Treatment Of Nosocomial Pneumonia Research Articles

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

BackgroundMultiple 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.MethodsWe 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.ResultsSixteen 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.ConclusionsThis 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

Extended Versus Intermittent Meropenem Infusion in the Treatment of Nosocomial Pneumonia: A Retrospective Single-Center Study.

The efficacy of extended meropenem infusions in patients with nosocomial pneumonia is not well defined. Therefore, we compared the clinical outcomes of extended versus intermittent meropenem infusions in the treatment of nosocomial pneumonia. We performed a retrospective analysis of extended versus intermittent meropenem infusions in adult patients who had been treated for nosocomial pneumonia at a medical ICU between 1 May 2018 and 30 April 2020. The primary outcome was mortality at 14 days. Overall, 64 patients who underwent an extended infusion and 97 with an intermittent infusion were included in this study. At 14 days, 10 (15.6%) patients in the extended group and 22 (22.7%) in the intermittent group had died (adjusted hazard ratio (HR), 0.55; 95% confidence interval (CI): 0.23-1.31; p = 0.174). In the subgroup analysis, significant differences in mortality at day 14 were observed in patients following empirical treatment with meropenem (adjusted HR, 0.17; 95% CI: 0.03-0.96; p = 0.045) and in Gram-negative pathogens identified by blood or sputum cultures (adjusted HR, 0.01; 95% CI: 0.01-0.83; p = 0.033). Extended infusion of meropenem compared with intermittent infusion as a treatment option for nosocomial pneumonia may have a potential advantage in specific populations.

Clinical effectiveness of tigecycline in combination therapy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective multi-centre observational study

BackgroundTigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU).MethodsThis multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents.ResultsWe analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p < 0.001) on day 28. In multivariate analysis, tigecycline treatment was a protective factor against clinical failure (PS-matched cohort: aOR 0.52, 95% CI 0.28–0.95) and all-cause mortality (original cohort: aHR 0.69, 95% CI 0.47–0.99; PS-matched cohort: aHR 0.47, 95% CI 0.30–0.74) at 28 days. Kaplan–Meier survival analysis in subgroups of patients suggested significant clinical benefits of tigecycline when added to a colistin-included (log rank p value 0.005) and carbapenem-included (log rank p value 0.007) combination regimen.ConclusionsIn this retrospective observational study that included ICU-admitted patients with nosocomial pneumonia caused by tigecycline-susceptible CR-GNB, mostly CRAB, tigecycline as part of a combination treatment regimen was associated with lower clinical failure and all-cause mortality rates.

Diagnosis, management and treatment of nosocomial pneumonia in ICU: a narrative review

Background and Objective: Despite recent advances in prevention, diagnosis, and treatment, hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are overriding among the most life-threatening infections in hospitalized patients and they may have serious consequences in term of clinical and economic burdens. This review will focus on current epidemiology, diagnosis and treatment of HAP/VAP.

Ceftolozane-tazobactam in nosocomial pneumonia.

Ceftolozane is a potent antimicrobial against Pseudomonas aeruginosa, including carbapenem-resistant and multidrug-resistant strains, and is also active against Enterobacteriaceae. It MIC (minimal inhibitory concentration) and MPC (mutant preventive concentration) are close together, allowing to avoid the mutant selection window specifically in the treatment of Pseudomonas aeruginosa infection. The molecule is time-dependent and stable when reconstituted at room temperature, facilitating safe and effective dosage optimization in frail and critically ill patients. It has been shown to be non-inferior to meropenem in the treatment of nosocomial infection in the ASPECT-NP study but superior in post-hoc studies in the subgroup of patients with ventilator-associated pneumonia, without the emergence of resistance during treatment. It is FDA approved at a dose of 3 g every 8 hours in the treatment of nosocomial pneumonia (HABP/VABP) in adults.

LB16. Surveillance Rates of Cefiderocol Heteroresistance Correlate With All-cause Mortality in the APEKS-NP and CREDIBLE-CR Trials

