Hospital-acquired bacterial pneumonia in critically ill patients: from research to clinical practice.

INTRODUCTION: Hospital-acquired pneumonia (HAP) represents a significant cause of mortality among critically ill patients admitted to Intensive Care Units (ICUs). Timely and precise diagnosis is imperative to enhance therapeutic efficacy and patient outcomes. However, the diagnostic process is challenged by test limitations and a wide-ranging list of differential diagnoses, particularly in patients exhibiting escalating oxygen requirements, leukocytosis, and increased secretions. AREAS COVERED: This narrative review aims to update diagnostic modalities, facilitating the prompt identification of nosocomial pneumonia while guiding, developing, and assessing therapeutic interventions. A comprehensive literature review was conducted utilizing the MEDLINE/PubMed database from 2013 to April 2024. EXPERT OPINION: An integrated approach that integrates clinical, microbiological, and imaging tools is paramount. Progress in diagnostic techniques, including novel molecular methods, the expanding utilization and accuracy of bedside ultrasound, and the emergence of Artificial Intelligence, coupled with an improved comprehension of lung microbiota and host-pathogen interactions, continues to enhance our capability to accurately and swiftly identify HAP and its causative agents. This advancement enables the refinement of treatment strategies and facilitates the implementation of precision medicine approaches.

Clinical challenge of diagnosing non-ventilator hospital-acquired pneumonia and identifying causative pathogens: a narrative review.

Non-ventilated hospital-acquired pneumonia (NV-HAP) is associated with a significant healthcare burden, arising from high incidence and associated morbidity and mortality. However, accurate identification of cases remains challenging. At present, there is no gold-standard test for the diagnosis of NV-HAP, requiring instead the blending of non-specific signs and investigations. Causative organisms are only identified in a minority of cases. This has significant implications for surveillance, patient outcomes and antimicrobial stewardship. Much of the existing research in HAP has been conducted among ventilated patients. The paucity of dedicated NV-HAP research means that conclusions regarding diagnostic methods, pathology and interventions must largely be extrapolated from work in other settings. Progress is also limited by the lack of a widely agreed definition for NV-HAP. The diagnosis of NV-HAP has large scope for improvement. Consensus regarding a case definition will allow meaningful research to improve understanding of its aetiology and the heterogeneity of outcomes experienced by patients. There is potential to optimize the role of imaging and to incorporate novel techniques to identify likely causative pathogens. This would facilitate both antimicrobial stewardship and surveillance of an important healthcare-associated infection. This narrative review considers the utility of existing methods to diagnose NV-HAP, with a focus on the significance and challenge of identifying pathogens. It discusses the limitations in current techniques, and explores the potential of emergent molecular techniques to improve microbiological diagnosis and outcomes for patients.

Application of a multiplex molecular pneumonia panel and real-world impact on antimicrobial stewardship among patients with hospital-acquired and ventilator-associated pneumonia in intensive care units.

BACKGROUND: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship. METHODS: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP. RESULTS: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results. CONCLUSIONS: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.

Perspectives on the use of ceftolozane/tazobactam: a review of clinical trial data and real-world evidence.

Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are common healthcare-associated infections linked to high morbidity and mortality. Gram-negative pathogens, such as Pseudomonas aeruginosa, exhibit multidrug resistance and are recognized as major public health concerns, particularly among critically ill patients with HABP/VABP. Ceftolozane/tazobactam is a novel combination antibacterial agent comprising ceftolozane (a potent antipseudomonal cephalosporin) and tazobactam (a ß-lactamase inhibitor). Phase III trials have demonstrated non-inferiority of ceftolozane/tazobactam to comparators, leading to the approval of ceftolozane/tazobactam for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and nosocomial pneumonia. In this article, we review the clinical trial evidence and key real-world effectiveness data of ceftolozane/tazobactam for the treatment of serious healthcare-associated Gram-negative infections, focusing on patients with HABP/VABP.

