Antibiotic Therapy For Ventilator-associated Pneumonia Research Articles

OPTIMIZATION OF EMPIRICAL ANTIBACTERIAL THERAPY OF VENTILATOR-ASSOCIATED PNEUMONIA, INDUCED BY GRAM-NEGATIVE MULTIRESISTANT STRAINS

Introduction: Ventilator-associated pneumonia is one of the most common healthcare associated infections, arising in the ICU. The greatest difficulty is presented by patients, whose infection is caused by gram-negative multidrug-resistant strains. That is why empirical antibacterial therapy of ventilator-associated pneumonia requires optimization and improvement.
 Aim of study: To compare the effectiveness of two schemes of empirical antibacterial therapy of ventilator-associated pneumonia, based on carbapenems, aminoglycosides and monobactams.
 Materials and methods: This is randomized controlled monocentral study, which included 64 patients older than 18 years, who have developed ventilator- associated pneumonia during long-term mechanical ventilation.
 Results: The use of combination of meropenem and aztreonam as an empirical antibiotic therapy of ventilator-associated pneumonia was accompanied by a significant increase of oxygenation indexes, effective purification of sputum from microorganisms, decrement of resistance and superinfection development in comparing with patients with traditional scheme empiric antibacterial therapy. The recommended scheme is also safe in nephrotoxicity context.
 Conclusion: The use as an empirical antibacterial therapy of ventilator-associated pneumonia the combination of meropenem and aztreonam was accompanied by significant decrement of length of mechanical ventilation and significant reduction of ICU-stay. The mortality levels were also less in investigation group compared with the group with traditional scheme of empirical antibacterial therapy.

Evaluating antibiotic therapy for ventilator-associated pneumonia caused by gram-negative bacilli

IntroductionVentilator-associated pneumonias (VAPs) are a complication of mechanical ventilation in the intensive care unit (ICU) that increase length of stay, morbidity, and mortality. While identifying and treating infections early is paramount to improving patient outcomes, more and more data demonstrate limited courses of antibiotics improve outcomes. Prolonged (10–14 day) courses of antibiotics have remained the standard of care for pneumonia due to gram-negative bacilli (GNR). We aimed to review our GNR VAPs to assess risk factors for recurrent GNR infections. MethodsWe reviewed trauma patients who developed VAP from 02/2019 through 05/2022. Demographics, injury characteristics, and outcomes were reviewed with a focus on pneumonia details including the cultured pathogen(s), antibiotic(s) used, treatment duration, and presence of recurrent infections. We then compared single episode VAPs to multiple episode VAPs among patients infected by GNRs. ResultsEleven of the fifty trauma patients admitted to the ICU suffered a VAP caused by a GNR. Of these eleven patients, six experienced a recurrent infection, four of which were caused by Pseudomonas aeruginosa and two of which were caused by Enterobacter aerogenes. Among the patients who received ten days of antibiotic treatment, half suffered a recurrence. Although, there was no difference in the microbiology or antibiotic duration between the recurrences and single episodes. ConclusionDespite prolonged use of antibiotics, we found that the risk of recurrent or persistent infections was high among patients with VAP due to GNB. Further study is needed to determine optimal treatment to minimize the risk of these recurrences. Key messageVentilator-associated pneumonia due to gram-negative bacilli is a rare but high morbidity complication in intensive care units. Despite prolonged duration of therapy, these infections still appear to account for many recurrent infections and further study into optimal therapy is warranted.

Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii: A Real Life, Prospective, Observational, Single-Center Study.

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64-78) vs. 62 (IQR 52-69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6-8) vs. 4 (IQR 2-6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9-11) vs. 9 (IQR 7-11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04-1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19-0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17-0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option.

Which trial do we need? Comparison of 7 versus 14 days of antibiotic therapy for ventilator-associated pneumonia due to highly resistant gram-negative bacteria

Which trial do we need? Comparison of 7 versus 14 days of antibiotic therapy for ventilator-associated pneumonia due to highly resistant gram-negative bacteria

Comparison of a short versus long-course antibiotic therapy for ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials

For ventilator-associated pneumonia (VAP), the safety of short-course versus long-course antibiotic therapy is still debated, especially regarding documented VAP due to non-fermenting Gram-negative bacilli (NF-GNB). The aim of this meta-analysis was to assess the rates of recurrence and relapse of VAP in patients receiving short-course (≤8 days) and long-course (≥10-15 days) of antibiotic therapy. The protocol for this study was registered in the PROSPERO database (ID: CRD42022365138). We performed an electronic search of the relevant literature and limited our search to data published from 2000 until September 1, 2022. We searched for randomized controlled trials (RCTs) in the United States National Library of Medicine, Cochrane Database of Systematic Reviews (CDSR) and the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, National Institutes of Health PubMed/MEDLINE, web of science and Google Scholar databases. The primary endpoint was the recurrence and relapses of VAP, secondary endpoints were 28-day mortality, mechanical ventilation duration, number of extra-pulmonary infections and length of ICU stay. We identified five relevant studies involving 1069 patients (530 patients in the short-course group and 539 patients in the long-course group). The meta-analysis did not reveal any significant difference between short and long-course antibiotic therapy for recurrence and relapses of VAP (odd ratio "OR"=1.48, 95% confidence intervals (CI) [0.96, 2.28], p=0.08 and OR=1.45, 95% CI [0.94, 2.22], p=0.09, respectively), including those due to NF-GNB (OR=1.90, 95% CI [0.93, 3.33], p=0.05 and OR=1.76, 95% CI [0.93, 3.33], p=0.08, respectively). No difference was found for 28 days-mortality (OR=1.24, 95% CI [0.92, 1.67], p=0.16), mechanical ventilation duration, number of extra-pulmonary infections and length of ICU stay. However, short-course therapy significantly increased the number of antibiotic-free days. Our meta-analysis showed that short-course antibiotic therapy did not result in increased number of recurence and relapses of VAP, suggesting that short-course should be preferred to reduce the exposure to antibiotics. None.

Comparison of 8 versus 15days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial.

Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8days) vs. prolonged antibiotic therapy (15days) in VAP due to PA (PA-VAP). We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8days) or a long-duration treatment (15days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90days. The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay. Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.

The role of lung ultrasound in procalcitonin-guided antibiotic discontinuation in ventilator-associated pneumonia.

ABSTRACTBackground and Aims:Starting antibiotic therapy at the proper time is the cornerstone of the management of ventilator-associated pneumonia (VAP). However, using antibiotics for a long duration of therapy in intensive care leads to increased bacterial resistance, financial burden and adverse drug reactions. We hypothesised that lung ultrasound may have a role in guiding antibiotic discontinuation in patients with VAP that will help to reduce the antibiotic duration and decrease the resistance.Methods:This was a prospective blinded cohort study from October 2020 to September 2021 in which 62 VAP patients were recruited. Antibiotics were started, procalcitonin (PCT) level and clinical pulmonary infection score were estimated and lung ultrasound (US) was performed on day 1 and repeated on day 7. On day 7, discontinuation of antibiotics was recommended if the PCT level was <0.25 μg/L. A lung reaeration score was recorded.Results:Based on the PCT levels, antibiotics were discontinued in 40 patients. The computed tomography findings of VAP had improved in all. The ultrasound reaeration score showed a highly significant negative correlation with the PCT on day 7 (-0.718, P < 0.001). A cut-off of 5 for the US score showed a sensitivity of 92.5%, specificity of 95.5%, positive predictive value of 97.4% and negative predictive value of 87.5% in detecting a low PCT score on day 7.Conclusion:Lung US is a non-invasive and safe method that can be used to guide antibiotic therapy in VAP.

Effectiveness and safety of adjunctive inhaled antibiotics for ventilator-associated pneumonia: A systematic review and meta-analysis of randomized controlled trials.

The efficacy and safety of adjunctive inhaled antibiotic therapy for ventilator-associated pneumonia (VAP) was systematically reviewed based on updated studies. We searched four databases and four clinical trial registration platforms to identify relevant studies published prior to May 19, 2020. Randomized controlled trials (RCTs) assessing adjunctive antibiotic inhalation treatment for VAP patients were eligible for this review. Two reviewers independently screened the articles and extracted the data. Information on inhaled therapy and clinical outcomes was collected. Study quality was assessed with the Cochrane risk of bias tool. The meta-analysis was conducted with Review Manager and R software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines were used to evaluate the quality of evidence for each pooled outcome. Eleven RCTs and 1210 patients were included in this analysis after the application of the inclusion and exclusion criteria. Compared with the use of intravenous injection alone, the use of adjunctive inhaled antibiotic therapy improved the rates of clinical cure (relative risk (RR) 1.13, 95% CI [1.02,1.26]) and microbiological eradication (RR 1.45, 95% CI [1.19,1.76]) in VAP patients. However, despite these improvements, mortality was not reduced (RR 1.00, 95% CI [0.82,1.21]). Adjunctive antibiotics delivered through the respiratory tract were not associated with a higher risk of renal impairment but were associated with an increased risk of bronchospasm (RR 2.74, 95% CI [1.31,5.73] during treatment. Adjunctive inhaled antibiotics improved the clinical outcomes in VAP patients, but the increased rates clinical cure and microbiological eradication were not associated with reduced mortality. The use of nebulized antibiotics is not supported by the currently available evidence as a routine therapeutic strategy for VAP. CRD42020186970.