BackgroundCefiderocol is a recently FDA approved, novel siderophore beta-lactam antibiotic. Conventional antimicrobial susceptibility testing (AST) suggests that a variety of Gram-negative pathogens, including carbapenem-resistant (CR) isolates, are overwhelmingly susceptible to cefiderocol.. This antibiotic performed well in the APEKS-NP trial for the treatment of nosocomial pneumonia caused largely by carbapenem susceptible isolates. However, in the CREDIBLE-CR trial involving exclusively CR Gram-negative bacteria, cefiderocol was associated with a higher rate of all-cause mortality. We hypothesized one explanation for these discrepant data might be undetected cefiderocol heteroresistance (HR).HR is a form of antibiotic resistance in which an isolate harbors a minority resistant subpopulation of cells co-existing with a majority susceptible population, and is often undetected by standard AST. Isolates exhibiting undetected HR, with as low as 1 in 1 million resistant cells, can cause treatment failure in in vivo models.MethodsWe quantified HR to cefiderocol by population analysis profile (PAP) of 161 Acinetobacter, 180 Klebsiella, and 108 Pseudomonas isolates collected in Georgia, USA.ResultsWe observed CR isolates exhibited a high frequency of HR, which was largely undetected by standard AST, and correlated with all-cause mortality in the CREDIBLE-CR study (Table). Carbapenem-susceptible isolates exhibited no or low rates of cefiderocol HR (Table). Cephalosporin-resistant bacteria mostly exhibited increased rates of cefiderocol HR, but below those of CR strains. These differences in rates of cefiderocol HR correlated with the mortality data from the APEKS-NP and CREDIBLE-CR trials, across the bacterial species tested (Table).Table: Surveillance rates of cefiderocol heteroresistance correlate with all-cause mortality in the APEKS-NP and CREDIBLE-CR trials ConclusionThese data suggest that the lower rates of cefiderocol HR in carbapenem-susceptible isolates that predominated the APEKS-NP trial may explain the enhanced efficacy of the drug in that study as compared to the CREDIBLE-CR trial. Importantly, the widespread, undetected cefiderocol HR observed among CR pathogens may explain the discordance between this drug’s excellent in vitro susceptibility profile and increased patient mortality in the CREDIBLE-CR trial.Disclosures All Authors: No reported disclosures

1290. Ceftazidime-Avibactam Resistance Report in a Third Level Hospital in Mexico City

BackgroundThe surge of resistant Gram-negative organisms has been worrying infectious disease physicians and physicians in general because of the lack of a large number of antibiotics to which these organisms remain susceptible. Ceftazidime-Avibactam (CAZ-AVI) is a drug approved by the FDA to treat complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAIs) in combination with metronidazole, and recently for the treatment of nosocomial pneumonia. Worldwide resistance rates of Enterobacteriaceae to CAZ-AVI have been reported below 2.6%, and 4-8% for Pseudomonas aeruginosa. The FDA, CLSI, and EUCAST assigned the clinical breakpoints of susceptibility: MIC < /=8 mg/liter susceptible, and >/=8mg/liter, resistant. In Mexico, CAZ-AVI was approved in 2018, and its cost is very high compared to other antimicrobials, so its use is limited in very specific cases. The resistance rates to this antibiotic in the Mexican population remain largely unknown. MethodsWe tested 106 specimens for susceptibility to ceftazidime-avibactam using the disk Kirby-Bauer method. The inhibition zone diameter was determined in all cases and we considered the organism susceptible when the inhibition zone diameter was >=21 mm, and resistant with an inhibition zone diameter < = 20 mm. ResultsWe found 5 specimens (4.71%) resistant to ceftazidime-avibactam, corresponding to E. coli (3) and P. aeruginosa (2). Two of these were also resistant to colistin, and 4 to meropenem. All carbapenem-resistant isolates harbored Metallo-beta-lactamases genes, for E. coli was NDM gen, and for P. aeruginosa the VIM gene(GeneXpert® Cepheid). ConclusionThe ceftazidime-avibactam resistance among Gram-negative bacteria in our study is similar to the one reported in other international studies. We need more studies in our population to know the nationwide resistance to this antibiotic. Disclosures All Authors: No reported disclosures

Clinical Pharmacokinetics and Pharmacodynamics of Cefiderocol.

