Septicaemia likely results in high case-fatality rates in the present multidrug-resistant (MDR) era. Amongst them are hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), two frequent fatal septicaemic entities amongst hospitalised patients. We reviewed the PubMed database to identify the common organisms implicated in HAP/VAP, to explore the respective risk factors, and to find the appropriate antibiotic choice. Apart from methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Enterobacteriaceae spp., MDR or extensively drug-resistant (XDR)-Acinetobacter baumannii complex spp., followed by Stenotrophomonas maltophilia, Chryseobacterium indologenes, and Elizabethkingia meningoseptica are ranked as the top Gram-negative bacteria (GNB) implicated in HAP/VAP. Carbapenem-resistant Enterobacteriaceae notably emerged as an important concern in HAP/VAP. The above-mentioned pathogens have respective risk factors involved in their acquisition. In the present XDR era, tigecycline, colistin, and ceftazidime-avibactam are antibiotics effective against the Klebsiella pneumoniae carbapenemase and oxacillinase producers amongst the Enterobacteriaceae isolates implicated in HAP/VAP. Antibiotic combination regimens are recommended in the treatment of MDR/XDR-P. aeruginosa or A. baumannii complex isolates. Some special patient populations need prolonged courses (>7-day) and/or a combination regimen of antibiotic therapy. Implementation of an antibiotic stewardship policy and the measures recommended by the United States (US) Institute for Healthcare were shown to decrease the incidence rates of HAP/VAP substantially.

To compare the clinical efficacy between salvage antimicrobial regimen consisting of tigecycline plus extended-infusion imipenem/cilastatin (TIC) and regimen of sulbactam plus imipenem/cilastatin (SIC) for patients with ventilator-associated pneumonia and pneumonic bacteremia due to extensively drug-resistant (XDR) Acinetobacter baumannii (Ab) isolates, and determine the correlation of results of in vitro tigecycline-imipenem synergy test with clinical efficacy. The comparative survey was conducted at a medical center in Taiwan in 2013. Patients comprising the TIC group (n = 28) received tigecycline plus extended-infusion imipenem/cilastatin following unresponsiveness to 3-day sulbactam-imipenem/cilastatin therapy, and those in the SIC group (n = 56) received sulbactam-imipenem/cilastatin throughout the course. Univariate and multivariate analyses were applied to explore 30-day case-fatality independent predictors. Additionally, the checkerboard test and time-kill analysis were performed for the bloodstream XDR-Ab isolates from patients in the TIC group, and molecular characterization was done for the bloodstream XDR-Ab strains of all patients. We found that the TIC scheme has a significant benefit on improving patients' survival status (the mortality rate of TIC and SIC group patients was 14.3% and 64.3%, respectively), corresponding well with in vitro synergy or additivity results by the checkerboard test. Twenty TIC group cases had monomicrobial XDR-Ab cultured from tracheal aspirates after 10 days of tigecycline-imipenem/cilastatin therapy, but none developed subsequent pneumonia. However, breakthrough primary Burkholderia cepacia (n = 3) and Pseudomonas aeruginosa (n = 1) bacteremias were attributed to four TIC case fatalities. Shock, SIC regimen usage, and development of breakthrough bacteremia were independent predictors of 30-day in-hospital mortality. Although the TIC regimen showed good efficacy, its value regarding managing XDR-Ab ventilator-associated pneumonia bacteremia needs further evaluation.

Few therapeutic options exist for various infections caused by extensively drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (XDR-Acb) complex isolates, including pneumonia. This study investigated the clinical efficacy between aerosolized colistimethate sodium (AS-CMS, 2 million units thrice a day) treatment alone or in combination with standard-dose tigecycline (TGC) in patients with non-bacteremic pneumonia due to XDR-Acb, and explored the factors influencing patients’ 30-day mortality. A 1:1 case (n = 106; receiving TGC plus AS-CMS) control (receiving AS-CMS alone with matching scores) observational study was conducted among adult patients with non-bacteremic XDR-Acb complex pneumonia in a Taiwanese medical center from January 2014 through December 2016. The clinically relevant data were retrospectively recorded. The primary endpoint was 30-day case fatality. Secondary endpoints investigated that if the co-morbidities, XDR-A. baumannii as a pneumonic pathogen, therapy-related factors, or airway colonization with colistin-resistant Acb negatively influenced the 14-day clinical condition of enrolled patients. A higher 30-day mortality rate was noted among the group receiving combination therapy (34.0% vs 22.6%; P = .17). The ≥7-day AS-CMS therapy successfully eradicated > 90% of airway XDR-Acb isolates. Nevertheless, follow-up sputum specimens from 10 (6.4% [10/156]) patients were colonized with colistin-resistant Acb isolates. After the conditional factors were adjusted by multivariate logistic analysis, the only factor independently predicting the 30-day case-fatality was the failure of treating XDR-Acb pneumonia at 14 days (adjusted odds ratio [aOR] = 38.2; 95% confidence interval [CI] = 9.96–142.29; P < .001). Cox proportional regression analysis found that chronic obstructive pulmonary disease (COPD) (adjusted hazard ratio [aHR] = 2.08; 95% CI = 1.05–4.10; P = .035), chronic renal failure (aHR = 3.00; 95% CI = 1.52–5.90; P = .002), non-invasive ventilation use (aHR = 2.68; 95% CI = 1.37–5.25; P = .004), and lack of TGC therapy (aHR = 0.52; 95% CI = 0.27–1.00; P = .049) adversely influenced the 14-day clinical outcomes. Conversely, the emergence of colistin-resistant Acb isolates in the follow-up sputum samples was not statistically significantly associated with curing or improving XDR-Acb pneumonia. In conclusion, aggressive pulmonary hygiene care, the addition of TGC, and corticosteroid dose tapering were beneficial in improving the 14-day patients’ outcomes.

