Treatment Of Hospital-acquired Pneumonia Research Articles

Population pharmacokinetics and exposure-response analysis of tigecycline in patients with hospital-acquired pneumonia.

Tigecycline has been widely used to treat hospital-acquired pneumonia (HAP) off-label since it is effective against a wide range of multidrug-resistant bacteria. However, no recommended dosage for this indication has been evaluated, resulting in possible inadequate treatment. The aims of this study are to establish the population pharmacokinetic (PPK) model of tigecycline in Chinese patients with HAP, as well as to evaluate the exposure-response relationship for the treatment of HAP with multidrug-resistant gram-negative bacteria. A PPK analysis of tigecycline was conducted on pooled data from 328 blood samples obtained from 89 patients with HAP. Tigecycline plasma concentrations were measured by a two-dimensional liquid chromatographic system and the data were analysed using Phoenix NLMETM software. Exposure-response analyses for efficacy were performed based on the data from 79 HAP patients with multidrug-resistant gram-negative infections. Classification and regression tree and logistic regression analyses were employed to identify which pharmacokinetic-pharmacodynamic (PK-PD) indices and magnitudes were the significant predictors of tigecycline efficacy. A two-compartment model with zero-order absorption and first-order elimination adequately described the data. A larger body weight was associated with increased central volume of distribution and clearance (P<.005), and increased age, baseline creatinine concentration and aspertate aminotransferase were associated with decreased clearance (P<.005). The AUC0-12h ×V/MIC ratio, APACHEII score and combined Pseudomonas aeruginosa infection are the strong predictors for tigecycline clinical response. Classification and regression tree analyses indicated that the combination of APACHEII score < 24 and AUC0-12h ×V/MIC ratio≥100 was associated with clinical success. The proposed PPK model may serve as the basis for estimating tigecycline exposure for PK-PD analyses, and the PK-PD index and magnitude found in this study could be used for designing proper dosage regimens of tigecycline.

Issues in antibiotic therapy for hospital-acquired and ventilator-associated pneumonia: emerging concepts to improve outcomes

ABSTRACT Introduction:Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) result in significant morbidity and mortality. The emergence of multi-drug resistant organisms has complicated the matter, as many of these pathogens now represent key causes of VAP and HAP. While anumber of new medications have been approved, acomprehensive appreciation of pharmacokinetic and pharmacodynamic principles, which, are often neglected, is key to effective treatment. Areas covered: The authors discuss the central pharmacokinetic and pharmacodynamic principles underlying antibiotic utilization, especially as they pertain to the treatment of VAP and HAP. They further address the concept of and implications of augmented renal clearance for the patient with nosocomial pneumonia. Finally, the authors review the evolving data on colistin and inhaled antibiotics in the management of pneumonia. Expert opinion: An enhanced understanding of the pharmacokinetic and pharmacodynamic principles along with insight into the concept of augmented renal clearance can help guide drug development and improve the way we currently dose and deliver most antibiotics. There is now mounting data on the limited efficacy and substantial nephrotoxicity of colistin, which makes it difficult to justify its continued use. While the concept of inhaled antibiotics is enticing, we lack conclusive data proving the efficacy of this paradigm.

Carbapenem Antibiotics for the Empiric Treatment of Nosocomial Pneumonia: A Systematic Review and Meta-analysis