Highlights from a review of ceftolozane/tazobactam for the treatment of serious infectionsSerious infections that can affect people in hospitals can cause serious illness or loss of life. Antibiotics are a type of medicine designed to kill the bacteria that cause these infections. However, bacteria have evolved over time, which means that antibiotics are not as effective at killing the bacteria and treating the infection. This is known as antibiotic resistance. To treat serious infections in hospital, there is a need for new antibiotics that can overcome this resistance and successfully fight off bacteria. This paper looks at an antibiotic known as ceftolozane/tazobactam (C/T), which can be used to treat people with serious infections that are picked up in hospitals. Clinical and laboratory studies have been reviewed to evaluate how effective, safe, and suitable C/T is for patients. The studies discussed in this paper highlight how well C/T works in people with serious infections, including those who are already ill and have been put on a ventilator to help with their breathing. Some of these studies showed that C/T worked well against lots of different types of bacteria that are known to cause serious infections in hospital and are linked to a high risk of death. Antibiotic resistance is a major problem all over the world. There is a need for effective antibiotics that can treat a range of infections caused by resistant bacteria. The results of this paper show that there is a lot of evidence to support the use of C/T in hospitals for people with serious bacterial infections.

Efficacy and safety of lascufloxacin for nursing- and healthcare-associated pneumonia: A single-arm, open-label clinical trial.

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.

Identification and detection of pathogenic bacteria from patients with hospital-acquired pneumonia in southwestern Iran; evaluation of biofilm production and molecular typing of bacterial isolates.

BACKGROUND: Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection in intensive care units (ICUs). The present study aims to determine the prevalence of pathogenic bacteria, their biofilm formation, and molecular typing from patients with HAP in southwestern Iran. METHODS: Fifty-eight patients with HAP participated in this cross-sectional study. Sputum and endotracheal aspirate were collected from each patient for isolation and detection of bacteria. Biofilm formation was evaluated using Congo red agar or Microtiter plate assay. The antimicrobial susceptibility patterns of the isolates were investigated. The multiplex polymerase chain reaction (M-PCR) technique was used to determine the Staphylococcal Cassette Chromosome mec (SCCmec) types of methicillin-resistant Staphylococcus aureus (MRSA) strains. All S. aureus isolates were typed using the agr typing method. A repetitive element sequence-based PCR (rep-PCR) typing method was used for typing of Gram-negative bacteria. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) software version 15 and the chi-square test. RESULTS: Bacteria were isolated in 52 (89.7%) of patients. Acinetobacter baumannii (A. baumannii) was the most prevalent organism (37%), followed by S. aureus, Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli). Using the PCR method, 56 bacteria were detected. A. baumannii was the most prevalent (35.7%) organism. A. baumannii and P. aeruginosa were biofilm-producing. All Gram-negative isolates were colistin-sensitive, and most of the A. baumannii isolates were multidrug-resistant (MDR). MRSA was identified in 12 (80%) S. aureus isolates, and 91.6% of MRSA were SCCmec type III. The agr type III was the most predominant. The rep-PCR analysis showed seven different patterns in 20 A. baumannii, six patterns in 13 P. aeruginosa, and four patterns in 6 E. coli. CONCLUSION: A. baumannii was more prevalent than S. aureus in ventilator-associated pneumonia (VAP), while S. aureus is a major pathogen in non-ventilator hospital-acquired pneumonia (NV-HAP), possibly due to the tendency of the former to aquatic environments. Based on the rep-PCR typing method, it was concluded that bacteria were transmitted from patients or healthcare workers among different wards. Colistin can be used as a treatment in Gram-negative MDR isolates.

Association between mortality and highly antimicrobial-resistant bacteria in intensive care unit-acquired pneumonia.

