Thomas, Daroowalla-Feroza, Richman-Paul.
Critical care medicine, {Crit-Care-Med}, Jul 2008, vol. 36, no. 7, p. 2008-13, ISSN: 1530-0293.

CONTEXT: In critically ill intubated patients, signs of respiratory infection often persist despite treatment with potent systemic antibiotics. OBJECTIVE: The purpose of this study was to determine whether aerosolized antibiotics, which achieve high drug concentrations in the target organ, would more effectively treat respiratory infection and decrease the need for systemic antibiotics. DESIGN: Double-blind, randomized, placebo-controlled study performed from 2003 through 2004.

SETTING: The medical and surgical intensive care units of a university hospital.

PATIENTS: Critically ill intubated patients were randomized if: 1) > or = 18 yrs of age, intubated for a minimum of 3 days, and expected to survive at least 14 days; and 2) had ventilator-associated tracheobronchitis defined as the production of purulent secretions (> or = 2 mL during 4 hrs) with organism(s) on Gram stain. Of 104 patients monitored, 43 consented for treatment and completed the study. No patients were withdrawn from the study for adverse events.