UNASSIGNED: Extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) is a growing concern due to its increasing incidence, limited therapeutic options, limited data on the optimal treatment, and high mortality rates. The study aimed to characterize the population, the outcome and the microbiological characteristics of XDR-PA identified in a Portuguese university hospital center.
UNASSIGNED: All XDR-PA isolates between January 2019 and December 2021 were identified. XDR-PA was defined as resistance to piperacillin-tazobactam, third and fourth generation cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. A retrospective analysis of the medical records was performed.
UNASSIGNED: One hundred seventy-eight individual episodes among 130 patients with XDR-PA detection were identified. The most common sources of infection were respiratory (32%) and urinary tracts (30%), although skin and soft tissue infections (18%) and primary bacteremia (14%) were also prevalent. Colonization was admitted in 64 cases. Several patients had risk factors for complicated infections, most notably immunosuppression, structural lung abnormalities, major surgery, hemodialysis or foreign intravascular or urinary devices. XDR-PA identification was more frequent in male patients with an average age of 64.3 ± 17.5 years. One non-susceptibility to colistin was reported. Only 12.4% were susceptible to aztreonam. Ceftazidime-avibactam (CZA) was susceptible in 71.5% of the tested isolates. Ceftolozane-tazobactam (C/T) was susceptible in 77.5% of the tested isolates. Antibiotic regimens with XDR-PA coverage were reserved for patients with declared infection, except to cystic fibrosis. The most frequently administered antibiotics were colistin (41 cases), CZA (39 cases), and C/T (16 cases). When combination therapy was used, CZA plus colistin was preferred. The global mortality rate among infected patients was 35.1%, significantly higher in those with hematologic malignancy (50.0%, p < 0.05), followed by the ones with bacteremia (44.4%, p < 0.05) and those medicated with colistin (39.0%, p < 0.05), especially the ones with respiratory infections (60.0%). Among patients treated with CZA or C/T, the mortality rate seemed to be lower.
UNASSIGNED: XDR-PA infections can be severe and difficult to treat, with a high mortality rate. Even though colistin seems to be a viable option, it is likely less safe and efficient than CZA and C/T. To the best of the authors\' knowledge, this is the first description of the clinical infection characteristics and treatment of XDR-PA in Portugal.

UNASSIGNED: To determine the clinical features, outcomes, and factors associated with the emergence of colistin-resistant gram-negative rods isolated from patients admitted to intensive care units.
UNASSIGNED: This cross-sectional study was conducted at the intensive care units of Liaquat National Hospital, from April 2019 to February 2020. Gram-negative rods resistant to colistin with minimum inhibitory concentrations ⩾ 4 mcg/mL according to Clinical and Laboratory Standards Institute criteria as reported in cultures were included. Clinical, demographical data and treatment given were recorded and analyzed using SPSS version 25.
UNASSIGNED: A total of 93 patients were included; 58.1% were males. The mean age of patients was 59.48 ± 18.36 years. The most common organism isolated was Klebsiella pneumoniae (91.4%). The most common specimen was the tracheal (62.4%). Ventilator-acquired pneumonia was seen in 38.7%. The most common co-morbid disease seen in patients was diabetes (41%); 77% had a symptomatic infection and were treated with a combination of 2 or more antibiotics, most commonly meropenem plus fosfomycin. The most common susceptible antibiotics were fosfomycin (72%) and tigecycline (50.5%). Mean intensive care unit stay and total duration of hospital stay were prolonged (16.83 ± 12.93 and 23.34 ± 17.52 days, respectively). Forty-eight (62.3%) patients with symptomatic infection with colistin-resistant isolates were treated and discharged, and mortality was seen in 23 (29.9%). A significant association was found between mortality and symptomatic infection, endotracheal intubation with mechanical ventilation (p = 0.003), and a prolonged hospital stay of >20 days (p = 0.041).
UNASSIGNED: Colistin-resistant gram-negative rods pose a significant problem especially in developing countries because of limited therapeutic options. Stringent infection control and comprehensive antimicrobial stewardship programs are needed to overcome this challenge.