Data on the relationship between antimicrobial resistance and mortality remain scarce, and this relationship needs to be investigated in intensive care units (ICUs). The aim of this study was to compare the ICU mortality rates between patients with ICU-acquired pneumonia due to highly antimicrobial-resistant (HAMR) bacteria and those with ICU-acquired pneumonia due to non-HAMR bacteria. We conducted a multicenter, retrospective cohort study using the French National Surveillance Network for Healthcare Associated Infection in ICUs ("REA-Raisin") database, gathering data from 200 ICUs from January 2007 to December 2016. We assessed all adult patients who were hospitalized for at least 48 h and presented with ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii. The association between pneumonia caused by HAMR bacteria and ICU mortality was analyzed using the whole sample and using a 1:2 matched sample. Among the 18,497 patients with at least one documented case of ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii, 3081 (16.4%) had HAMR bacteria. The HAMR group was associated with increased ICU mortality (40.3% vs. 30%, odds ratio (OR) 95%, CI 1.57 [1.45-1.70], P < 0.001). This association was confirmed in the matched sample (3006 HAMR and 5640 non-HAMR, OR 95%, CI 1.39 [1.27-1.52], P < 0.001) and after adjusting for confounding factors (OR ranged from 1.34 to 1.39, all P < 0.001). Our findings suggest that ICU-acquired pneumonia due to HAMR bacteria is associated with an increased ICU mortality rate, ICU length of stay, and mechanical ventilation duration.

The clinical role of host and bacterial-derived extracellular vesicles in pneumonia.

Pneumonia is among the leading causes of morbidity and mortality worldwide. Due to constant evolution of respiratory bacteria and viruses, development of drug resistance and emerging pathogens, it constitutes a considerable health care threat. To enable development of novel strategies to control pneumonia, a better understanding of the complex mechanisms of interaction between host cells and infecting pathogens is vital. Here, we review the roles of host cell and bacterial-derived extracellular vesicles (EVs) in these interactions. We discuss clinical and experimental as well as pathogen-overarching and pathogen-specific evidence for common viral and bacterial elicitors of community- and hospital-acquired pneumonia. Finally, we highlight the potential of EVs for improved management of pneumonia patients and discuss the translational steps to be taken before they can be safely exploited as novel vaccines, biomarkers, or therapeutics in clinical practice.

Research on the economic loss of hospital-acquired pneumonia caused by Klebsiella pneumonia base on propensity score matching.

BACKGROUND: Hospital-acquired pneumonia (HAP) caused by Klebsiella pneumonia (KP) is a common nosocomial infection (NI). However, the reports on the economic burden of hospital-acquired pneumonia caused by Klebsiella pneumonia (KP-HAP) were scarce. The study aims to study the direct economic loss caused by KP-HAP with the method of propensity score matching (PSM) to provide a basis for the cost accounting of NI and provide references for the formulation of infection control measures. METHODS: A retrospective investigation was conducted on the hospitalization information of all patients discharged from a tertiary group hospital in Shenzhen, Guangdong province, China, from June 2016 to August 2019. According to the inclusion and exclusion criteria, patients were divided into the HAP group and noninfection group, the extended-spectrum beta-lactamases (ESBLs) positive KP infection group, and the ESBLs-negative KP infection group. After the baselines of each group were balanced with the PSM, length of stay (LOS) and hospital cost of each group were compared. RESULTS: After the PSM, there were no differences in the baselines of each group. Compared with the noninfection group, the median LOS in the KP-HAP group increased by 15 days (2.14 times), and the median hospital costs increased by 7329 yuan (0.89 times). Compared with the ESBLs-negative KP-HAP group, the median LOS in the ESBLs-positive KP-HAP group increased by 7.5 days (0.39 times), and the median hospital costs increased by 22,424 yuan (1.90 times). CONCLUSION: KP-HAP prolonged LOS and increased hospital costs, and HAP caused by ESBLs-positive KP had more economic losses than ESBLs-negative, which deserves our attention and should be controlled by practical measures.