Previous meta-analyses suggested that treating hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), with empiric carbapenems was associated with lower mortality rates but higher rates of clinical failure for pseudomonal pneumonia. This study was an updated meta-analysis with sensitivity analyses and meta-regression to better understand the impact of carbapenem use in HAP/VAP. What is the efficacy of carbapenems for empiric treatment of nosocomial pneumonia? Databases were searched for randomized controlled studies evaluating empiric treatment for HAP and/or VAP, and studies were included comparing carbapenem- vsnon-carbapenem-containing regimens. The primary outcome was all-cause mortality. Secondary outcomes included subgroup stratification and resistance development. Of 9,140 references, 20 trials enrolling 5,489 patients met inclusion criteria. For mortality, carbapenem use had a risk ratio (RR) of 0.84 (95%CI, 0.74-0.96; P= .01). Stratified according to VAP proportion (< 33%, 33%-66%, and > 66%), RRs were 0.95 (95%CI, 0.77-1.17; P= .66), 0.78 (95%CI, 0.57-1.07; P= .13), and 0.81 (95%CI, 0.65-0.99; P= .04), respectively. Stratified according to severity, only groups with Acute Physiology and Chronic Health Evaluation II scores< 14 and between 14 and 17 showed mortality benefit (RRs of 0.64 [95%CI, 0.45-0.92; P= .01] and 0.77 [95%CI, 0.61-0.97; P= .03]). Meta-regression did not show an association between Pseudomonas prevalence and mortality (P= .44). Carbapenem use showed a trend toward developing resistance (RR, 1.40; 95%CI, 0.95-2.06; P= .09) and a 96%probability of resistance emergence. Carbapenem-based empiric regimens were associated with lower mortality rates compared with non-carbapenems, largely driven by trials of VAP. The mortality effect was not observed in trials with high disease severity and was not associated with Pseudomonas. The mortality difference was observed mainly in studies that used ceftazidime as control. There was a trend toward increasing resistance associated with carbapenems. International Prospective Register of Systematic Reviews; No. CRD42018093602; URL: https://www.crd.york.ac.uk/prospero/.

Implementation of French Recommendations for the Prevention and the Treatment of Hospital-acquired Pneumonia: A Cluster-randomized Trial.

We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38-56%) in the intervention group and 42% (IQR, 25-53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5-14 days) in the control group and 9 days (IQR, 5-20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69-2.01; P = .10). The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. NCT03348579.

Clinical Benefits of Piperacillin/Tazobactam versus a Combination of Ceftriaxone and Clindamycin in the Treatment of Early, Non-Ventilator, Hospital-Acquired Pneumonia in a Community-Based Hospital.

PurposeThere is an increasing prevalence of multidrug-resistant (MDR) organisms worldwide. Therefore, broad-spectrum antibiotics are recommended in the treatment of hospital-acquired pneumonia (HAP). However, it remains controversial whether patients with early onset, non-ventilator HAP (NV-HAP) should also be empirically treated with broad-spectrum antibiotics. We compared the clinical benefit of ceftriaxone plus clindamycin vs piperacillin/tazobactam as the initial empirical treatment of adults with early NV-HAP.Patients and MethodsRetrospective cohort study was conducted in adult patients who were diagnosed with early, NV-HAP between January 2013 and June 2017 at a community-based tertiary care hospital. Patients were eligible for inclusion if they had received empiric treatment with either ceftriaxone and clindamycin or piperacillin/tazobactam for at least 3 days. Patients with increased risk of MDR pathogens were excluded.ResultsA total of 89 patients were treated with ceftriaxone and clindamycin, while 124 received piperacillin/tazobactam. There were no significant differences between the two antibiotic groups with regard to median age, sex, or risk of pneumonia. The 30-day all-cause mortality did not differ significantly between the ceftriaxone plus clindamycin and piperacillin/tazobactam groups (4.5% vs 1.6%, P=0.202, respectively). However, in multivariate analysis, clinical failure was more frequent in the ceftriaxone plus clindamycin group than in the piperacillin/tazobactam group (HR 3.316; 95% CI, 1.589–6918, P=0.001).ConclusionTreatment with piperacillin/tazobactam was more effective than that with ceftriaxone plus clindamycin in patients with early NV-HAP. This study supports the recent treatment recommendations that patients with early NV-HAP should be treated empirically with broad-spectrum antibiotics.

Outcomes and prognostic factors of tigecycline treatment for hospital-acquired pneumonia involving multidrug-resistant Acinetobacter baumannii.

Objective: To compare outcomes and prognostic factors of tigecycline (TC)-based treatment with those of other antibiotic-based treatments in the treatment of hospital-acquired pneumonia caused by multidrug-resistant Acinetobacter baumannii (MDRAB).Methods: A retrospective analysis of data was performed from all patients ≥18 years who were treated in the ICU at Xiangya Hospital, Changsha, China (January 2016 to June 2017) with hospital-acquired pneumonia involving monomicrobial MDRAB. Patients were separated into TC and non-TC groups.Results: Of 86 MDRAB-positive patients, 59 were in the TC group and 27 were in the non-TC group. The 28-day death rates were not significantly different between the two groups, but the TC group had significantly more patients with a good clinical prognosis than the non-TC group. Although prognostic markers for a poor clinical response were sepsis, procalcitonin concentration and APACHE II scores, TC therapy was found to be a protective factor.Conclusions: TC based therapy was associated with a positive clinical response in the treatment of MDRAB caused hospital-acquired pneumonia. Further studies are required to confirm our results.