Cefiderocol is a new broad-spectrum cephalosporin antibiotic with promising activity against various Gram-negative bacteria including carbapenem-resistant strains. A chlorocatechol group in the C-3 side chain provides cefiderocol with a siderophore activity, improving its stability against β-lactamases and facilitating the transportation of cefiderocol across outer bacterial membranes. Cefiderocol shows linear pharmacokinetics over a broad range of clinically relevant doses, with unchanged renal excretion constituting the main route of elimination. Geometric means (coefficient of variation) of the volume of distribution and clearance in individuals with normal kidney function were 15.8 (15%) L and 4.70 (27%) L/h, respectively. In patients with end-stage renal disease, clearance was 1.10 (24%) L/h. Time above the minimum inhibitory concentration is the main predictor of efficacy. There is no evidence for clinically relevant interactions of cefiderocol with other drugs mediated by metabolizing enzymes or drug transporters. Simulations based on population pharmacokinetic modeling suggest that dosing regimens should be adjusted based on kidney function to optimize therapeutic exposure to cefiderocol. Clinical efficacy trials indicated that cefiderocol is non-inferior to imipenem/cilastatin in the treatment of complicated urinary tract infections and acute uncomplicated pyelonephritis, and to meropenem in the treatment of nosocomial pneumonia. In the one study currently available, cefiderocol performed similarly to the best available therapy in the treatment of severe carbapenem-resistant Gram-negative infections regarding clinical and microbiological efficacy. In summary, cefiderocol shows favorable pharmacokinetic/pharmacodynamic properties and an acceptable safety profile, suggesting that cefiderocol might be a viable option to treat infections with bacteria resistant to other antibiotics.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01063-5.

An evaluation of meropenem/vaborbactam for the treatment of nosocomial pneumonia

ABSTRACT Introduction: Nosocomial pneumonias are the second most common healthcare-associated infections (HCAIs), often associated with the presence of Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Acinetobacter species, and Enterobacter species. Increasing use of carbapenems has led to an increase in the prevalence of carbapenem-resistant gram-negative organisms, such as carbapenem-resistant Enterobacterales (CRE), P. aeruginosa (CRPA), and Acinetobacter baumannii (CRAB), limiting treatment options for patients at high-risk of multi-drug resistant (MDR) gram-negative pathogens. Areas covered: The purpose of this review is to discuss the role of meropenem/vaborbactam, a beta-lactam combined with a novel non-beta-lactam cyclic boronic acid beta-lactamase inhibitor (BLI), for the treatment of nosocomial pneumonia based on its chemistry, pharmacokinetics/dynamics, microbiological spectrum of activity, mechanisms of resistance, safety, and clinical efficacy. Expert opinion: Currently, any utilization of meropenem/vaborbactam beyond its FDA-approved indication for complicated urinary tract infections is considered off-label use; however, based on the pulmonary penetration of meropenem/vaborbactam, it is highly likely to be a safe and effective alternative to more toxic agents, like aminoglycosides and polymixins, for targeted therapy in pulmonary infections due to CRE. Unfortunately, the multifactorial resistance pattern of CRPA and other non-lactose-fermenting gram-negative bacteria restricts activity against these organisms which are common pathogens implicated in nosocomial pneumonia.

PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the ICU

Pneumonia is the leading infection-related cause of death. The use of simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials. What are the clinical criteria and contemporary epidemiology trends that are helpful in the identification of patients at high risk of nosocomial pneumonia? Within the ICUs of 28 US hospitals, we conducted a prospective cohort study among adults who had been hospitalized >48 hours and were considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients who experienced the development of nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures that are associated with increased risk of pneumonia development during the ICU admission. Between February 6, 2016, and October 7, 2016, 4,613 high-risk patients were enrolled. Among 1,464 high-risk patients (32%) who were treated for possible nosocomial pneumonia, 537 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures that are associated with increased risk of nosocomial pneumonia development (c-statistic, 0.709; 95%CI, 0.686-0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90days. Treatment for nosocomial pneumonia is common among patients in the ICU who are receiving high levels of respiratory support, yet more than one-half of patients who are treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk.

Pharmacoeconomic evaluation of ceftazidime + avibactam administration in the treatment of nosocomial pneumonia caused by carbapenem-resistant Enterobacteriacea and complicated by bacteremia

Pharmacoeconomic evaluation of ceftazidime + avibactam administration in the treatment of nosocomial pneumonia caused by carbapenem-resistant Enterobacteriacea and complicated by bacteremia

2227. Outcomes in Patients with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane–Tazobactam (C/T) Treatment of Nosocomial Pneumonia (ASPECT-NP)

