Search Results (57)

Objective: The impact of a febrile neutropenia (FN) emergency department (ED) triage screening tool and protocol on time to antibiotic administration (TTA) and patient outcomes was evaluated. Methods: This was a retrospective, quasi-experimental study of adult FN patients admitted through the ED from April 2014 to April 2017. In March 2016 a triage screening tool and protocol were implemented. In patients who screened positive, nursing initiated a protocol that included laboratory diagnostics and a pharmacy consult for empiric antibiotics prior to evaluation by a provider. Patients were evaluated pre- and post-protocol for TTA, 30-day mortality, ED length of stay (LOS), and hospital LOS. Results: A total of 130 patients were included in the study, 77 pre-protocol and 53 post-protocol. Median TTA was longer in the pre-protocol group at 174 min (interquartile range [IQR] 105–224) vs. 109 min (IQR 71–214) post-protocol, p = 0.04. Thirty-day mortality was greater at 18.8% pre-protocol vs. 7.5% post-protocol, p = 0.12. There was no difference in hospital LOS. Pre-protocol patients compared to post-protocol patients who had a pharmacy consult demonstrated a further reduction in TTA (174 min [IQR 105–224] vs. 87.5 min [IQR 61.5–135], p < 0.01) and a reduced mortality (18% vs. 0%, p = 0.04). Conclusions: To our knowledge, this is the first report of a protocol for febrile neutropenia that allows pharmacists to order antibiotics based on a nurse triage assessment. Evaluation of the protocol demonstrated a significant reduction in TTA and trend toward improved mortality. Full article

Background: Aspiration pneumonia is increasingly recognized as a fatal pulmonary disease among older people. Although antipseudomonal antibiotics are commonly used in clinical practice, their efficacy in this population remains uncertain. Methods: Nationwide data collected from patients aged ≥65 years who were hospitalized due to aspiration pneumonia from January 2018 to December 2018 were analyzed. The in-hospital mortality between patients who received antipseudomonal antibiotics within 3 days of hospital admission and those who did not were compared. A logistic regression analysis was performed to assess the effect of antipseudomonal antibiotics on in-hospital mortality after adjusting for potential prognostic confounders. Results: This study included 46,980 patients, and 13,340 (28.4%) patients received antipseudomonal antibiotics. In total, 7011 (14.9%) patients died during hospitalization. Advanced age, male sex, a lower body mass index, decreased Barthel Index, impaired consciousness, interstitial pneumonia, malignancy, renal failure, and use of immunosuppressive agents were significantly associated with increased in-hospital mortality. After adjusting for the confounders, the use of antipseudomonal antibiotics was found to be associated with an elevated in-hospital mortality (odds ratio: 1.33; 95% confidence interval: 1.26–1.41; p < 0.001). Conclusions: In this nationwide data analysis of older patients with aspiration pneumonia, early antipseudomonal antibiotic administration did not improve prognosis. Therefore, the routine use of antipseudomonal antibiotics should be avoided in older patients with aspiration pneumonia. Full article

Background: Pseudomonas aeruginosa (PSA) infections are associated with a high recurrence rate and high mortality in immuno-compromised patients. There are limited studies regarding pediatric hematopoietic cell transplantation recipients. Aim: The nationwide multicenter study was conducted to analyze the epidemiology of PSA infections in children treated with chemotherapy (PHO, pediatric hematology and oncology) or undergoing hematopoietic allogeneic or autologous cell transplantation (HCT) in the period 2014–2023. Methods: We retrospectively analyzed the clinical and microbiological data of children who underwent anticancer therapy or hematopoietic cell transplantation in 17 Polish PHO centers and six pediatric HCT centers. The data were collected in two-year intervals. Results: During the 10-year study period, a total of 1629 HCTs (both autologous and allogeneic) and 9614 children newly diagnosed with neoplasms were analyzed. The cumulative incidence of PSA infection was similar in both groups (6.71% in PHO vs. 6.32% in HCT, p = 0.624). The total number of PSA bloodstream infections was comparable in the PHO and HCT groups (31.9% vs. 26.2%; p = 0.223). In both analyzed groups, the antipseudomonal drugs of choice were as follows: meropenem, ceftazidime, and tazobactam/piperaciline in combination with other antibiotics. In the HCT group, high rates of meropenem (20.4%) and tazobactam/piperaciline (18.4%) non-susceptibility were observed. This led to colistin therapy in 5.3% of patients. There was no difference in the median antibiotic therapy time in both groups; however, the survival rates from PSA infection were significantly lower in the HCT group (89.3% vs. 96.0%, p = 0.004). Conclusions: Although the risk of infection and the occurrence of resistant bacterial strains in HCT patients were comparable with those in PHO patients, the outcome of PSA infections was better in the PHO setting. Full article