Treatment of hospital-acquired pneumonia with multi-drug resistant organism by Buzhong Yiqi decoction based on Fuzheng Quxie classical prescription: study protocol for a randomized controlled trial

BackgroundDrug resistance in China is becoming a more and more serious issue. Infection by drug-resistant bacteria has become a major disease that seriously threatens the health of Chinese people and affects national medical finance. Therefore, it is of great scientific and clinical significance to actively carry out research on the prevention and treatment of infections by multi-drug resistant organisms (MDRO). Previous studies by the authors suggested that patients with hospital-acquired pneumonia caused by MDRO mostly showed the pathological state of “insufficient healthy Qi and internal accumulation of pathogenic Qi” and “acute deficiency syndrome” mainly characterized by Qi deficiency. Buzhong Yiqi decoction is a famous classic prescription in traditional Chinese medicine (TCM) for treating internal damage fever. This study intends to provide an evidence-based rationale for Buzhong Yiqi decoction in treating MDRO hospital-acquired pneumonia by conducting a multi-center randomized controlled clinical study.Methods/designThis study is designed to be a multi-center randomized controlled study in which patients are assigned randomly into control (standard therapy) and trial (standard therapy plus Buzhong Yiqi decoction) groups. The patients will be selected from the emergency department and the ICU inpatient department of five study sites and will all be diagnosed with MDRO hospital-acquired pneumonia and meet the inclusion criteria. Forty patients are to be enrolled in each study site, resulting in a total of 200 patients in the study. The treatment course is 28 days.DiscussionIn this study: (1) the theory of “acute Qi deficiency” in MDRO hospital-acquired pneumonia is put forward for the first time, and the basic theories of TCM are further improved; (2) a multi-center randomized controlled clinical study will be performed for the first time with Buzhong Yiqi decoction, the classic prescription for reinforcing healthy Qi and eliminating pathogenic Qi, providing a reliable evidence-based rationale for the treatment of MDRO pulmonary infection with TCM; (3) the clinical application and modern disease spectrum of Buzhong Yiqi decoction is expanded, and the scientific notion of “treating different diseases with the same method” is enriched further.Trial registrationChina Clinical Trial Registry, ChiCTR1900022429. Registered on April 11, 2019. http://www.chictr.org.cn/listbycreater.aspx.

PIN76 BUDGET IMPACT OF CEFTAZIDIME AVIBACTAM (CAZ-AVI) FOR COMPLICATED INTRA-ABDOMINAL INFECTION, COMPLICATED URINARY TRACT INFECTION AND HOSPITAL-ACQUIRED PNEUMONIA IN SINGAPORE

Antimicrobial resistance is a major public health threat in Singapore. Access to quality medicine is critical to address risk of antimicrobial resistance. CAZ-AVI was developed for treatment of a broad range of gram-negative bacterial infections. This study aimed to find budget impact from the perspective of Singapore healthcare with CAZ-AVI and currently available antibiotics in the treatment of complicated intra-abdominal (cIAI), complicated urinary tract (cUTI), hospital-acquired pneumonia (HAP) and aerobic Gram-negative infections with limited treatment options (Infections w/ LTO) A budget Impact Model was developed with 3-year-time horizon. Cost data were from Singapore statistics, public surveillance and literature reviews. Costs were estimated based on prevalence of diseases, type of medication, period of treatment, length of hospital stay, rate of adverse event, market competition and monitoring costs. Based on the assumption of CAZ-AVI introduction, overall budget was calculated by estimating costs of treatment options of cIAI, cUTI, HAP and Infections with LTO reflecting proportion of patients for 3 years comparing with current available options. Total eligible population for 3 years was estimated around 22,000 and 3-year-total costs including CAZ-AVI were around 340 million SGD. When CAZ-AVI included as a new treatment, 1.5% or 240 SGD per patient was increased for 3 years. Due to drug cost of CAZ-AVI, treatment costs of 6 million SGD (17%) were increased. Hospital stay were decreased from around 349,000 days with current available options to around 348,000 days when CAZ-AVI was included. Impact of CAZ-AVI inclusion for 3 years by cIAI, cUTI, HAP and Infections with LTO are 138 SGD (1%), 115 SGD (1%), 205 SGD (1%), 827 SGD (3.5%), respectively. Impact on new options of CAZ-AVI in the treatment of cIAI, cUTI, HAP and infections with LTO can be marginal on the total Singapore healthcare budget.