To evaluate the susceptibility of globally pneumonia-causing meropenem-resistant (MEM-R) Acinetobacter baumannii isolates against important antibiotics and estimate appropriate dosages of indicated antibiotics. We extracted the 2014-2021 Antimicrobial Testing of Leadership Surveillance database regarding the susceptibility of MEM-R A. baumannii isolates causing pneumonia against important antibiotics. The susceptibility and carbapenemase-encoding gene (CPEG) data of pneumonia-causing MEM-R A. baumannii isolates from patients hospitalized in intensive care units of five major regions were analyzed. The susceptibility breakpoints (SBP) recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2022, other necessary criteria [SBP of MIC for colistin, 2 mg/L, in the CLSI 2018; and cefoperazone-sulbactam (CFP-SUL), 16 mg/L], and the pharmacokinetic and pharmacodynamic data of indicated antibiotics were employed. Applying the aforementioned criteria, we observed the susceptible rates of colistin, minocycline, and CFP-SUL against the pneumonia-causing MEM-R A. baumannii isolates globally (n=2,905) were 93.2%, 69.1%, and 26.3%, respectively. Minocycline was significantly more active in vitro (MIC ≤4 mg/L) against the pneumonia-causing MEM-R A. baumannii isolates collected from North and South America compared to those from other regions (>90% vs. 58-72%). Additionally, bla_OXA-23 and bla_OXA-72 were the predominant CPEG in pneumonia-causing MEM-R A. baumannii isolates. After deliberative estimations, dosages of 200 mg minocycline intravenously every 12 h (SBP, 8 mg/L), 100 mg tigecycline intravenously every 12 h (SBP, 1 mg/L), and 160 mg nebulized colistin methanesulfonate every 8 h (SBP, 2 mg/L) are needed for the effective treatment of pneumonia-causing MEM-R A. baumannii isolates.

Aztreonam-avibactam (ATM-AVI) and cefiderocol (CFDC) are two next-generation antibiotics that exhibit promising in vitro activity against metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE). However, differences in antibacterial spectra and resistance mechanisms among clinically important Gram-negative bacteria (GNB) between these two agents remain incompletely understood. English-language publications indexed in PubMed (1990-2026), records retrieved from Google Scholar, and the 2018-2024 Antimicrobial Testing Leadership and Surveillance database were extensively reviewed to assess their potential clinical utility. ATM-AVI demonstrates broad activity against KPC-, MBL-, and OXA-48/181-like-producing CRE. However, ATM-AVI non-susceptibility occurs in Escherichia coli and Providencia rettgeri isolates harboring bla_CMY, penicillin-binding protein 3 (PBP3) modifications, and porin dysfunction or acrA efflux overexpression. In contrast, CFDC activity is primarily compromised by NDM production, reduced expression of iron transporters, and PBP3 alterations. Significant regional variation in CFDC susceptibility among MBL-producing CRE isolates collected in Asia and North America/Europe has been observed. Based on limited pooled real-world treatment experience, CFDC shows moderate efficacy (73%) for the treatment of infections caused by MBL-producing CRE. Both antibiotics also show potential in vitro activity against ceftazidime-avibactam-resistant, non-carbapenemase-producing CRE. Notably, CFDC exhibits excellent in vitro activity against contemporary CR-Pseudomonas aeruginosa, most CR-Acinetobacter baumannii harboring bla_OXA-23/24/58 genes, Elizabethkingia anophelis, Stenotrophomonas maltophilia, Burkholderia cepacia, and Burkholderia pseudomallei. Nevertheless, CFDC heteroresistance is most prevalent among CR-A. baumannii isolates. Continued assessment of clinical treatment experience with these two antibiotics against MBL-producing CRE and important non-fermenting GNB is warranted to accumulate further evidence regarding their therapeutic roles.

Objectives. Acute respiratory distress syndrome (ARDS) is a critical complication in severe COVID-19 patients. The intravenous infusion (IVF) of umbilical cord- (UC-) mesenchymal stem cells (MSCs), validated to substantially reduce the release of several inflammatory cytokines in vivo, was also shown to exhibit benefits in improving hypoxemia among severe COVID-19 patients. A single dose of IVF-UC-MSCs therapy for severe COVID-19 patients was shown to alleviate the initial ARDS severity, but have 5067 case-fatality rates. In Taiwan, few adult patients with severe COVID-19-induced ARDS receiving compassionate adjuvant treatment consisting of either a single dose (11010⁶cells/kg body weight (kg BW)) or three doses (510⁶cells/kg BW in each dose) of IVF-UC-MSCs had good outcomes. However, the optimal dosage and rounds of IVF-UC-MSCs administration for the treatment of severe COVID-19 patients with ARDS are undetermined. Methods. We reviewed the 20202022 PubMed literature database concerning the clinical efficacy of IVF-UC-MSCs among severe COVID-19 patients. Results. The data of COVID-19 case series in the PubMed literature revealed a notable heterogeneity in the therapeutic dosage (a single dose: 11010⁶cells/kg BW; and three doses: 5020010⁶cells/kg BW in each dose) and the post-ARDS days of IVF-UC-MSCs administration (a single dose: 112; and multiple doses: 514) for the treatment of severe COVID-19-associated ARDS. The survival rates among these severe COVID-19 patients ranged from 50 to 76. However, an overall rate of 93.1 of significant improvement in hypoxemia was observed for the COVID-19 survivors receiving IVF-UC-MSCs at the initial ARDS stage. Conclusions. According to our analysis, the ideal treatment dosage of IVF-UC-MSCs for severe COVID-19-induced ARDS is likely 510⁶cells/kg BW for three cycles within 5 days of ARDS onset in severe COVID-19 patients.