Headspace analyses using multi-capillary column-ion mobility spectrometry allow rapid pathogen differentiation in hospital-acquired pneumonia relevant bacteria.

BACKGROUND: Hospital-acquired pneumonia (HAP) is a common problem in intensive care medicine and the patient outcome depends on the fast beginning of adequate antibiotic therapy. Until today pathogen identification is performed using conventional microbiological methods with turnaround times of at least 24 h for the first results. It was the aim of this study to investigate the potential of headspace analyses detecting bacterial species-specific patterns of volatile organic compounds (VOCs) for the rapid differentiation of HAP-relevant bacteria. METHODS: Eleven HAP-relevant bacteria (Acinetobacter baumanii, Acinetobacter pittii, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Serratia marcescens) were each grown for 6 hours in Lysogeny Broth and the headspace over the grown cultures was investigated using multi-capillary column-ion mobility spectrometry (MCC-IMS) to detect differences in the VOC composition between the bacteria in the panel. Peak areas with changing signal intensities were statistically analysed, including significance testing using one-way ANOVA or Kruskal-Wallis test (p < 0.05). RESULTS: 30 VOC signals (23 in the positive ion mode and 7 in the negative ion mode of the MCC-IMS) showed statistically significant differences in at least one of the investigated bacteria. The VOC patterns of the bacteria within the HAP panel differed substantially and allowed species differentiation. CONCLUSIONS: MCC-IMS headspace analyses allow differentiation of bacteria within HAP-relevant panel after 6 h of incubation in a complex fluid growth medium. The method has the potential to be developed towards a feasible point-of-care diagnostic tool for pathogen differentiation on HAP.

Evaluating the emergence of nonsusceptibility among Pseudomonas aeruginosa respiratory isolates from a phase-3 clinical trial for treatment of nosocomial pneumonia (ASPECT-NP).

OBJECTIVES: The emergence of nonsusceptibility to ceftolozane/tazobactam and meropenem was evaluated among Pseudomonas aeruginosa (P. aeruginosa) lower respiratory tract isolates obtained from participants in the ASPECT-NP clinical trial. METHODS: ASPECT-NP was a phase-3, randomised, double-blind, multicentre trial that demonstrated noninferiority of 3 g ceftolozane/tazobactam q8h versus 1 g meropenem q8h for treatment of ventilated hospital-acquired/ventilator-associated bacterial pneumonia. Molecular resistance mechanisms among postbaseline nonsusceptible P. aeruginosa isolates and clinical outcomes associated with participants with emergence of nonsusceptibility were examined. Baseline susceptible and postbaseline nonsusceptible P. aeruginosa isolate pairs from the same participant underwent molecular typing. RESULTS: Emergence of nonsusceptibility was not observed among the 59 participants with baseline susceptible P. aeruginosa isolates in the ceftolozane/tazobactam arm. Among 58 participants with baseline susceptible P. aeruginosa isolates in the meropenem arm, emergence of nonsusceptibility was observed in 13 (22.4%). Among participants who received ceftolozane/tazobactam and meropenem, 5.1% and 3.4% had a new infection with a nonsusceptible strain, respectively. None of the isolates with emergence of nonsusceptibility to meropenem developed co-resistance to ceftolozane/tazobactam. The molecular mechanisms associated with emergence of nonsusceptibility to meropenem were decreased expression or loss of OprD and overexpression of MexXY. CONCLUSIONS: Among participants with emergence of nonsusceptibility to meropenem, clinical outcomes were similar to overall clinical outcomes in the ASPECT-NP meropenem arm. Ceftolozane/tazobactam was more stable to emergence of nonsusceptibility versus meropenem; emergence of nonsusceptibility was not observed in any participants with baseline susceptible P. aeruginosa who received ceftolozane/tazobactam in ASPECT-NP.

Safety considerations of current drug treatment strategies for nosocomial pneumonia.