Antibiotics for ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality, complicating the medical course of approximately 10% of mechanically-ventilated patients, with an estimated attributable mortality of 13%. To treat VAP empirically, the American Thoracic Society currently recommends antibiotic therapy based on the patients' risk of colonisation by an organism with multidrug resistance. The selection of initial antibiotic therapy in VAP is important, as inappropriate initial antimicrobial treatment is associated with higher mortality and longer hospital stay in intensive care unit (ICU) patients.While guidelines exist for the antibiotic treatment of hospital-acquired pneumonia (HAP) from the American Thoracic Society and the British Society for Antimicrobial Chemotherapy, there are many limitations in the quality of available evidence. This systematic review aimed to summarise the results of all randomised controlled trials (RCTs) that compare empirical antibiotic regimens for VAP. The primary objective of this review was to assess the effect of different empirical antimicrobial therapies on the survival and clinical cure of adult patients with ventilator-associated pneumonia (VAP). Secondary objectives included reporting the incidence of adverse events, new superinfections, length of hospital stay, and length of intensive care unit (ICU) stay associated with these therapies. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CINAHL and Web of Science to December 2015; we searched ClinicalTrials.gov to September 2016. Two review authors independently assessed RCTs comparing empirical antibiotic treatments of VAP in adult patients, where VAP was defined as new-onset pneumonia that developed more than 48 hours after endotracheal intubation. Physicians and researchers were not required to be blinded for inclusion in this review. Two review authors independently extracted study data. We pooled studies and analysed them in two ways. We examined monotherapy, or a single experimental antimicrobial drug, versus combination therapy, or multiple experimental antimicrobial drugs. We also examined carbapenem therapy versus non-carbapenem therapy. We included 12 studies with 3571 participants. All included studies examined the empiric use of one antimicrobial regimen versus another for the treatment of adults with VAP, but the particular drug regimens examined by each study varied. There was potential for bias because some studies did not report outcomes for all participants. All but one study reported sources of funding or author affiliations with pharmaceutical companies.We found no statistical difference in all-cause mortality between monotherapy and combination therapy (N = 4; odds ratio (OR) monotherapy versus combination 0.97, 95% confidence interval (CI) 0.73 to 1.30), clinical cure (N = 2; OR monotherapy versus combination 0.88, 95% CI 0.56 to 1.36), length of stay in ICU (mean difference (MD) 0.65, 95% CI 0.07 to 1.23) or adverse events (N = 2; OR monotherapy versus combination 0.93, 95% CI 0.68 to 1.26). We downgraded the quality of evidence for all-cause mortality, adverse events, and length of ICU stay to moderate for this comparison. We determined clinical cure for this comparison to be of very low-quality evidence.For our second comparison of combination therapy with optional adjunctives only one meta-analysis could be performed due to a lack of trials comparing the same antibiotic regimens. Two studies compared tigecycline versus imipenem-cilastatin for clinical cure in the clinically evaluable population and there was a statistically significant increase in clinical cure for imipenem-cilastatin (N = 2; OR tigecycline versus imipenem-cilastatin 0.44, 95% CI 0.23 to 0.84). Of importance, this effect was due to a single study.We found no statistical difference in all-cause mortality between carbapenem and non-carbapenem therapies (N = 1; OR carbapenem versus non-carbapenem 0.59, 95% CI 0.30 to 1.19) or adverse events (N = 3; OR carbapenem versus non-carbapenem 0.78, 95% CI 0.56 to 1.09), but we found that carbapenems are associated with a statistically significant increase in the clinical cure (N = 3; OR carbapenem versus non-carbapenem 1.53, 95% CI 1.11 to 2.12 for intention-to-treat (ITT) analysis and N = 2; OR carbapenem versus non-carbapenem 2.29, 95% CI 1.19 to 4.43 for clinically evaluable patients analysis). For this comparison we downgraded the quality of evidence for mortality, and clinical cure (ITT and clinically evaluable populations) to moderate. We determined the quality of evidence for adverse events to be low. We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug-resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta-analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP.Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics.