2190. Influence of Microbiological Culture Results on Antibiotic Choice for Veterans with Hospital-Acquired Pneumonia

BackgroundRespiratory specimens help inform the treatment of hospital-acquired pneumonia (HAP), permitting clinicians to ensure effective and, ideally, narrow-spectrum antibiotic therapy. Here, we examine changes in antibiotic regimens to treat HAP based on the antibiotic susceptibility of pathogens recovered from respiratory samples.MethodsAt a single Veterans Affairs (VA) Medical Center, we identified veterans hospitalized between October 2014 and September 2018 with HAP, defined as a clinical respiratory sample obtained >48 hours after admission and corresponding clinical signs and symptoms. Exclusion criteria were death, transfer to hospice care or discharge within 48 hours of sample collection or admission from an outside hospital. For each specimen, we assessed timestamps for collection, Gram stain, identification of organisms and results of susceptibility testing. We used the antibiotic spectrum index (ASI) to assess changes in antibiotics given to patients during hospitalization and at discharge.ResultsBetween October 2014 and September 2018, 70 veterans met our inclusion criteria and experienced 73 episodes of HAP. Their mean age was 66.2 years (±9 years) and 47 (67%) had chronic pulmonary disease. All-cause mortality at 30-days after specimen collection was 14%. The median time from specimen collection to Gram stain result was 0.8 days (interquartile range (IQR) 0.1–1.9) and to antibiotic susceptibility results was 2.4 days (IQR 1.5–3.3). The most common bacteria recovered were Enterobacteriaceae (20 isolates), Pseudomonas aeruginosa (11 isolates), Streptococcus spp. and Staphylococcus aureus (8 isolates each); colonization with Candida spp. was frequent (26 isolates). Vancomycin and piperacillin–tazobactam were the most common antibiotics on day 0 (24%, 22%, respectively) and day 3 (21%, 13%, respectively). Compared with the day of sample collection (day 0), the ASI score was lower at day 3 in 23 (32%) and higher in 21 (29%) cases.ConclusionThe high proportion of escalation and de-escalation of antibiotics suggests that results of bacteria identification and susceptibility testing influence therapeutic decisions, emphasizing the importance of obtaining respiratory samples to inform treatment of HAP and improve antibiotic stewardship.Disclosures All authors: No reported disclosures.

Chinese guidelines for the diagnosis and treatment of hospital-acquired pneumonia and ventilator-associated pneumonia in adults (2018 Edition).

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common hospital-acquired infections in China. The difficulty in diagnosis and treatment of HAP/VAP leads to high mortality. In China, it has been nearly two decades since the initial “ Guideline for the Diagnosis and Treatment of Hospital-acquired Pneumonia ( draft )” was published in 1999 (1). Afterwards, a number of guidelines for HAP/VAP have been published or updated at home and abroad (2-10). The definitions of HAP/VAP have been changing as more and more relevant researches available highlighting greater details. Moreover, there are growing evidence in the epidemiology, etiology, clinical diagnosis and treatment of HAP/VAP, especially the accumulating evidence from the researches in China, which shows that the distribution and antibiotic resistance rate of HAP/VAP pathogens in China are largely different from the data reported in other countries. Therefore, it is necessary to amend the initial guideline in 1999 accordingly in order to better guide clinical practice.