BackgroundASPECT-NP, a phase 3, randomized, double-blind study, evaluated C/T (at double the approved dose for other indications) vs. meropenem (MEM) in adults with ventilated nosocomial pneumonia. We compared safety and efficacy outcomes from this trial among patients with and without renal impairment (RI).MethodsPatients were stratified by age and diagnosis and were randomized 1:1 to intravenous (IV) C/T 3 g every 8 h or IV MEM 1 g every 8 h. Study drug was administered for 8–14 days; doses were adjusted for moderate and severe RI. Eligible patients were mechanically ventilated; those on renal replacement therapy or with creatinine clearance (CrCL) < 15 mL/minute were excluded. Key efficacy endpoints included clinical cure rates at the test of cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) populations and Day 28 all-cause mortality (ACM) in the ITT population. In this analysis, patients were stratified based on renal function for outcome comparisons: normal renal function (CrCL ≥ 80 mL/minute); mild RI (CrCL > 50 to < 80 mL/minute); moderate RI (CrCL ≥ 30 to ≤ 50 mL/minute); and severe RI (CrCL ≥ 15 to < 30 mL/minute).ResultsA total of 726 patients were enrolled (C/T, N = 362; MEM, N = 364). Clinical cure rates at the TOC visit (CE and ITT populations) were robust across CrCL subgroups in both treatment arms and were similar based on 95% confidence intervals for treatment differences that included 0 (table). Day 28 ACM rates for patients with moderate and severe RI were numerically higher than those with mild RI in the MEM treatment arm. Rates of treatment-emergent adverse events (TEAEs) were similar in both treatment arms and across CrCL subgroups, with rates generally increasing with increasing RI severity. Rates of treatment-related TEAEs were low across treatment arms and CrCL subgroups with no treatment-related deaths reported.ConclusionSimilar clinical cure and Day 28 ACM rates at the TOC visit were found across treatment groups for all CrCL subgroups, consistent with the overall primary and key secondary efficacy results for the ASPECT-NP study. Both drugs were well-tolerated. The results of this analysis indicate that the use of dose-adjusted C/T is appropriate in patients with nosocomial pneumonia and moderate or severe RI. Disclosures All authors: No reported disclosures.

Perspectives on synthetic pharmacotherapy for the treatment of nosocomial pneumonia

ABSTRACTIntroduction: Nosocomial pneumonia is the second most common infection in hospital settings, resulting in substantial increases in morbidity, mortality, and length of hospital stay. The rapid increase in resistance of nosocomial pathogens to many antibiotics and the high dissemination of resistance genes highlight the need for innovative approaches to combat difficult-to-treat nosocomial respiratory infections.Areas covered: This review summarizes the synthetic antimicrobials that are currently in development for the treatment of nosocomial pneumonia, focusing on antibiotics in the final phases of clinical development and on the strategies employed by novel synthetic antimicrobial peptides.Expert opinion: Several novel synthetic antimicrobials are currently in the pipeline, and it appears that new antimicrobial peptides or mimetics will soon be made available, expanding the opportunities to treat nosocomial pneumonia. However, the approval process for use in the treatment of nosocomial pneumonia is arduous. Given that significant investments by pharmaceutical companies have ended in failure to obtain the approval of regulatory agencies, novel platforms for antimicrobial discovery are needed. The identification of new and fully synthetic chemical structures with activity against nosocomial pathogens needs to be followed by preclinical studies in large animals and by pharmacokinetic and pharmacodynamic studies in specific critically ill populations to assess lung penetration.

Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial

Nosocomial pneumonia is commonly associated with antimicrobial-resistant Gram-negative pathogens. We aimed to assess the efficacy and safety of ceftazidime-avibactam in patients with nosocomial pneumonia, including ventilator-associated pneumonia, compared with meropenem in a multinational, phase 3, double-blind, non-inferiority trial (REPROVE). Adults with nosocomial pneumonia (including ventilator-associated pneumonia), enrolled at 136 centres in 23 countries, were randomly assigned (1:1) to 2000 mg ceftazidime and 500 mg avibactam (by 2 h intravenous infusion every 8 h) or 1000 mg meropenem (by 30-min intravenous infusion every 8 h) for 7-14 days; regimens were adjusted for renal function. Computer-generated randomisation codes were stratified by infection type and geographical region with a block size of four. Participants and investigators were masked to treatment assignment. The primary endpoint was clinical cure at the test-of-cure visit (21-25 days after randomisation). Non-inferiority was concluded if the lower limit of the two-sided 95% CI for the treatment difference was greater than -12·5% in the coprimary clinically modified intention-to-treat and clinically evaluable populations. This trial is registered with ClinicalTrials.gov (NCT01808092) and EudraCT (2012-004006-96). Between April 13, 2013, and Dec 11, 2015, 879 patients were randomly assigned. 808 patients were included in the safety population, 726 were included in the clinically modified intention-to-treat population, and 527 were included in the clinically evaluable population. Predominant Gram-negative baseline pathogens in the microbiologically modified intention-to-treat population (n=355) were Klebsiella pneumoniae (37%) and Pseudomonas aeruginosa (30%); 28% were ceftazidime-non-susceptible. In the clinically modified intention-to-treat population, 245 (68·8%) of 356 patients in the ceftazidime-avibactam group were clinically cured, compared with 270 (73·0%) of 370 patients in the meropenem group (difference -4·2% [95% CI -10·8 to 2·5]). In the clinically evaluable population, 199 (77·4%) of 257 participants were clinically cured in the ceftazidime-avibactam group, compared with 211 (78·1%) of 270 in the meropenem group (difference -0·7% [95% CI -7·9 to 6·4]). Adverse events occurred in 302 (75%) of 405 patients in the ceftazidime-avibactam group versus 299 (74%) of 403 in the meropenem group (safety population), and were mostly mild or moderate in intensity and unrelated to study treatment. Serious adverse events occurred in 75 (19%) patients in the ceftazidime-avibactam group and 54 (13%) patients in the meropenem group. Four serious adverse events (all in the ceftazidime-avibactam group) were judged to be treatment related. Ceftazidime-avibactam was non-inferior to meropenem in the treatment of nosocomial pneumonia. These results support a role for ceftazidime-avibactam as a potential alternative to carbapenems in patients with nosocomial pneumonia (including ventilator-associated pneumonia) caused by Gram-negative pathogens. AstraZeneca.

