Severe Hospital-acquired Pneumonia Research Articles

Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model.

Pseudomonas aeruginosa, a leading cause of severe hospital-acquired pneumonia, causes infections with up to 50% mortality rates in mechanically ventilated patients. Despite some knowledge of virulence factors involved, it remains unclear how P. aeruginosa disseminates on mucosal surfaces and invades the tissue barrier. Using infection of human respiratory epithelium organoids, here we observed that P. aeruginosa colonization of apical surfaces is promoted by cyclic di-GMP-dependent asymmetric division. Infection with mutant strains revealed that Type 6 Secretion System activities promote preferential invasion of goblet cells. Type 3 Secretion System activity by intracellular bacteria induced goblet cell death and expulsion, leading to epithelial rupture which increased bacterial translocation and dissemination to the basolateral epithelium. These findings show that under physiological conditions, P. aeruginosa uses coordinated activity of a specific combination of virulence factors and behaviours to invade goblet cells and breach the epithelial barrier from within, revealing mechanistic insight into lung infection dynamics.

Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

Protocol of a multicenter, single-blind, randomized, parallel controlled trial evaluating the effect of microbiological rapid on-site evaluation (M-ROSE) guiding anti-infection treatment in patients with severe hospital-acquired pneumonia

IntroductionThe mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation (M-ROSE) might be a useful technique to identify the pathogens in the early stage; however, the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear.Methods/designThis is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the ICU outcome (mortality). The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP and may change the prevalence of multi-drug resistant bacteria.Ethics and disseminationThis trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001).Trial registrationClinicalTrials.gov NCT05300776. Registered on 25 March 2022.

Pathogen Diagnosis Value of Nanopore Sequencing in Severe Hospital-Acquired Pneumonia Patients.

Next-generation sequencing of the metagenome (mNGS) is increasingly used in pathogen diagnosis for infectious diseases due to its short detection time. The time for Oxford Nanopore Technologies (ONT) sequencing-based etiology detection is further shortened compared with that of mNGS, but only a few studies have verified the time advantage and accuracy of ONT sequencing for etiology diagnosis. In 2022, a study confirmed that there was no significant difference in sensitivity and specificity between ONT and mNGS in suspected community-acquired pneumonia patients, which there was no clinical study verified in patients with SHAP. From October 24 to November 20, 2022, 10 patients with severe hospital-acquired pneumonia (SHAP) in the Nanfang Hospital intensive care unit (ICU) were prospectively enrolled. Bronchoalveolar lavage fluid (BALF) was collected for ONT sequencing, mNGS, and traditional culture. The differences in pathogen detection time and diagnostic agreement among ONT sequencing, mNGS, traditional culture method, and clinical composite diagnosis were compared. Compared with mNGS and the traditional culture method, ONT sequencing had a significant advantage in pathogen detection time (9.6±0.7 h versus 24.7±2.7 h versus 132±58 h, P <0.05). The agreement rate between ONT sequencing and the clinical composite diagnosis was 73.3% (kappa value=0.737, P <0.05). ONT sequencing has a potential advantage for rapidly identifying pathogens.

Epidemiology and Characteristics of Respiratory Syncytial Virus Pneumonia in Critically Ill Adults.

Severe respiratory syncytial virus (RSV)-associated pneumonia in adults has rarely been addressed. We investigated the burden and clinical characteristics of severe RSV-associated pneumonia in critically ill adult patients. We analyzed a prospective cohort of 2865 adults with severe pneumonia who were admitted to the intensive care unit in a 2700-bed tertiary care hospital from 2010 to 2019. The epidemiology, characteristics, and outcomes of 92 cases of severe RSV-associated pneumonia and 163 cases of severe influenza virus (IFV)-associated pneumonia were compared. Of 1589 cases of severe community-acquired pneumonia, the incidence of RSV-associated pneumonia was less than half that of IFV-associated pneumonia (3.4% vs 8.1%). However, among 1276 cases of severe hospital-acquired pneumonia (HAP), there were slightly more cases of RSV-associated than IFV-associated pneumonia (3.8% vs 3.5%). During the 9 epidemic seasons, RSV-A (5 seasons) and RSV-B (4 seasons) predominated alternately. Structural lung disease, diabetes mellitus, and malignancy were common underlying diseases in both groups. Immunocompromise (57.6% vs 34.4%; P < .001) and hospital acquisition (47.8% vs 23.9%; P < .001) were significantly more common in the RSV group. Coinfection with Streptococcus pneumoniae (3.3% vs 9.8%; P = .08) and methicillin-susceptible Staphylococcus aureus (1.1% vs 6.8%; P = .06) tended to be less frequent in the RSV group. The 90-day mortality was high in both groups (39.1% vs 40.5%; P = .89). RSV infection was associated with substantial morbidity and mortality in critically ill adult patients, similar to IFV. The relatively higher incidence of RSV in severe HAP suggests that the transmissibility of RSV can exceed that of IFV in a hospital setting.