Clinical experience with tigecycline in the treatment of hospital-acquired pneumonia caused by multidrug resistant Acinetobacter baumannii

BackgroundTigecycline, with broad in vitro antibacterial activity, has been widely used off-label for nosocomial pneumonia caused by multi-drug resistant Acinetobacter baumannii (MDRAB). However, many concerns have been raised about the efficacy of tigecycline treatment as the inconsistent results from previous clinical studies.MethodsThis retrospective study evaluated the outcome of adult patients with monomicrobial MDRAB nosocomial pneumonia treated with tigecycline between 2015 and 2017. Results.A total of 77 patients was eligible for this study, and the overall clinical success and 30-day survival rates were 70.03 and 70.13%, respectively, however, the microbiological eradication rate was relatively low (48%). Multivariate analysis indicated that shorter duration of tigecycline use associated with increased clinical failure, whereas higher CURB65 scores, mechanical ventilation and tigecycline resistant to MDRAB have significant association with 30-day mortality.ConclusionsOur results suggest that tigecycline is one of the potential choices for the treatment of hospital-acquired pneumonia caused by MDRAB, especially with a MIC≤2 mg/L. In addition, a longer duration of tigecycline treatment may be required to insure better clinical outcomes.

Inhalation with intravenous loading dose of colistin in critically ill patients with pneumonia caused by carbapenem-resistant gram-negative bacteria.

Background:Despite the increasing use of colistin in clinical practice, the optimal dosing, and administration route have not been established. This study aimed to evaluate the clinical outcome and safety of intravenous (IV) colistin with a loading dose (LD) and adjunctive aerosolized (AS) colistin administration in critically ill patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) caused by carbapenem-resistant gram-negative bacteria (CRGNB).Methods:We retrospectively reviewed 191 critically ill patients who received colistin for the treatment of HAP or VAP caused by CRGNB. Patients were divided into three groups: non-LD IV (patients received only IV colistin without LD), LD IV (patients received only IV colistin with LD), and AS–LD (patients received IV colistin with LD and adjunctive AS colistin).Results:There was no difference in clinical response between the three groups. However, the rate of microbiological eradication was significantly higher in the AS–LD group (60%) than in the non-LD IV (31%), and LD IV (33%) groups (p = 0.010). Patients treated with adjunctive AS colistin in combination with LD IV had significantly lower 30-day mortality rates than patients treated with IV colistin alone (p = 0.027). After adjusting for potential confounding factors, adjunctive AS colistin was still significantly associated with lower mortality (adjusted OR 0.338, CI 95% 0.132–0.864, p = 0.024). However, nephrotoxicity did not change according to the use of LD regimen and AS colistin administration (p = 0.100).Conclusions:Adjunctive AS colistin in combination with IV colistin with LD was related to an improved 30-day mortality and microbiological outcome without an increase in nephrotoxicity in critically ill patients with HAP and VAP caused by CRGNB. The reviews of this paper are available via the supplemental material section.

Brief summary of French guidelines for the prevention, diagnosis and treatment of hospital-acquired pneumonia in ICU

BackgroundThe French Society of Anaesthesia and Intensive Care Medicine and the French Society of Intensive Care edited guidelines focused on hospital-acquired pneumonia (HAP) in intensive care unit. The goal of 16 French-speaking experts was to produce a framework enabling an easier decision-making process for intensivists.ResultsThe guidelines were related to 3 specific areas related to HAP (prevention, diagnosis and treatment) in 4 identified patient populations (COPD, neutropenia, post-operative and paediatric). The literature analysis and the formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research over the last 10 years was conducted based on publications indexed in PubMed™ and Cochrane™ databases.ConclusionsHAP should be prevented by a standardised multimodal approach and the use of selective digestive decontamination in units where multidrug-resistant bacteria prevalence was below 20%. Diagnosis relies on clinical assessment and microbiological findings. Monotherapy, in the absence of risk factors for multidrug-resistant bacteria, non-fermenting Gram-negative bacilli and/or increased mortality (septic shock, organ failure), is strongly recommended. After microbiological documentation, it is recommended to reduce the spectrum and to prefer monotherapy for the antibiotic therapy of HAP, including for non-fermenting Gram-negative bacilli.