Retrospective View on Clinical Aspects and Treatment of Nosocomial Pneumonia

The problem of nosocomial pneumonia (NP) development and multidrug-resistant pathogens increase dictates the need of studies to optimize antibiotic therapy and possible combined usage of inhaled antibiotics. We retrospectively reviewed all medical records of surgical patients (n=700) in a multidisciplinary hospital for one year (2014-15). NP was assessed according to the criteria of American Thoracic Society. Demographic, risk factors, microbiological monitoring were analyzed. Statistical analysis was performed with R version 3.3.2. In patients the incidence of NP was 17.1% (women - 46.7%, men - 53.3%, mean age 63.4 years ± 13.4 (sd)). Cancer strongly affected adverse outcome (53%; p=0.003). The median Simplified Acute Physiology Score (SAPS II) was 39. BMI didn’t differ significantly between outcome groups (27.0 ± 4.7 vs 26.8 ± 5.7; p=0.88). Tracheostomy patients died more frequently (60%; p=6.964e-11). The duration of mechanical ventilation in groups with adverse and favorable outcome was 13.5 [7-26.3] and 1 day [0-6.4] accordingly (p=4.934e-08). NP development in groups with adverse and favorable outcome was - 11.5 [7-15] and 12 [7-15] days (p=0.9). According to microbiological results gram-negative organisms dominated: Acinetobacter baumanii KPC (14.5%), Klebsiella pneumoniae extended spectrum beta lactam (ESBL) (21.7%), Klebsiella pneumoniae carbapenemases (KPC) producing bacteria (9.5%), Ps aeruginosa KPC (10.5%). Surprisingly in patients with inhalation therapy lower survivance (48%) was observed comparing with those who didn’t receive it (72% p = 0.03). Gram-negative resistant organisms prevalent in nosocomial pneumonia development, which causes high mortality in the ICU department. Our results are controversial considering current investigations. Further investigations are required.

CHANGES OF INTERLEUKINS IN PATIENTS WITH NOSOCOMIAL PNEUMONIA AGAINST A BACKGROUND OF TRAUMATIC BRAIN INJURY: ROLE IN THE DIAGNOSIS AND MONITORING OF DISEASE

Introduction. Nosocomial pneumonia (NP) is the second leading frequency and mortality among nosocomial infections. NP is a frequent complication of severe traumatic brain injury (TBI). The difficulty in diagnosis and monitoring of disease NP on the background of TBI is that the usual signs NP "masked" manifestations of the underlying disease. The aim of our study was to improve the diagnosis and assess the effectiveness of the treatment of nosocomial pneumonia with clarithromycin by studying of serum interleukins in patients with nosocomial pneumonia on the background of traumatic brain injury. Materials and methods. We determined levels of TNFα, IL-4, IL-6, IL-8, IL-10. We examined 45 patients with isolated TBI, 44 patients with NP (standard treatment scheme), 49 patients with NP, each therapy with clarithromycin. The control group was 33 relatively healthy people. Conclusions. The study revealed a significant increase in the concentration of interleukin TNFα, IL-6, IL-8, IL-10 in the serum of patients with NP on the background of TBI compared with patients with isolated TBI and healthy individuals. Our study found significantly lower concentrations of interleukin TNFα, IL-6, IL-8, IL-10 in the serum of patients after treatment with the addition of clarithromycin compared with patients with standard therapy.