1224. The incidence of severe C. striatum hospital-acquired pneumonia sharply increased and was associated with a high mortality rate

Abstract Background The clinical information on patients with severe C. striatum pneumonia who require intensive care unit admission is currently limited. Methods We investigated the incidence and characteristics of severe Corynebacterium striatum pneumonia during a 6-year period at Asan Medical Center in comparison with severe pneumonia associated with MRSA. Results Between 2014 and 2019, there were 27 adult cases of severe C. striatum pneumonia. The majority of the cases (70.4%) were hospital-acquired pneumonia (HAP), and about half of the patients (51.9%) were immunocompromised. The incidence of C. striatum HAP significantly increased from 1.0% (2/200) in 2014-2015 to 5.4% (10/185) in 2018-2019 (P &amp;lt; 0.001), while the incidence of severe methicillin-resistant Staphylococcus aureus (MRSA) HAP significantly decreased from 12.0% to 2.7% during the same period. Of the 75 HAP cases whose bacterial pathogens were identified in 2018–2019, C. striatum was responsible for 13.3% of the cases. The 90-day mortality rates were similarly high in the C. striatum and MRSA groups (59.3% vs. 50.5%, P = 0.42). Conclusion In conclusion, C. striatum was a major pathogen of recent severe HAP and was associated with a substantially high mortality rate. Disclosures All Authors: No reported disclosures.

Severe Pneumonia Caused by Corynebacterium striatum in Adults, Seoul, South Korea, 2014-2019.

We investigated the proportion and characteristics of severe Corynebacterium striatum pneumonia in South Korea during 2014-2019. As part of an ongoing observational study of severe pneumonia among adult patients, we identified 27 severe C. striatum pneumonia cases. Most (70.4%) cases were hospital-acquired, and 51.9% of patients were immunocompromised. C. striatum cases among patients with severe hospital-acquired pneumonia (HAP) increased from 1.0% (2/200) during 2014-2015 to 5.4% (10/185) during 2018-2019, but methicillin-resistant Staphylococcus aureus (MRSA) infections among severe HAP cases decreased from 12.0% to 2.7% during the same timeframe. During 2018-2019, C. striatum was responsible for 13.3% of severe HAP cases from which bacterial pathogens were identified. The 90-day mortality rates were similarly high in the C. striatum and MRSA groups. C. striatum was a major cause of severe HAP and had high mortality rates. This pathogen is emerging as a possible cause for severe pneumonia, especially among immunocompromised patients.

Sulbactam combined with tigecycline improves outcomes in patients with severe multidrug-resistant Acinetobacter baumannii pneumonia

BackgroundThe purpose of this study was to review the treatment plan of patients with multidrug-resistant Acinetobacter baumannii (MDR-AB) pneumonia and analyze the factors associated with patient deaths and the medication regimen.MethodsWe collected 1,823 qualified respiratory specimens that were culture-positive for MDR-AB. 166 patients confirmed to have hospital-acquired MDR-AB pneumonia were selected as the research subjects. The differing clinical characteristics and treatment interventions between the surviving group and death group within 28 days were analyzed.ResultsThe mortality rate was high for those aged > 75 years (p = 0.001). Patients who underwent invasive catheter placement (p < 0.001) and mechanical ventilation (p = 0.046) had a higher mortality rate. Combination therapy with tigecycline can reduce the mortality rate (p < 0.001) of MDR-AB pneumonia in patients with carbapenem-resistant AB(CRAB). Combination therapy with sulbactam was shown to reduce the mortality rate (p < 0.001), and high-dose sulbactam (> 3 g/day) might be better than low-dose sulbactam (≤ 3 g/day).ConclusionReducing the time of invasive catheter placement and mechanical ventilation in patients in the intensive care unit (ICU), antimicrobial treatment, combined with tigecycline and sulbactam, might help reduce the mortality rate in patients with severe MDR-AB hospital-acquired pneumonia.