Background/Objectives: Pseudomonas aeruginosa (Psa) can circumvent antimicrobial chemotherapy, an ability enhanced by cigarette smoking (CS). This study probed potential benefits of combinations of anti-pseudomonal agents, and potential augmentation by a macrolide, in the absence or presence of cigarette smoke condensate (CSC). Methods: Two susceptible (WT: wild-type and DS: drug-sensitive) and one multidrug-resistant (MDR) strains of Psa were treated with amikacin, cefepime, and ciprofloxacin, individually and in combination, and with and without clarithromycin, followed by the measurement of planktonic growth and biofilm formation by spectrophotometry. Antibiotic interactions were determined using the fractional inhibitory concentration index (FICI) method. Effects on preformed biofilm density were measured following the addition of antibiotics: all procedures were performed in the absence and presence of CSC. Results: The minimal inhibitory concentrations (MICs) of the three agents ranged from 0.125 mg/L to 1 mg/L (WT and DS strains) and 16 mg/L to 64 mg/L (MDR strain), with all resistant to clarithromycin (125 mg/L). MIC values closely correlated with the antibiotic concentrations required to inhibit biofilm formation. FICI revealed synergism between most combinations, with augmentation by clarithromycin. Amikacin had the greatest effect on biofilm density, which was potentiated by combination with the other antibiotics, particularly clarithromycin. Exposure to CSC had variable, albeit modest, effects on bacterial growth and biofilm formation, but low concentrations increased biofilm mass and attenuated synergistic antimicrobial interactions and effects on biofilm density. Conclusions: Amikacin, cefepime, and ciprofloxacin, especially with clarithromycin, exhibit synergistic anti-pseudomonal activity and decrease preformed biofilm density. CSC attenuated these effects, illustrating the pro-infective potential of CS. Full article

Background/Objectives: Although chronic infection by Pseudomonas aeruginosa among patients with bronchiectasis is associated with poor prognosis, the impact of antibiotics with P. aeruginosa coverage in patients with bronchiectasis who experienced bacterial pneumonia or exacerbation of bronchiectasis has not been fully investigated. Methods: This study targeted patients with bronchiectasis who were admitted to hospitals because of bacterial pneumonia or exacerbation of bronchiectasis between April 2018 and March 2020 using a national inpatient database in Japan. The association of antipseudomonal antibiotic treatment with in-hospital mortality was assessed after propensity score matching to adjust the patients’ backgrounds. Results: In total, 4943 patients with bacterial pneumonia and 1914 patients with exacerbation of bronchiectasis were included in this study. The in-hospital mortality rate did not differ between patients who did and did not receive antipseudomonal agents among patients with bacterial pneumonia (9.0% [185/2045] vs. 7.4% [151/2045]; p = 0.053) and those with exacerbation of bronchiectasis (5.2% [42/803] vs. 4.1% [33/803] group; p = 0.287). Conclusions: The use of antibiotics covering P. aeruginosa does not apparently improve prognosis in patients with bacterial pneumonia or exacerbation of bronchiectasis. A prospective study focusing on the impact of antibiotics covering P. aeruginosa among patients with bronchiectasis in whom P. aeruginosa is isolated is required. Full article