An Argument for the Use of Aminoglycosides in the Empiric Treatment of Ventilator-Associated Pneumonia.

Appropriate empiric antibiotic therapy for ventilator-associated pneumonia improves outcomes. Controversy exists regarding the inclusion of aminoglycosides in empiric therapeutic regimens. The Ovid and Cochrane databases were searched for relevant literature regarding the use of aminoglycosides in combination therapy for ventilator-associated pneumonia. The data supporting the use of aminoglycosides in certain populations and strategies to limit toxicity are summarized. In patients at high risk of infection with antibiotic-resistant gram-negative bacilli and in those with severe illness, aminoglycosides improve clinical outcomes. In critically ill populations, short-duration therapy and high-dose extended-interval dosing of aminoglycosides can improve therapeutic efficacy while limiting nephrotoxicity. In selected populations using appropriate dosing strategies, aminoglycosides should be considered for empiric treatment of ventilator-associated pneumonia.

Impact of imipenem and amikacin pharmacokinetic/pharmacodynamic parameters on microbiological outcome of Gram-negative bacilli ventilator-associated pneumonia.

Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004). In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary.

Development of antibiotic treatment algorithms based on Gram stain to restrict use of broad-spectrum antibiotics in the treatment of ventilator-associated pneumonia: a retrospective analysis

Ventilator-associated pneumonia (VAP) is a common and serious problem in ICUs. Several studies have been conducted to determine the effectiveness of Gram stain of tracheal aspirates for diagnosing VAP. However, the effectiveness for predicting causative microorganisms and guiding appropriate initial antibiotic therapy has not been evaluated. The purpose of this study is to determine whether Gram stain of tracheal aspirates can guide appropriate initial antibiotic therapy for VAP.

Performance and impact of a rapid method combining mass spectrometry and direct antimicrobial susceptibility testing on treatment adequacy of patients with ventilator-associated pneumonia

Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. Using broad-spectrum antibiotics for 48 h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Performing AST directly on clinical respiratory samples would hasten the process by at least 24 h. Here, we analysed the diagnostic performance of a rapid method combining mass spectrometry and direct AST (DAST), and compared it with the conventional method (mass spectrometry with conventional AST (CAST)). Additionally, we assessed its potential impact on antimicrobial use in patients. Over a period of 18 months, the two methods were performed on 85 bronchoalveolar lavages obtained from intensive care unit patients with suspected VAP, and in which Gram-negative bacilli were observed on direct examination. Only the CAST results were reported to the clinicians. DAST produced useable results in 85.9% of the patients. The sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1%, (95% CI 93.3–101) and 97.4% (93.7–101), respectively) and amikacin (88.9% (81.7–96.1) and 96.4% (92.1–100.7), respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2–91.5) to 100%, and from 86.4 (78.5−94.2) to 100%, respectively. If the DAST results had been reported to the clinicians, treatment could have been optimized 24 h earlier in 35/85 (41.2%) patients, with 17 carbapenem patient-days saved. Overall, routine use of the DAST method could help optimize earlier antibiotic treatment in patients with suspected VAP.

The adequacy of timely empiric antibiotic therapy for ventilator-associated pneumonia: An important determinant of outcome

ObjectiveThe individual impact of timeliness vs adequacy of empiric antibiotic therapy for a clinical suspicion of ventilator-associated pneumonia (CSVAP) is unknown. Accordingly, in patients with CSVAP and timely initiation of empiric antibiotic therapy, we determined the impact of inadequate therapy (IT). MethodsAnalysis of a randomized trial of CSVAP treated empirically with meropenem or meropenem plus ciprofloxacin was done. Adequate therapy (AT) was considered present if all pathogens in the index culture were sensitive to the empiric antibiotics; IT was defined as the presence of pathogens resistant to the empiric antibiotics. A priori, for Pseudomonas sp, 2 antibiotics with activity against the organisms were required for AT to be considered present. ResultsOf 739 patients with CSVAP, 350 had positive cultures: 313 (89.4%) had AT, and 37 (10.6%), IT. The IT group had higher intensive care unit (35.1% vs 11.8%, P = .0001) and hospital mortalities (48.7% vs 19.5%, P < .0001), increased mechanical ventilation (15.8 vs 6.8 days, P = .0005), intensive care unit stay (13.5 vs 8.4 days, P = .02), and hospital stay (42.2 vs 27.9 days, P = .04). In multivariate analysis and a separate case control analysis, the odds ratio of hospital mortality with IT was 3.05 (95% confidence interval, 1.25-7.45; P = .01) and 3.00 (95% confidence interval, 1.24-7.24; P = .01), respectively. ConclusionIn the context of early administration of empiric broad spectrum antibiotics for CSVAP, IT is associated with higher morbidity and mortality.