Investigation of Microbial Etiology in Endotracheal Aspirate Samples of Severe Pneumonia Patients by Multiplex PCR and Culture Method

Objectives: The probability of detecting viral and atypical agents in pneumonia patients has increased with the molecular methods used in recent years. We aimed to investigate pneumonia pathogens in endotracheal aspiration samples (ETA) of patients with severe community-acquired (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) by multiplex polymerase chain reaction (m-PCR) and culture method. Methods: A prospective study was performed between December 2019 and October 2020. Patients 18 years and older with pneumonia followed in ICU on the mechanical ventilator were included. COVID-19 patients were excluded. Patients were grouped as CAP, HAP, and VAP. Two ETA samples were obtained from patients within 48 hours of the pneumonia diagnosis. Respiratory pathogens were investigated in samples by viral-bacterial m-PCR and bacterial culture methods. Results: 74 patients were included in the study. m-PCR of ETA samples achieved pathogen detection in 87.8% of patients compared with 58.1% with culture methods. The most common pathogen detected by m-PCR was Streptococcus pneumoniae in both CAP and HAP patients and Klebsiella spp. in VAP patients. The most common pathogen isolated by culture was Staphylococcus aureus in both CAP and HAP patients and Klebsiella spp. in VAP patients. Atypical pneumonia pathogens were positive for 14.9% of the patients. Atypical pathogens were recovered from 28.5% of CAP patients and 23.1% of HAP patients. Viruses constituted all of the atypical pathogens recovered from HAP patients. No atypical pathogen was found in VAP patients. Conclusion: In this study, S. pneumoniae was the most common pathogen detected with m-PCR, and S. aureus and Klebsiella spp. were the most common pathogens detected with culture. Determination of microbial etiology of lower respiratory tract samples by molecular methods for diagnosing severe CAP and HAP may be beneficial in terms of treatment. Keywords: pneumonia, multiplex PCR, endotracheal aspirate, conventional methods

Clinical Value of Metagenomics Next-Generation Sequencing in Bronchoalveolar Lavage Fluid for Patients with Severe Hospital-Acquired Pneumonia: A Nested Case-Control Study.

BackgroundMetagenomics next-generation sequencing (mNGS) is more efficient in identifying pathogens responsible for pneumonia. However, whether these patients ultimately benefit from this improvement remains unknown.MethodsIn this retrospective, nested, case–control study, patients with severe hospital-acquired pneumonia (HAP) who had undergone mNGS of bronchoalveolar lavage fluid while in our intensive care unit from March 2017 to December 2020 (n = 33) were matched in a ratio of 1 to 2 (n = 66) by sex, age, comorbidities, immune status, Acute Physiology and Chronic Health Evaluation II score, severity of pulmonary infection, and use of extracorporeal life support with patients who had undergone conventional microbiological testing only. The primary outcome was 90-day mortality; secondary outcomes being length of intensive care unit stay, duration of mechanical ventilation support, 7-day and 28-day mortality, and efficacy of treatment of pulmonary infection.ResultsIn the CMT group, 17 patients (25.8%) had negative results, whereas only one (3.0%) had negative results in the mNGS group (P < 0.001). After receipt of microbiology results, antibiotics were altered in 23/33 patients (70.0%) in the mNGS group, but in only 29/66 (43.9%) in the CMT group (P = 0.016). Pulmonary infection-related findings improved in 20/33 patients (60.6%) in the mNGS group in the subsequent 7 days, but in only 25/66 (37.9%) in the CMT group (P = 0.032). However, the 28-day (33.3% vs 31.2%, P = 1.0) and 90-day (48.5% vs 45.5%, P = 0.78) mortality rates did not differ significantly between the two groups. These findings were supported by Cox-regression and Kaplan–Meier survival curve analyses.ConclusionmNGS is helpful in the treatment of severe HAP but does not improve medium or long-term survival rates, especially in patients with severe comorbidities.