Introduction: Nosocomial pneumonia unfortunately remains a frequent event for which appropriate antibiotic treatment is central to improving outcomes. Physicians must choose an early and appropriate empirical treatment, basing their decision on the safety profile and possible side effects. Areas covered: In this review, we analyzed the safety profiles of the most common antimicrobials for treating nosocomial pneumonia. Beta-lactams are used most often for these infections, with a high percentage (6% to 25%) of patients reporting allergy or hypersensitivity reactions; however, exhaustive evaluation is key because it seems possible to de-label as many as 90% by proper assessment. Combinations including a beta-lactam are recommended in patients with risk factors for drug-resistant microorganisms and septic shock. Although aminoglycosides are safe for 3-5 days of therapy, renal function should be monitored. Fluoroquinolones must also be used with care given the risk of collagen degradation and cardiovascular events, mainly aneurysm or aortic dissection. Linezolid or vancomycin are both viable for the treatment of methicillin-resistant Staphylococcus aureus, but linezolid seems to be the superior option. Antibiotic stewardships programs must be developed for each center. Expert opinion: Choosing the most appropriate antimicrobial based on information from national and international guidelines, local microbiology data, and stewardship programs may reduce the use of broad-spectrum antibiotics. Daily assessment for the emergence of adverse events related to antimicrobial use is essential.

Autophagy suppression plays a role in parenteral nutrition-associated lung injury.

BACKGROUND & AIMS: The long-term usage of parenteral nutrition (PN) is associated with the increased incidence of pneumonia. Few studies have focused on the pathogenesis of PN-associated lung injury (PNLI). Previous studies have found that autophagy suppression may be an important mechanism for PN-associated complications. The present study aimed to investigate the effect of PN on lung barrier impairment and its association with autophagy. METHODS: We retrospectively identified intestinal failure patients admitted to a clinical nutrition service center to determine the morbidity of hospital-acquired pneumonia (HAP) and its association with PN. In animal studies, we established the PNLI mouse model to measure severity of lung injury, lung barrier, pulmonary microbiota in bronchoalveolar fluid (BALF), levels of autophagy and apoptosis, and the inflammatory signaling pathway. RESULT: Among the 259 patients, 37 (14.3%) patients developed HAP. Multivariate analysis revealed that prolonged PN was an independent predictor for HAP. In animal studies, we found that PN impaired the lung barrier and disturbed pulmonary microbiota homeostasis. The abundance of Actinomycetes and Firmicutes phyla in BALF were significantly increased, while the Bacteroidetes phylum decreased. Bacterial translocations in the lung were observed by fluorescence in situ hybridization. PN caused autophagy suppression and activated the apoptosis level and inflammatory HMGB1/RAGE/NF-kB signaling pathway. The intervention of exogenous rapamycin can attenuate the impairment of the lung barrier, reduce apoptosis and inhibit inflammatory signaling by upregulation of autophagy. CONCLUSION: PN had a damaging effect on the lung barrier, disturbed pulmonary microbiota homeostasis, and induced bacterial translocation. Autophagy suppression might be a crucial mechanism in inducing PNLI.

SARS-CoV-2-related pneumonia cases in pneumonia picture in Russia in March-May 2020: Secondary bacterial pneumonia and viral co-infections.