Background. Pseudomonas aeruginosa is one of the major concerns among bacterial diseases even when it shows a wild-type susceptibility pattern. In 2020, EUCAST reconsidered antibiogram interpretation shifting “I” from “intermediate” to “sensible, increased exposure” with possible significant impact on antibiotic prescription. The aim of this study was to evaluate mortality in patients with P. aeruginosa bloodstream infections treated with antipseudomonal penicillins or cephalosporins vs. carbapenems and ceftazidime/avibactam. Methods. This is a retrospective observational study. All the patients with a bloodstream infection due to P. aeruginosa admitted to our hospital were enrolled. Exclusion criteria were as follows: extremely critical conditions, age <18 years, pregnancy, isolation of a strain non-susceptible to piperacillin/tazobactam and antipseudomonal cephalosporins. Patients were divided into group A (treatment with carbapenems or ceftazidime/tazobactam) and group B (treatment with antipseudomonal penicillin or cephalosporins). Results. We enrolled 77 patients, 56 and 21 in groups A and B, respectively. The two groups were homogeneous for age, sex, and biochemical and clinical characteristics at admission. All-cause in-hospital mortality was 17/56 (30.4%) and 3/21 (14.3%) in groups A and B, respectively (p > 0.1). In group A, in-hospital BSI-related mortality was 23.2% (13/56), while it was 14.3% (3/21) in group B (p > 0.1). After multivariate analysis, only the PITT score represented a risk factor for BSI-related mortality (OR 2.917, 95% CI 1.381–6.163). Conclusions. Both all-cause and BSI-related mortality were comparable between the two groups. Treatment with carbapenem or ceftazidime/avibactam did not represent a protective factor for mortality in wild-type P. aeruginosa BSI. Full article

Antibiotic resistance is a critical public health issue. Among the multi-drug resistant microorganisms in question, Pseudomonas aeruginosa has been designated by the WHO as a priority threat. Its virulence is orchestrated through quorum sensing (QS). This sophisticated communication network relies on the release and perception of autoinducers acting as population density indicators. Therefore, the interest of a quorum silencing pharmacological approach has unfolded to quench bacterial pathogenicity without impairing growth. In this article, we reported the development of a family of indazole–quinolone hybrids as anti-virulence agents. These new biaromatic compounds were designed as potential specific QS quenchers against P. aeruginosa. Our transdisciplinary research methodology included their synthesis using palladocatalyzed cross-coupling reactions, as well as their in silico physicochemical and in vitro biological evaluation. The hit 7-chloro-2-indazolyl-4-quinolone Ie shows a promising anti-biofilm and anti-pyocyanin efficiency (35% inhibition at 25 µM and 35% inhibition at 100 µM, respectively) without an anti-pseudomonal bacteriostatic effect. It also demonstrated a moderate eukaryotic cytotoxicity. Its anti-QS properties have been investigated using metabolomic and molecular modelling studies. Full article

Diabetes prevalence continues to increase worldwide, which has led to a rising incidence of diabetes-related foot infections (DFIs). There is significant local variation in the microbiology of DFIs, and Pseudomonas spp. is suggested to be more prevalent in subtropical climates. The aim of this study was to investigate the local microbiological findings in patients admitted to the hospital with DFIs. This retrospective study analysed data from all adult patients diagnosed with diabetes and admitted to the hospital for the treatment of a DFI between 1 January 2021 and 31 December 2022. Both superficial wound swabs and tissue cultures were included. The Infectious Diseases Society of America classification system was used to categorise the severity of the DFI. Patient characteristics and demographics were analysed using descriptive statistics. One hundred fifty-one episodes of care were included. Most of the DFIs were classified as moderate infections 101/151 (67%). The most commonly isolated microorganism was Staphylococcus aureus (33%) followed by normal skin flora (11%) and β-haemolytic streptococci (7%). P. aeruginosa was isolated more commonly in those with chronic DFIs (10%) compared to those with acute DFIs (2%). Despite the frequent identification of S. aureus, 83% of patients received an antipseudomonal antibiotic. The introduction of multidisciplinary DFI rounds should be considered. Full article

Background: Due to its rapid resistance development and ability to form biofilms, treatment of Pseudomonas aeruginosa infections is becoming more complicated by the day. Drug combinations may help reduce both resistance and biofilm formation. Methods: Using the microtiter plate assay, we investigated the in vitro inhibition of biofilm formation and the disruption of preformed biofilms in multidrug-resistant and extensively drug-resistant clinical isolates of P. aeruginosa in the presence of peak plasma levels of eight antipseudomonal antibiotics alone and in combination with fosfomycin: ceftazidime, piperacillin/tazobactam, cefepime, imipenem, gentamicin, amikacin, ciprofloxacin and colistin. Results: Combination therapy was significantly superior to monotherapy in its inhibition of biofilm formation. The highest inhibition rates were observed for combinations with colistin, cefepime and ceftazidime. Conclusion: Our results support fosfomycin combination therapy as an enhanced prophylactic option. Moreover, combinations with β-lactam antibiotics and colistin demonstrated a more potent inhibition effect on biofilm formation than protein synthesis inhibitors. Full article