Clinical effectiveness of cefoperazone-sulbactam vs. piperacillin-tazobactam for the treatment of pneumonia in elderly patients

Both cefoperazone-sulbactam (CFP-SUL) and piperacillin-tazobactam (PIP-TAZ) are β-lactam/β-lactamase inhibitor antibiotics and have a similar antimicrobial spectrum. However, comparative clinical efficacy and safety of CFP-SUL and PIP-TAZ for the treatment of pneumonia remain largely unknown, especially in elderly patients. Based on a multi-centre registry database, patients aged ≥65 years, diagnosed with severe community-acquired pneumonia (SCAP), hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), and given empirical therapy with CFP-SUL or PIP-TAZ were included in the analysis. The primary outcome of interest was the proportion of patients achieving clinical cure. Multi-variate logistic regression was conducted to compare odds ratios (OR) for the outcome between patients who received CFP-SUL and patients who received PIP-TAZ. In total, 941 elderly patients (624 with SCAP, and 317 with either HAP or VAP) were included in this study. Overall in-hospital mortality for the entire cohort was 19%. Clinical cure was achieved in 81% and 83% of patients with SCAP and HAP/VAP, respectively. Multi-variate logistic regression analysis showed similar odds for clinical cure for patients receiving CFP-SUL or PIP-TAZ among those with SCAP [adjusted OR 1.10, 95% confidence interval (CI) 0.71-1.70] or HAP/VAP (adjusted OR 0.72, 95% CI 0.30-1.76). Regarding safety, both CFP-SUL and PIP-TAZ were generally well tolerated with few reported adverse events. Among elderly patients with SCAP or HAP/VAP, empirical therapy with CFP-SUL is a viable alternative to PIP-TAZ, while considering antibiotic heterogeneity in the antimicrobial stewardship context.

Severe Pneumonia: Etiology and Outcome in a Tertiary Hospital in Indonesia

Background: Severe pneumonia represents a subset of life-threatening pneumonia. The mortality rate ofpatients with severe pneumonia is considerably high. This study aims to determine the etiology and outcomeof severe pneumonia.Methods: An observational prospective study was conducted from September 2017 to September 2018 onpneumonia patients in a tertiary hospital. Clinical and diagnostic evaluations were carried out to assess theseverity of the disease, etiology, comorbidities, and several other factors associated with outcomes.Results: 140 pneumonia patients were evaluated and 41 patients met the severe pneumonia criteria. Apathogen was found in 20 community-acquired pneumonia (CAP) and 13 hospital-acquired pneumonia(HAP). The most frequently isolated pathogen from the sputum culture of patients with either severe CAPor HAP was Acinetobacter baumannii. The mortality rate of severe HAP patients was higher than thatof severe CAP patients (84% vs. 65%), but the difference was nonsignificant. Most of the subjects hadcomorbidities (CAP 75%, HAP 61.6%). Procalcitonin (PCT) and C-reactive protein (CRP) levels in severeCAP were higher than those in severe HAP (PCT 7.7 vs 6.0, p=0.658; CRP 163.1 vs 93.6, p=0.580), but thedifferences were also nonsignificant.Conclusion: The most frequently isolated pathogens from the sputum culture of patients with severepneumonia were Acinetobacter baumanii, which should be considered at the time of diagnosis and empiricalantibiotic therapy. Severe pneumonia was often accompanied by comorbidities, inflammation responsesincrease in both severe CAP and HAP with a high mortality rate.

Ceftobiprole and pneumonia in adults admitted to the emergency department is it time to assess a new therapeutic algorithm?