BACKGROUND: We are communicating the results of investigating statistics on SARS-CoV-2-related pneumonias in Russia: percentage, mortality, cases with other viral agents, cases accompanied by secondary bacterial pneumonias, age breakdown, clinical course and outcome. METHODS: We studied two sampling sets (Set 1 and Set 2). Set 1 consisted of results of testing 3382 assays of out-patients and hospital patients (5-88 years old) with community-acquired and hospital-acquired pneumonia of yet undetermined aetiology. Set 2 contained results of 1204 assays of hospital patients (12-94 years old) with pneumonia and COVID-19 already diagnosed by molecular biological techniques in test laboratories. The results were collected in twelve Russian cities/provinces in time range 2 March - 5 May 2020. Assays were analysed for 10 bacterial, 15 viral, 2 fungal and 2 parasitic aetiological agents. RESULTS: In Set 1, 4.35% of total pneumonia cases were related to SARS-CoV-2, with substantially larger proportion (18.75%) of deaths of pneumonia with COVID-19 diagnosed. However, studying Set 2, we revealed that 52.82% patients in it were also positive for different typical and atypical aetiological agents usually causing pneumonia. 433 COVID-19 patients (35.96%) were tested positive for various bacterial aetiological agents, with Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae infections accounting for the majority of secondary pneumonia cases. CONCLUSIONS: SARS-CoV-2, a low-pathogenic virus itself, becomes exceptionally dangerous if secondary bacterial pneumonia attacks a COVID-19 patient as a complication. An essential part of the severest complications and mortality associated with COVID-19 in Russia in March-May 2020, may be attributed to secondary bacterial pneumonia and to a much less extent viral co-infections. The problem of hospital-acquired bacterial infection is exceptionally urgent in treating SARS-CoV-2 patients. The risk of secondary bacterial pneumonia and its further complications, should be given very serious attention in combating SARS-CoV-2.

Nosocomial Infections: A History of Hospital-Acquired Infections.

In the United States, healthcare acquired infections (HAIs) or nosocomial infections are the sixth leading cause of death. This article reviews the history, prevalence, economic costs, morbidity and mortality, and risk factors associated with HAIs. Types of infections described include bacterial, fungal, viral, and multidrug resistant infections that contribute to the most common causes of HAIs, which include catheter- associated urinary tract infections, hospital-acquired pneumonias, bloodstream infections, and surgical site infections. Most nosocomial infections are preventable and monitoring and prevention strategies are described.

Diagnostic accuracy of Gram staining when predicting staphylococcal hospital-acquired pneumonia and ventilator-associated pneumonia: a systematic review and meta-analysis.

BACKGROUND: There is no clear guidance on empirical antibiotic coverage against Staphylococcus aureus for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). OBJECTIVE: To evaluate whether the presence of clusters of Gram-positive cocci in Gram staining of respiratory samples predicts S. aureus as HAP/VAP pathogen. METHODS: Data sources were MEDLINE, PubMed, Embase, Scielo, CINAHL and Scopus, from inception to 15/07/2017 (update on 31/10/2019), and original data from a single-centre database (PROSPERO: CRD42017072138). We included studies reporting the diagnostic accuracy of a Gram-staining evaluation suggestive of Staphylococcus compared with a positive culture for S. aureus in any type of lower respiratory tract sample. Participants were adult patients with HAP/VAP. The index test was morphological evaluation of Gram staining of respiratory samples. We followed PRISMA guidelines and assessed risk of bias and applicability with the QUADAS-2 tool. We conducted a meta-analysis using a bivariate random effects model. RESULTS: We selected five studies that included only VAP and data from a single-centre database including VAP and HAP. We pooled six studies for VAP and analysed 1665 respiratory samples. Pooled sensitivity was 68% (95%CI 49-83 and specificity 95% (95%CI 86-98). The pooled positive likelihood ratio was 12.7 (95%CI 5.1-31.6), negative likelihood ratio 0.34 (95%CI 0.20-0.57), diagnostic odds ratio 38 (95%CI 13-106) and area under the summary receiver operating curve (SROC) 0.91 (95%CI 0.88-0.93). There was great heterogeneity between sensitivity and specificity. In scenarios in which the prevalence of S. aureus was between 5% and 20%, the positive and negative predictive values were 62% (95%CI 47-77) and 95% (95%CI 82-100), respectively. CONCLUSIONS: Detection of Gram-positive cocci in clusters in respiratory samples of patients with VAP has the potential to guide risk assessments of S. aureus for more personalized antibiotic coverage. Randomized clinical trials with patient-centred outcomes are needed for strong clinical recommendations.