UNASSIGNED: Extensively drug-resistant Acinetobacter baumannii (XDR-AB) infections have become difficult to treat and are associated with a high mortality rate. Tigecycline is one of the most effective agents used to treat XDR-AB infections, but data from treating bloodstream infection (BSI) in standard dose do not look promising, because of its low plasma concentration. Secondary BSI with primary infection source may indicate tigecycline treatment with a higher dose. Currently, little is known about the application of high-dose tigecycline among patients with secondary BSI caused by XDR-AB. We aimed to investigate the outcomes for high-dose (HD) tigecycline treatment versus standard-dose (SD) treatment of these patients.
UNASSIGNED: An observational cohort study was conducted at four university affiliated hospitals in mainland China. Adult inpatients who were confirmed as having secondary BSI caused by XDR-AB and received definitive tigecycline treatment were consecutively included. Patients who were treated with 50 mg every 12 h were defined as the SD group, and a twice dose was defined as the HD group.
UNASSIGNED: Of the enrolled patients, 63 received SD and 88 received HD tigecycline treatment. Patients in the two groups had similar with regard to baseline clinical conditions. The 30-day survival was affected by the source of the primary infection. Survival was significantly better in patients with non-pulmonary-infection-related BSI than in patients with pulmonary-infection-related BSI. Multivariate Cox regression confirmed that HD had a protective effect only observed in patients with non-pneumonia-related BSI.
UNASSIGNED: A tigecycline dose that is twice its standard dose is better for the treatment of XDR-AB infection only in BSI associated with non-pulmonary infection.

BACKGROUND: The lack of accurate and efficient diagnostic devices for extensively drug-resistant tuberculosis (XDR-TB) makes it a severe threat to global public health. A prospective clinical study in an intended-use cohort was designed to evaluate the Akonni Biosystems XDR-TB TruArray and lateral flow cell (XDR-LFC) to address this gap in tuberculosis diagnostics.
OBJECTIVE: This paper presents the protocol for a study that aims to document the conceptualization and design of this evaluation method for early dissemination while data collection and analysis are ongoing.
METHODS: The clinical study was conducted in three phases. The first phase was to observe changes in bacterial load and culture positivity in patient sputa over time and better understand the diversity of prospective clinical samples. The second phase was to prospectively collect clinical samples for sensitivity and specificity testing of the Akonni Biosystems XDR-LFC device. Lastly, the third phase was to explore the anti-TB drug concentrations in serum throughout the drug-resistant tuberculosis treatment.
RESULTS: The methodology described includes the study design, laboratory sample handling, data collection, and the protection elements of human subjects of this clinical study to evaluate a potential new XDR-TB diagnostic device. A total of 664 participants were enrolled across the three phases. The implemented complex systems facilitated a thorough clinical data collection for an objective evaluation of the device. The study is closed to recruitment. The follow-up data collection and analysis are in progress.
CONCLUSIONS: This paper outlined a prospective cohort study protocol to evaluate a rapid XDR-TB detection device, which may be informative for other researchers with similar goals.
UNASSIGNED: DERR1-10.2196/26748.

Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip and knee PJIs diagnosed at a Brazilian tertiary hospital from January 2014 to July 2018. RFs associated with MDR-GNB PJI were estimated by bivariate and multivariate analyses using prevalence ratios (PRs) with significance at p < 0.05. Kaplan-Meier analysis was performed to evaluate treatment outcomes. Overall, 98 PJI patients were analysed, including 56 with MDR-GNB and 42 with other bacteria. Independent RFs associated with MDR-GNB PJI were revision arthroplasty (p = 0.002), postoperative hematoma (p < 0.001), previous orthopaedic infection (p = 0.002) and early infection (p = 0.001). Extensively drug-resistant GNB (p = 0.044) and comorbidities (p = 0.044) were independently associated with MDR-GNB PJI treatment failure. In sum, MDR-GNB PJI was independently associated with previous orthopaedic surgery, postoperative local complications and pre-existing infections and was possibly related to selective pressure on bacterial skin colonisation by antibiotics prescribed for early PJI. Infections due to MDR-GNB and comorbidities were associated with higher treatment failure rates.

Bacteria resistant to different classes of antimicrobial agents are a major threat to humanity and risk leading the world towards the return of the pre-antimicrobial era. This study was undertaken to detect the incidence of extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria in a tertiary-care hospital in Bhubaneswar, Odisha, India.
Positive bacterial cultures from different clinical samples were identified using a VITEK®2 compact system and the antimicrobial susceptibility profile of different Gram-negative bacteria was analysed.
A total of 2489 clinical samples were collected and processed for culture during the period January 2013 to April 2017. Of 1103 pure bacterial cultures, 690 (62.6%) were Gram-negative bacteria. The antimicrobial susceptibility profile of Gram-negative bacterial strains revealed that 41.3% (n=285) were XDR and 8.1% (n=56) were PDR. Rates of colistin and tigecycline resistance were 16% and 51.9%, respectively.
This situation demands regular surveillance of antimicrobial resistance of Gram-negative bacteria and implementation of an efficient infection control programme.