Objective Ceftobiprole is an advance generation cephalosporin which has broad-spectrum bacterial activity (both against Gram-positive and negative pathogens) and was approved for the treatment of community-acquired pneumonia (CAP) and non-ventilated hospital-acquired pneumonia (HAP) in most European countries. We aimed to evaluate the efficacy and safety of ceftobiprole in the treatment of pneumonia in a cohort of severely ill patients admitted to the emergency department (ED). Methods 1-year observational retrospective mono-centric study. Were defined two primary endpoints: first, to evaluate the clinical cure at the test-of-cure (TOC); the second, to evaluate the early improvement, defined as a reduction of symptoms and inflammatory parameters 72 hours after the start of treatment. The secondary endpoint is to evaluate the reduction of antibiotic “burden” using ceftobiprole despite standard of care in severe hospital-acquired pneumonia. Results During the study period, a total of 48 patients with severe pneumonia received ceftobiprole: twenty-two patients (45.8%) as empiric therapy, 9 (18.5%) as a de-escalation option from previous combination therapies, 13 patients (27.1%) as an escalation therapy from ceftriaxone or amoxicillin/clavulanate and four patients (8.3%) as a targeted therapy based on microbiological results. Ceftobiprole mean duration therapy was 10.2 days. Forty-six patients with severe pneumonia had an early clinical improvement 72 hours after the start of treatment (95.8%). In general, ceftobiprole was well tolerated; only one patient suspended the drug because of poor tolerability. The clinical cure at TOC was 85.4% and 30-days crude mortality was 10.4%. Conclusions This study confirms that ceftobiprole is effective in severely ill patients with pneumonia at risk of poor outcomes.

When are combinations of antibiotics clinically useful?

Antimicrobial resistance is a global crisis. Prescribing antibacterial combinations may be one way of reducing the development of resistance in target pathogens, as in the treatment of tuberculosis. Combinations may be useful for ascertaining synergy, broadening antimicrobial cover to reduce the risk of non-susceptibility, antimicrobial stewardship reasons, and immune modulation. The current research literature and/or prevailing global standards of clinical care suggest that combination therapy may be advantageous in: severe community-acquired pneumonia; severe hospital-acquired or ventilator-associated pneumonia or when there is a high risk of resistance in hospital-acquired or ventilator-associated pneumonia; multi-drug or extensively drug-resistant Gram-negative infections; and severe group A streptococcal infections. In other situations, combinations may be harmful. Overall, outside of tuberculosis, combination antibacterial therapy is likely to improve outcomes only in specific circumstances and there is little evidence to suggest that this prevents the development of bacterial resistance. Further high-quality research is essential.

Transcatheter Mitral Valve Implantation (TMVI) Using Edwards SAPIEN 3 Prostheses in Patients at Very High or Prohibitive Surgical Risk: A Single-Center Experience.

Background Mitral valve surgery in patients with failing bioprosthesis, annuloplasty rings, or in patients with advanced mitral annular calcification (MAC) is associated with high morbidity and mortality rates. Percutaneous antegrade transseptal transcatheter mitral valve implantation (TMVI) has recently successfully been performed in those patients at high or prohibitive surgical risk, but data on patients treated by TMVI are sparse. This study sought to evaluate short- and midterm outcomes of patients treated by TMVI at our site in clinical practice. Methods and Results From October 2016 to February 2018, seven patients (six women and one man) at high or prohibitive surgical risk underwent TMVI at our site. Three procedures were performed as TMVI in failed mitral valve bioprostheses (TMVI-VIV, “valve-in-valve”), one procedure was performed as TMVI in a failed mitral annuloplasty ring (TMVI-R), and three procedures were performed as TMVI in advanced native mitral annular calcification (TMVI-MAC). Mean age of the population treated was 77 ± 8.1 years, and mean log EuroScore I was 39 ± 0.12%. In all patients, an Edwards SAPIEN 3 transcatheter heart valve was implanted under 3D-TOE and fluoroscopic guidance using a transvenous/transseptal access. Indication for TMVI was the presence of advanced heart failure symptoms in all patients (NYHA class III/IV). The predominant dysfunction of the mitral valve treated was severe regurgitation in 72% (n = 5) and severe stenosis in 29% (n = 2) of all patients. TMVI was technically successful in all procedures. Clinical success with functional improvement of at least one NYHA class after procedure compared with before procedure was also achieved in all patients. Median NYHA class improved significantly from 4 before procedure to 2 after TMVI (p=0.008). Mitral valve regurgitation was reduced to trace or mild in all but one patient, who showed moderate MR after TMVI-MAC. No patient-prosthesis mismatch or LVOT obstruction occurred after TMVI. Two patients underwent interventional ASD closure during the in-hospital course due to a large and persisting atrial septal defect after transseptal access. One patient underwent pacemaker implantation due to complete AV-block after TMVI. One patient died in hospital 12 days after the procedure due to severe hospital-acquired pneumonia and sepsis. In-hospital mortality rate was 14% (1/7) in this high-risk population. After hospital discharge, no death occurred and clinical improvement—according to NYHA functional class—remained stable during one-year follow-up. Conclusion In this small single-center series, TMVI appears promising for patients at high or prohibitive surgical risk with either failing mitral bioprostheses/annuloplasty rings or native mitral valve dysfunction in combination with advanced MAC. Gaining experience in TMVI and new valves will further improve safety and efficacy of this new treatment option.