Comparison of Piperacillin/Tazobactam Dosing (13.5 g/day vs. 18 g/day) for the Treatment of Hospital-Acquired Pneumonia and Ventilator-associated Pneumonia in Intensive Care Unit

Comparison of Piperacillin/Tazobactam Dosing (13.5 g/day <i>vs.</i> 18 g/day) for the Treatment of Hospital-Acquired Pneumonia and Ventilator-associated Pneumonia in Intensive Care Unit

Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections.

Ceftazidime-avibactam (Zavicefta®) is an intravenously administered combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam. In the EU, ceftazidime-avibactam is approved for the treatment of adults with complicated urinary tract infections (cUTIs) [including pyelonephritis], complicated intra-abdominal infections (cIAIs), hospital-acquired pneumonia (HAP) [including ventilator-associated pneumonia (VAP)], and other infections caused by aerobic Gram-negative organisms in patients with limited treatment options. This article discusses the in vitro activity and pharmacological properties of ceftazidime-avibactam, and reviews data on the agent's clinical efficacy and tolerability relating to use in these indications, with a focus on the EU label. Ceftazidime-avibactam has excellent in vitro activity against many important Gram-negative pathogens, including many extended-spectrum β-lactamase-, AmpC-, Klebsiella pneumoniae carbapenemase- and OXA-48-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa isolates; it is not active against metallo-β-lactamase-producing strains. The clinical efficacy of ceftazidime-avibactam in the treatment of cUTI, cIAI and HAP (including VAP) in adults was demonstrated in pivotal phaseIII non-inferiority trials with carbapenem comparators. Ceftazidime-avibactam treatment was associated with high response rates at the test-of-cure visit in patients with infections caused by ceftazidime-susceptible and -nonsusceptible Gram-negative pathogens. Ceftazidime-avibactam was generally well tolerated, with a safety and tolerability profile consistent with that of ceftazidime alone and that was generally typical of the injectable cephalosporins. Thus, ceftazidime-avibactam represents a valuable new treatment option for these serious and difficult-to-treat infections.

The Role of Aerolized Colistin in the Treatment of Hospital-Acquired Pneumonia: Experience of Multicenter From Turkey: Erratum.

Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Efficacy and safety of tigecycline monotherapy versus combination therapy for the treatment of hospital-acquired pneumonia (HAP): a meta-analysis of cohort studies

The broad spectrum antibiotic tigecycline shows promising efficacy against many multiple drug resistant (MDR) pathogens. However, its clinical efficacy in the treatment of hospital-acquired pneumonia (HAP) is unclear. Several studies have reported on the treatment failures of tigecycline monotherapy, suggesting that it may not be sufficient to control severe infections. Combination therapy has become an option to treat MDR bacterial infections. We conducted a literature search using PubMed, Cochrane Library, Embase, Elsevier and the Web of Knowledge databases up to 29 February 2017 to identify relevant published studies. Studies were considered eligible if they were a cohort study that assessed mortality and the safety of tigecycline monotherapy versus combination therapy with other antimicrobial agents for HAP. The primary outcome was treatment mortality rate, while the secondary outcomes were adverse events. Meta-analysis was done using fixed-effects models. Five trials were included. The monotherapy tigecycline had a higher mortality compared to the combination therapy group. There was a significant difference for the treatment of HAP. However, two prospective cohort studies showed that there was no significant difference in mortality rate between the tigecycline monotherapy and the tigecycline combination therapy. Three retrospective cohort studies showed that tigecycline monotherapy had a high mortality rate. Tigecycline combination therapy efficiently treats HAP. There is a great need for well-designed studies to evaluate the effectiveness and safety of combination therapies as they compare to tigecycline monotherapy.