Does De-Escalation of Antibiotic Therapy for Ventilator-Associated Pneumonia Affect the Likelihood of Recurrent Pneumonia or Mortality in Critically Ill Surgical Patients?

Does De-Escalation of Antibiotic Therapy for Ventilator-Associated Pneumonia Affect the Likelihood of Recurrent Pneumonia or Mortality in Critically Ill Surgical Patients?

Duration of Antibiotic Therapy for Ventilator-Associated Pneumonia in Burn Patients

Duration of Antibiotic Therapy for Ventilator-Associated Pneumonia in Burn Patients

Changes in Pulmonary Cytokines during Antibiotic Therapy for Ventilator-Associated Pneumonia

A major unanswered question in ventilator-associated pneumonia (VAP) management relates to patient response to therapy. We investigated the use of pulmonary cytokines as biomarkers for response to antibiotic therapy for VAP. Prospective, observational pilot study of 12 critically ill trauma patients with VAP using a bronchoscopic bronchoalveolar lavage (BAL) (> or =100,000 colony-forming units [cfu]/mL). All patients underwent repeat BAL after three days of adequate antibiotic therapy. Changes in pulmonary effluent interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha concentrations measured on diagnostic and repeat BAL were evaluated on the basis of the presence of a microbiologic response (<10,000 cfu/mL on repeat BAL). Six post-therapy BAL samples showed a microbiologic response. In responders, IL-8 and TNF-alpha concentrations decreased significantly (1,303 +/- 1,150 ng/mL in diagnostic BAL sample vs. 309 +/- 448 ng/mL after response; p = 0.08 and 9.9 +/- 18.4 ng/mL in diagnostic vs. 0.1 +/- 0.1 ng/mL in post-treatment sample; p = 0.06, respectively). In non-responders, IL-8 (449 +/- 426 ng/mL vs. 326 +/- 319 ng/mL; p = 0.59) and TNF-alpha (1.2 +/- 1.9 ng/mL vs. 0.3 +/- 0.3 ng/mL; p = 0.31) did not change significantly. Clinical response measures did not change or increased in responders, whereas these parameters did not change or decreased paradoxically in non-responders. This pilot study indicates pulmonary concentrations of IL-8 and TNF-alpha decrease in microbiologic responders with VAP. Conversely, clinical response parameters were discordant with the microbiologic response. The utility of pulmonary cytokine behavior in evaluating the effectiveness of antibiotic therapy for VAP should be studied further.

Re: Does De-Escalation of Antibiotic Therapy for Ventilator-Associated Pneumonia Affect the Likelihood of Recurrent Pneumonia or Mortality in Critically Ill Surgical Patients?

The Journal of Trauma: Injury, Infection, and Critical Care: November 2009 - Volume 67 - Issue 5 - p 1133-1134 doi: 10.1097/TA.0b013e3181bbf56f

Concerns Regarding the Methodology of the Study Entitled “Does De-Escalation of Antibiotic Therapy for Ventilator-Associated Pneumonia Affect the Likelihood of Recurrent Pneumonia or Mortality in Critically Ill Surgical Patients?”

Suzuki, Hikaru Medical Student; Kagawa, Hiroki MD; Iwata, Kentaro MD, MSc, FACP, FIDSA Author Information

Determining treatment effectiveness and period of treatment

Judging the effect of treatment for hospital-acquired pneumonia is difficult using only inflammatory parameters or findings from chest radiography. Preferably, treatment effects should be judged comprehensively from body temperature, findings of chest radiography, inflammatory parameters, status of purulent discharge, bacteriological findings and oxygenation. In VAP, the parameter most closely correlated with prognosis is trend in PaO(2)/FiO(2). Clinical improvements are normally seen within 72 h. Antimicrobials thus should not be changed until the third day unless a dramatic deterioration in symptoms is seen. With the exception of pneumonia from microbes that tend to possess strong resistance, such as Pseudomonas aeruginosa, a treatment period of 7-10 days is adequate if the early-stage drugs are effective. If no improvements in the course are achieved by 3 days after starting treatment, an investigation should be made into whether treatment should be continued or changed to a different antimicrobial agent.