Ceftolozane and tazobactam for the treatment of hospital acquired pneumonia.

INTRODUCTION: Patients admitted to hospitals are at risk of developing nosocomial infections. These types of infections typically occur in immune-compromised patients. Furthermore, nosocomial infections are frequently caused by resistant organisms, including nonfermenting gram-negative bacilli such as Pseudomonas aeruginosa. AREAS COVERED: P. aeruginosa is a hazardous pathogen. It can resist numerous antibiotics, due to several resistance mechanisms. It is associated with serious illnesses, particularly hospital-acquired infections including ventilator-associated pneumonia. In the past, only a limited number of anti-pseudomonal drugs were available. However, several therapeutic advancements have been made, in recent years, to target P. aeruginosa, including the development of the new cephalosporin: ceftolozane-tazobactam. EXPERT OPINION: Ceftolozane-tazobactam is a combination of a novel semi-synthetic fifth-generation cephalosporin with a well-established beta-lactamase inhibitor. From a structural perspective, ceftolozane-tazobactam has attested increased stability to AmpC ß-lactamases. Additionally, ceftolozane-tazobactam is less affected by changes in efflux pumps and porin permeability due to an enhanced affinity to certain penicillin-binding proteins (PBPs). This enables the molecule to overcome the most common anti-drug resistant mechanisms of bacteria. According to previous clinical trials conducted, ceftolozane-tazobactam must be considered when treating patients with confirmed or suspected P. aeruginosa respiratory tract infections, either nosocomial pneumonia or ventilator-associated pneumonia.

Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in a Chinese adult: A case report.

RATIONALE: Methicillin-resistant Staphylococcus aureus (MRSA) has been established as an important cause of severe community-acquired pneumonia (CAP) with very high mortality. Panton-Valentine leukocidin (PVL) producing MRSA has been reported to be associated with necrotizing pneumonia and worse outcome. The incidence of community-acquired MRSA (CA-MRSA) pneumonia is very low, as only a few CA-MRSA pneumonia cases were reported in the last few years. We present a case of severe CAP caused by PVL-positive MRSA with ensuing septic shock. PATIENT CONCERNS: A 68-year-old male with no concerning medical history had developed a fever that reached 39.0°C, a productive cough that was sustained for 5 days, and hypodynamia. He was treated with azithromycin and alexipyretic in a nearby clinic for 2 days in which the symptoms were alleviated. However, 1 day later, the symptoms worsened, and he was taken to a local Chinese medicine hospital for traditional medicine treatment. However, his clinical condition deteriorated rapidly, and he then developed dyspnea and hemoptysis. DIAGNOSIS: CA-MRSA pneumonia and septic shock. The sputum culture showed MRSA. Polymerase chain reaction of MRSA isolates was positive for PVL genes. INTERVENTIONS: Mechanical ventilation, fluid resuscitation, and antibiotic therapy were performed. Antibiotic therapy included mezlocillin sodium/sulbactam sodium, linezolid, and oseltamivir. OUTCOMES: He died after 12 hours of treatment. LESSONS: This is a report of severe pneumonia due to PVL-positive CA-MRSA in a healthy adult. CA-MRSA should be considered a pathogen of severe CAP, especially when combined with septic shock in previously healthy individuals.

The effect of oral care intervention on pneumonia hospitalization, Staphylococcus aureus distribution, and salivary bacterial concentration in Taiwan nursing home residents: a pilot study.