국내 병원획득 폐렴 원인균의 경험적 항균제에 대한 내성 현황

Background : Although the prevalence of antibiotic resistance may vary according to region, there is no guidance developed in Korea on the use of empirical antibiotics for the treatment of hospitalacquired pneumonia (HAP). The purpose of this study was to investigate the patterns of empiric antibiotic therapy and resistance of the isolated pathogens to the empirical antibiotics in the management of HAP in Korea. Methods : A retrospective analysis was conducted using the electronic medical records of the HAP patients January 2014-December 2015 in Korea. The patterns of prescribing empirical antibiotics and resistance of the isolated pathogens to the empirical antibiotics were examined. Results : A total of 170 patients was analyzed. Piperacillin/tazobactam was the key agent in the empirical antibiotics. The most common pathogen was Staphylococcus aureus (27.9%) followed by Acinetobacter baumannii (21.6%), Klebsiella pneumoniae (11.1%), Pseudomonas aeruginosa (6.3%), Stenotrophomonas maltophilia (5.8%), Enterobacter aerogenes (5.3%), and Escherichia coli (5.3%). The resistance rates of S. aureus to ciprofloxacin was 76%. E. coli had high level of resistance rate to ciprofloxacin (80%) and low resistance rate to imipenem (10%). K. pneumoniae and P. aeruginosa showed very high level of sensitivity to imipenem (100%) and cefepime (91.7%), respectively. To piperacillin/tazobactam, E. coli, E. erogenes, K. pneumoniae, and P. aeruginosa showed high level of sensitivity (52.4-100%). A. baumannii exhibited high-level resistance rates (63.4-85.4%) to the empirical antibiotics, including cefepime, ceftazidime, ciprofloxacin, imipenem, and piperacillin/tazobactam. Conclusion : The empirical antibiotic therapy was appropriate for the initial treatment of HAP owing to the adequate antibiotic coverage. Piperacillin/tazobactam was used in most patients and the most common pathogens including Pseudomonas aeruginosa had high level of sensitivity to the drug. The high level of resistance of A. baumannii to the empirical antibiotics is one of the major challenges in treating HAP.

Сучасні принципи діагностики та лікування пневмонії, асоційованої з медичним доглядом, лікарняної і вентилятор-асоційованої пневмоній у дітей: Review Up To Date 2017

Hospital-acquired and ventilator-associated pneumonia are common causes of morbidity and mortality in children of different age groups, despite improved modern respiratory care, a wide range of antibiotic therapy, and the possibility of disease prevention. Pneumonia associated with medical care has a course similar to the hospital-acquired pneumonia and includes the episode of pneumonia in patients who were hospitalized for >2 days during the last 90 days; or live in health care facilities and need permanent care; received intravenous and / or chemotherapy for the last 30 days; visited the hemodialysis department.The purpose of this publication is to reduce the complications and mortality rate of children with pneumonia associated with medical care, hospital-acquired and ventilator-associated pneumonia by familiarizing pediatric pulmonologists, intensive care physicians, surgeons with current diagnostic and treatment recommendations. We have attempted to explore and analyze the data available from current sources on the principles of treatment for pneumonia associated with medical care, hospital-acquired and ventilator-associated pneumonia, and to synthesize current concepts for childhood patients. The article is based on the evidence base, strength and degree of evidence defined in each recommendation on patient management. Modern diagnostics of hospital-acquired pneumonia takes into account the timing of onset of the disease. In children with the late-onset of hospital-acquired pneumonia there is a high frequency of multidrug-resistant flora, therefore, more frequent combination therapy is chosen. Children with the early onset of hospital-acquired pneumonia are prescribed monotherapy of antibiotics. Most of the antibiotic therapy principles, which applied to the treatment of hospital-acquired pneumonia, can be also applied to the management of pneumonia associated with medical care. The etiology of ventilator-associated pneumonia is associated with aspiration of pathogens from the oropharynx and from the sites around the endotracheal cuff, determines the advantage of non-invasive ventilation techniques over mechanical ones. The review provides a detailed algorithm for the diagnosis of pneumonia associated with medical care, hospital-acquired and ventilator-associated pneumonia, as well as a differentiated approach to the antibiotic treatment of the patient.

Clinical practice guidelines of HAP/VAP in 2016: the updates

Hospital acquired pneumonia (HAP) and ventilatorassociated pneumonia (VAP) are common hospital-acquired infections with higher mortality, longer hospital stay and more hospitalization expenses. With the latest research results and evidence-based guideline methodology, Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) have collaborated to create updated guidelines for the diagnosis and treatment of HAP and VAP in 2016. It is worth critically reading and thinking that most recommendations are supported by low-quality or very-low quality evidence and some strong recommendations is different from the actual clinical work in China. We will focus on these topics that are associated closely with clinical practice and inconsistent with the current implementation in China to provide better understanding of the guideline.