Treatment of multi drug resistant gram negative bacilli with inhaled polymyxin-b

Introduction: A major challenge has arisen regarding the treatment of infections caused by Gram-negative bacilli, particularly those with high level intrinsic resistance to many antibiotic classes and extreme ability to acquire resistance. Aim: The present study was conducted to assess the safety and efficacy of aerosolized polymyxin-B in comparison to intravenous polymyxin-B therapy for treatment of MDR GNB. Materials and methods: Study was performed over a period of 18 months. A Comparative two group randomized clinical study with 50 patients with 25 patients in Group A and 25 patients in Group-B is undertaken to study the outcome of therapy, fever response to therapy and side effects. Results: Mean duration of ICU stay was 28.68±9.15 days in Group-A while it was 31.64±9.16 days in Group-B. This was not statistically significant with p-value 0.258786. Pseudomonas aeruginosa is the most common organism isolated .In this study improvement, cure and failure rates were 44%, 44% and 12% respectively in Group-A(inhaled polymyxin b). while improvement,cure and failure rates were 40%,20% and 40% in Group-B(iv Polymyxin B) which was statistically significant. fever response to study was better in Group-A (inhaled polymyxin B) which was statistically significant. Adverse events to polymyxin B Inhalation (bronchospasm) occurred in 16% of the patients in group-A , Nephotoxicity in 28% of patients in group –B.but did not lead to suspension of treatment. Conclusion: Inhaled polymyxin-B was useful in treatment of nosocomial pneumonia caused by MDR-GNB in mechanically ventilated patients. As the drug is given by inhalational route systemic side effects can be minimized.

Pharmacodynamics, pharmacokinetics and clinical efficacy of telavancin in the treatment of pneumonia

ABSTRACTIntroduction: Telavancin is a novel lipoglycopeptide derivative of vancomycin that has activity against Gram-positive aerobic and anerobic bacteria, for the treatment of serious infections, including complicated skin and skin structure infections (cSSSI) and pneumonia.Areas covered: This article was compiled through searches on telavancin up to December 2015 in the PubMed and the clinicaltrials.gov databases; the FDA and European Medicine Agency (EMA) websites. In our review, particular attention was paid to those articles that reviewed the pharmacokinetic characteristics of the drug and animal models of infection. We also searched for evidence of the efficacy of telavancin as demonstrated in clinical trials, safety and tolerability data and have compiled a summary of clinical trials on telavancin in pneumonia.Expert opinion: Telavancin is approved in Europe and the USA for the treatment of nosocomial pneumonia caused by methicillin resistant Staphylococcus aureus when other alternatives are not suitable.

Severe pneumonia in the intensive care unit

Pneumonia has a high morbidity and mortality and is responsible for significant healthcare costs. In Germany, two evidence-based recommendations for the treatment of pneumonia are available: the S3 Guideline for Prevention, Diagnosis and Treatment of Adult Patients with Community-acquired Pneumonia and the S3Guideline on Epidemiology, Diagnosis and Treatment of Nosocomial Pneumonia. On this basis, individualised patient management as shown in this article may be established.

Prolonged versus Intermittent Infusion of β-Lactams for the Treatment of Nosocomial Pneumonia: A Meta-Analysis.

BackgroundThe primary objective of this meta-analysis is aimed at determining whether β-lactams prolonged infusion in patients with nosocomial pneumonia (NP) results in higher cure rate and improved mortality compared to intermittent infusion.Materials and MethodsRelevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL from inception to September 1st, 2015. All published articles which evaluated the outcome of extended/continuous infusion of antimicrobial therapy versus intermittent infusion therapy in the treatment of NP were reviewed.ResultsA total of ten studies were included in the analysis involving 1,051 cases of NP. Prolonged infusion of β-lactams was associated with higher clinical cure rate (OR 2.45, 95% CI, 1.12, 5.37) compared to intermittent infusion. However, there was no significant difference in mortality (OR 0.85, 95% CI 0.63–1.15) between the two groups. Subgroup analysis for β-lactam subclasses and for severity of illness showed comparable outcomes.ConclusionThe limited data available suggest that reduced clinical failure rates when using prolonged infusions of β-lactam antibiotics in critically ill patients with NP. More detailed studies are needed to determine the impact of such strategy on mortality in this patient population.