Purpose: Although the international guidelines for managing bronchiectasis are centred on preventing the exacerbation of bronchiectasis, the medical causes of admissions to hospital among patients with bronchiectasis have not been fully investigated. Methods: This study targeted patients with bronchiectasis who were admitted to hospitals between April 2018 and March 2020 using the national inpatient database in Japan. The causes of hospitalisation and types of antibiotics used for hospitalised patients were recorded. Results: In total, 21,300 hospitalisations of 16,723 patients with bronchiectasis were analysed. The most common cause was respiratory diseases in 15,145 (71.1%) admissions, including bacterial pneumonia and the exacerbation of bronchiectasis in 6238 (41.2%) and 3151 (20.8%), respectively. Antipseudomonal antibiotics were used in approximately 60% of patients with bacterial pneumonia who were administered antibiotic treatments and in approximately 50% of patients with the exacerbation of bronchiectasis. Conclusions: Bacterial pneumonia was the most frequent cause of hospitalisation, followed by the exacerbation of bronchiectasis, among patients with bronchiectasis. Physicians need to focus on the prevention of bacterial pneumonia in addition to the exacerbation of bronchiectasis in patients with bronchiectasis. Full article

Evidence on the optimal antibiotic strategy for empyema is lacking. Our database study aimed to evaluate the effectiveness of empirical anti-pseudomonal antibiotics in patients with empyema. We utilised a Japanese real-world data database, focusing on patients aged ≥40 diagnosed with empyema, who underwent thoracostomy and received intravenous antibiotics either upon admission or the following day. Patients administered intravenous vasopressors were excluded. We compared thoracic surgery and death within 90 days after admission between patients treated with empirical anti-pseudomonal and non-anti-pseudomonal antibiotics. Cause-specific hazard ratios for thoracic surgery and death were estimated using Cox proportional hazards models, with adjustment for clinically important confounders. Subgroup analyses entailed the same procedures for patients exhibiting at least one risk factor for multidrug-resistant organisms. Between March 2014 and March 2023, 855 patients with empyema meeting the inclusion criteria were enrolled. Among them, 271 (31.7%) patients received anti-pseudomonal antibiotics. The Cox proportional hazards models indicated that compared to empirical non-anti-pseudomonal antibiotics, empirical anti-pseudomonal antibiotics were associated with higher HRs for thoracic surgery and death within 90 days, respectively. Thus, regardless of the risks of multidrug-resistant organisms, empirical anti-pseudomonal antibiotics did not extend the time to thoracic surgery or death within 90 days. Full article

Outpatient parenteral antimicrobial therapy (OPAT) is a useful treatment strategy against Pseudomonas aeruginosa and other multidrug-resistant bacteria. However, it is hindered by the lack of stability data for the administration of antibiotics under OPAT conditions. Our objective was to investigate the stability of nine antipseudomonal and broad-spectrum beta lactam antibiotics (aztreonam, cefepime, cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, meropenem/vaborbactam, and piperacillin/tazobactam) to allow the spread of OPAT programs. All the antibiotics were diluted in 500 mL 0.9% sodium chloride and stored at 4, 25, 32, and 37 °C for 72 h in two different devices (infusion bags and elastomeric pumps). The solutions were considered stable if the color, clearness, and pH remained unchanged and if the percentage of intact drug was ≥90%. All the antimicrobials remained stable 72 h under refrigerated conditions and at least 30 h at 25 °C. At 32 °C, all the antibiotics except for meropenem and meropenem/vaborbactam remained stable for 24 h or more. At 37 °C, only aztreonam, piperacillin/tazobactam, cefepime, cefiderocol, and ceftolozane/tazobactam were stable for at least 24 h. The stability results were the same in the two devices tested. All the antibiotics studied are actual alternatives for the treatment of antipseudomonal or multidrug-resistant infections in OPAT programs, although the temperature of the devices is crucial to ensure antibiotic stability. Full article

Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium renowned for its resilience and adaptability across diverse environments, including clinical settings, where it emerges as a formidable pathogen. Notorious for causing nosocomial infections, P. aeruginosa presents a significant challenge due to its intrinsic and acquired resistance mechanisms. This comprehensive review aims to delve into the intricate resistance mechanisms employed by P. aeruginosa and to discern how these mechanisms can be inferred by analyzing sensitivity patterns displayed in antibiograms, emphasizing the complexities encountered in clinical management. Traditional monotherapies are increasingly overshadowed by the emergence of multidrug-resistant strains, necessitating a paradigm shift towards innovative combination therapies and the exploration of novel antibiotics. The review accentuates the critical role of accurate antibiogram interpretation in guiding judicious antibiotic use, optimizing therapeutic outcomes, and mitigating the propagation of antibiotic resistance. Misinterpretations, it cautions, can inadvertently foster resistance, jeopardizing patient health and amplifying global antibiotic resistance challenges. This paper advocates for enhanced clinician proficiency in interpreting antibiograms, facilitating informed and strategic antibiotic deployment, thereby improving patient prognosis and contributing to global antibiotic stewardship efforts. Full article

Hospital-acquired infections caused by P. aeruginosa contribute to global distress because of the elevated rates of microbial antibiotic resistance. Aminoglycosides are antipseudomonal agents that are effectively and frequently utilized to eradicate this infection. This current study is a retrospective study investigating plasmid-mediated aminoglycoside resistance by focusing on the prevalence of the genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methylase among P. aeruginosa clinical isolates from Taif, Saudi Arabia. A hundred clinical isolates of P. aeruginosa were collected. The isolates were identified from February 2021 to February 2022. Antibiotic susceptibility testing and MICs were determined using (DD) and (BM-MIC) testing, respectively. AMEs and 16S rRNA methylase variants in bacterial isolates were amplified via PCR for genetic detection. A relatively high multiple antibiotic resistance rate corresponding to 10–32% was reported. Eighteen percent of P. aeruginosa isolates were gentamicin–amikacin–tobramycin resistant according to the MIC levels. The aminoglycoside-resistant strains were additionally identified via GyrA gene sequencing. The phylogenic relatedness dendrogram of the sequenced GyrA genes was performed using a neighbor-joining method via MEGAX software version 10.2.6. The most prevalent AME encoding gene was aac(6′)-Ib, observed in 94.4% of resistant isolates, while a resistance gene cocktail of [aac(6′)-Ib and ant(3″)-I] was a highly frequent combination (27.8%). This study updated the knowledge about aminoglycoside resistance mechanisms in P. aeruginosa, which constitutes an urgent need, especially after the COVID-19 crisis, which was associated with increased antimicrobial use and resistance rates. Full article

Pseudomonas aeruginosa (P. aeruginosa) poses a grave clinical challenge due to its multidrug resistance (MDR) phenotype, leading to severe and life-threatening infections. This bacterium exhibits both intrinsic resistance to various antipseudomonal agents and acquired resistance against nearly all available antibiotics, contributing to its MDR phenotype. Multiple mechanisms, including enzyme production, loss of outer membrane proteins, target mutations, and multidrug efflux systems, contribute to its antimicrobial resistance. The clinical importance of addressing MDR in P. aeruginosa is paramount, and one pivotal determinant is the resistance-nodulation-division (RND) family of drug/proton antiporters, notably the Mex efflux pumps. These pumps function as crucial defenders, reinforcing the emergence of extensively drug-resistant (XDR) and pandrug-resistant (PDR) strains, which underscores the urgency of the situation. Overcoming this challenge necessitates the exploration and development of potent efflux pump inhibitors (EPIs) to restore the efficacy of existing antipseudomonal drugs. By effectively countering or bypassing efflux activities, EPIs hold tremendous potential for restoring the antibacterial activity against P. aeruginosa and other Gram-negative pathogens. This review focuses on concurrent MDR, highlighting the clinical significance of efflux pumps, particularly the Mex efflux pumps, in driving MDR. It explores promising EPIs and delves into the structural characteristics of the MexB subunit and its substrate binding sites. Full article