BACKGROUND: Elevated Staphylococcus aureus and oral bacterial concentrations are known to correlate with pneumonia hospitalization in nursing home residents. However, the effects of a professional oral care intervention on these factors remain unclear. The aims of this quasi-experimental study were to compare bacterial concentrations in saliva and sputum, oral health status, distribution of Staphylococcus aureus, and pneumonia status before and after a professional oral care intervention. METHODS: A purposive sample of residents from two nursing homes was divided into an intervention group that received a weekly professional oral care intervention and a control group. Oral bacterial concentration was determined by real-time polymerase chain reaction. The Staphylococcus aureus distribution was determined by bacterial culture and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. After data collection, a statistical analysis was performed to evaluate the effect of the intervention. RESULTS: Most residents were unconscious (80%), and most had a history of pneumonia (76%). Baseline demographic data did not significantly differ between the two groups. After the intervention, the intervention group had significant improvements in plaque index (1.66 ± 0.78 vs. 0.94 ± 0.64, p <  0.01), gingival index (2.36 ± 0.76 vs. 1.65 ± 0.83, p <  0.01), tongue coating index (0.96 ± 1.10 vs. 0.16 ± 0.47, p <  0.01), distribution of Staphylococcus aureus in salivary samples (11.11 ± 14.47% vs. 1.74 ± 3.75%, p = 0.02), and salivary bacterial concentration ([4.27 ± 3.65] × 105 vs. [0.75 ± 1.20] × 105, p <  0.01). Sputum bacterial concentration did not significantly differ. The intervention group also had a significantly lower annual prevalence of pneumonia hospitalization (1.24 ± 1.51 vs. 0.48 ± 0.59, p = 0.01), especially in residents whose salivary bacterial concentration exceeded the median. However, the duration of pneumonia hospitalization did not significantly differ between the two groups. CONCLUSION: A professional oral care intervention in nursing home residents can improve oral health, reduce levels of salivary bacteria and Staphylococcus aureus, and decrease the annual prevalence of pneumonia hospitalization. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov, NCT03874962. Registered 12 March 2019 - Retrospectively registered.

Molecular characterization of methicillin-resistant Staphylococcus aureus clinical strains from the endotracheal tubes of patients with nosocomial pneumonia.

BACKGROUND: Among all cases of nosocomial pneumonia, Staphylococcus aureus is the second most prevalent pathogen (17.8%). In Europe, 29.9% of the isolates are oxacillin-resistant. The changing epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial infections and the decreasing susceptibility to first-line antibiotics leave clinicians with few therapeutic options. The objective of our study was to determine the antimicrobial susceptibility, the associated molecular mechanisms of resistance and the epidemiological relatedness of MRSA strains isolated from the endotracheal tubes (ETT) of intubated critically ill patients in the intensive care unit (ICU) with nosocomial pneumonia caused by Staphylococcus aureus. METHODS: The antimicrobial susceptibility to vancomycin, linezolid, ciprofloxacin, clindamycin, erythromycin, chloramphenicol, fusidic acid, gentamicin, quinupristin-dalfopristin, rifampicin, sulfamethoxazole/trimethoprim, and tetracycline were measured. Resistance mechanisms were then analyzed by polymerase chain reaction and sequencing. Molecular epidemiology was carried out by multi-locus sequence typing. RESULTS: S. aureus isolates were resistant to ciprofloxacin, erythromycin, gentamicin, tetracycline, clindamycin, and fusidic acid. The most frequent mutations in quinolone-resistant S. aureus strains were S84L in the gyrA gene, V511A in the gyrB gene, S144P in the grlA gene, and K401R/E in the grlB gene. Strains resistant to erythromycin carried the ermC, ermA, and msrA genes; the same ermC and ermA genes were detected in strains resistant to clindamycin. The aac(6')-aph(2″) gene was related to gentamicin resistance, while resistance to tetracycline was related to tetK (efflux pump). The fusB gene was detected in the strain resistant to fusidic acid. The most frequent sequence types were ST22, ST8, and ST217, which were distributed in four clonal complexes (CC5, CC22, CC45, and CC59). CONCLUSIONS: High levels of resistance to second-line antimicrobials threatens the treatment of nosocomial respiratory infections due to methicillin-resistant S. aureus with decreased susceptibility to linezolid and vancomycin. The wide genotypic diversity found reinforces the central role of ICU infection control in preventing nosocomial transmission.