Hospital-acquired pneumonia - new guidelines

The role of multidrug-resistant (MDR) pathogens in nosocomial infections is increasing. However national data in Germany do not show significant changes in the spectrum of pathogens in hospital-acquired pneumonia (HAP). The assessment of individual risk factors for MDR pathogens remains central for the selection of empiric antimicrobial therapy. Thoracic ultrasound may be added as part of the diagnostic work-up and for the detection of complications. Procalcitonin and lactate testing are recommended for the diagnosis of sepsis/septic shock in addition to sepsis scores. Detection of influenza virus by PCR from respiratory samples is recommended during influenza season. Empiric combination therapy is only recommended for patients with severe HAP (invasive ventilation, septic shock) and high risk of infection with MDR pathogens, since combination therapy has only been shown to be superior in this situation. Deescalation according to clinical and microbiological criteria is highly recommended. In patients with septic organ dysfunction/septic shock antibiotic dosing of adequately choosen betalactams according to Pk/Pd criteria is endorsed. adjunctive aerosolised therapy should only be performed in experienced centres. This remains an option for patients with detection of MDR pathogens, who are not deemed successfully treatable with systemic therapy alone.

Treatment of severe hospital-acquired and ventilator-associated pneumonia: a systematic review of inclusion and judgment criteria used in randomized controlled trials

BackgroundHospital-acquired and ventilator-associated pneumonia (HAP/VAP) are often selected for randomized clinical trials (RCTs) aiming at new drug approval. Guidelines for the design of such RCTs have been repeatedly updated by regulatory agencies. We hypothesized that large variability in the enrolled populations, the endpoints assessed and the HAP/VAP definition criteria may impact the results of these studies, and addressed this through a systematic review of HAP/VAP RCTs.MethodsA search (Pubmed-Embase-ICAAC-ECCMID) of all RCTs published between 1994 and 2016 comparing antimicrobial treatment for HAP/VAP in the intensive care unit was conducted. The populations enrolled, inclusion/exclusion criteria, statistical design and endpoints assessed were recorded. All unpublished RCTs recorded on the ClinicalTrials.gov registry were also screened.ResultsFrom the 93 abstracts reviewed, 39 potentially relevant studies were inspected, leading to 27 studies being included. As expected, illness severity or the proportion with VAP (27–100%) differed greatly among the enrolled populations. The HAP/VAP definition used various clinical and biological criteria, and only 55% of studies required a microbiological sample. The mandatory duration of prior hospital stay was variable; the mechanical ventilation duration was an inclusion criterion in only 41% of VAP studies. Nine studies had non-inferiority design, but nine studies (33%) did not have a pre-specified statistical hypothesis. Clinical cure was the primary endpoint in 24 studies, but was recorded in several populations or as the co-primary endpoint in 13 studies. The definition of clinical cure and the timing of its assessment greatly differed. This variability slightly improved over time but remained significant in the 13 registered but currently unpublished RCTs that we screened.ConclusionOur study provides a description of populations and endpoints of RCTs evaluating antimicrobials for treatment of HAP/VAP in the ICU. There was significant heterogeneity in enrollment criteria, endpoints and statistical design, which may influence the ability of studies to demonstrate differences between studied drugs.

Viral infection is not uncommon in adult patients with severe hospital-acquired pneumonia.

BackgroundViral pathogens have not generally been regarded as important causes of severe hospital-acquired pneumonia (HAP), except in patients with hematologic malignancy or transplant recipients. We investigated the role and distribution of viruses in adult with severe HAP who required intensive care.MethodsFrom March 2010 to February 2012, adult patients with severe HAP required admission to the intensive care unit (ICU), 28-bed medical ICU in a tertiary care hospital, were prospectively enrolled. Respiratory viruses were detected using multiplex reverse-transcription polymerase chain reaction and/or shell vial culture.ResultsA total of 262 patients were enrolled and 107 patients (40.8%) underwent bronchoscopic BAL for etiologic diagnosis. One hundred and fifty-six patients (59.5%) had bacterial infections and 59 patients (22.5%) had viral infections. Viruses were detected in BAL fluid specimens of 37 patients (62.7%, 37/59). The most commonly identified viruses were respiratory syncytial virus and parainfluenza virus (both 27.1%, 16/59), followed by rhinovirus (25.4%, 15/59), and influenza virus (16.9%, 10/59). Twenty-one patients (8.0%, 21/262) had bacterial-viral coinfections and Staphylococcus aureus was the most commonly coexisting bacteria (n = 10). Viral infection in non-immunocompromised patients was not uncommon (11.1%, 16/143), although it was not as frequent as that in immunocompromised patients (36.4%, 43/119). Non-immunocompromised patients were significantly older than immunocompromised patients and had significantly higher rates of underlying chronic obstructive pulmonary disease, tuberculous destroyed lung and chronic kidney disease. The 28 day mortalities of patients with bacterial infections, viral infections and bacterial-viral coinfections were not significantly different (29.5%, 35.6% and 19.0%, respectively; p = 0.321).ConclusionsViral pathogens are not uncommon in adult patients with severe HAP who required ICU admission. Since viral pathogens may cause severe HAP and could be a potential source of viral transmission, further investigation is required to delineate the role of viral pathogens in severe HAP.

Pharmaceutical care on a patient with severe hospital-acquired pneumonia

Pharmaceutical care on a patient with severe hospital-acquired pneumonia

The Impact of Serum Vancomycin Levels and Minimum Inhibitory Concentrations of Methicillin‐Resistant Staphylococcus aureus on Mortality in Patients with Nosocomial Pneumonia

Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure is not uncommon, even when the minimum inhibitory concentration (MIC) of the MRSA strain is within the susceptible range for vancomycin. To describe the relationship between molecular markers such as the mecA and agrII genes, serum vancomycin levels and vancomycin MICs, and the 30-day mortality rate of patients with nosocomial MRSA pneumonia in an intensive care unit (ICU). The present study was a prospective cohort study including all patients with MRSA hospital-acquired pneumonia or ventilator-associated pneumonia who were admitted to the ICU of a tertiary care hospital between June 2009 and December 2011. The MIC for vancomycin was determined using the E-test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the Acute Physiology and Chronic Health Evaluation II (APACHE) score and the presence of the agrII gene. The primary outcome was mortality at 30 days. Thirty-six (42.4%) patients died within 30 days of the index MRSA culture. A multiple regression analysis that included the variables of MIC (determined using the E-test or broth microdilution methods), APACHE II score, serum vancomycin level and the presence of agrII revealed that only the APACHE II score was related to the 30-day mortality rate (P=0.03). Seven patients (9.0%) with isolates exhibiting an MIC ≥1.5 μg/mL according to the E-test method died, and nine patients (11.6%) survived (P=0.76). Of the patients for whom MICs were determined using the broth microdilution method, 11 (14.1%) patients with MICs of 1.0 μg/mL died, and 16 (20.5%) survived (P=0.92). The median APACHE II score of survivors was 22.5, and the median score of nonsurvivors was 25.0 (P=0.03). The presence of the agrII gene was not related to the 30-day mortality rate. Patients with severe hospital-acquired pneumonia presented with MRSA isolates with low to intermediate vancomycin MICs in the ICU setting. At the Hospital de Clínicas de Porto Alegre (Porto Alegre, Brazil), the 30-day mortality rate was high, and was similar among patients with severe hospital-acquired pneumonia infected with MRSA isolates that exhibited MICs of ≤1.5 μg/mL determined using the E-test method and ≤1.0 μg/mL determined using the broth microdilution method in those who achieved optimal serum vancomycin levels. The APACHE II scores which provides an overall estimate of ICU mortality were independently associated with mortality in the present study, regardless of the MICs determined. Molecular markers, such as the agrII gene, were not associated with higher mortality in the present study.