Antipseudomonal Agents Research Articles

Evaluation of risk factors for 14-day and 30-day mortality among treatment regimens against Pseudomonas aeruginosa resistant to carbapenem but susceptible to traditional antipseudomonal non-carbapenem β-lactam agents.

Pseudomonas aeruginosa associated with hospital-acquired infection is often resistant to various antibiotics and is associated with high mortality worldwide. The appropriate treatment of Pseudomonas aeruginosa resistant to carbapenems but susceptible to traditional antipseudomonal non-carbapenem β-lactam agents (Car-R/NonCar-S P. aeruginosa) remains unclear. This retrospective study evaluated risk factors for 14-day and 30-day mortality among treatment regimens against Car-R/NonCar-S P. aeruginosa. This study enrolled 180 patients with Car-R/NonCar-S P. aeruginosa infection at Phramongkutklao Hospital between January 2019 and December 2023. The 14-day and 30-day mortality rates were 18.3% and 28.9%, respectively. Bloodstream infection (OR 1.97, 95% CI 0.88-4.43), septic shock (OR 3.3, 95% CI 1.30-8.40), Acute Physiology and Chronic Health Evaluation (APACHE) II < 14 (OR 0.13, 95% CI 0.03-0.54), Sequential Organ Failure Assessment (SOFA) <7 (OR 0.25, 95% CI 0.11-0.56), and Pitt bacteremia score <4 (OR 0.16, 95% CI 0.05-0.47) were associated with 14-day mortality. There was a higher 14-day and 30-day mortality in patients treated with piperacillin/tazobactam or aminoglycosides but there was no significant difference among antipseudomonal antimicrobial agents in the treatment of Car-R/NonCar-S P. aeruginosa infection. We supported the use of traditional antipseudomonal β-lactam agents to treat Car-R/NonCar-S P. aeruginosa infections, however the use of piperacillin/tazobactam might be concerned in some cases and further investigations were needed.

Trends and implications of antimicrobial resistance in Pseudomonas aeruginosa: Insights from a 19-year study in Zhejiang Province.

This study aimed to elucidate the resistance trends of P. aeruginosa isolates from 2005 to 2023 in Zhejiang Province, emphasizing the impact of Coronavirus disease 2019 (COVID-19) on antimicrobial resistance patterns and clinical management. We retrospectively analyzed 7326 P. aeruginosa isolates collected from diverse clinical sources in a tertiary hospital in Zhejiang Province from 2005 to 2023. Identification and antibiotic susceptibility testing of each isolate were performed using the VITEK-32 automated system and the disk diffusion method, following Clinical and Laboratory Standards Institute guidelines. We assessed resistance patterns for key antibiotic classes relevant to P. aeruginosa treatment, including carbapenems, β-lactams, aminoglycosides, and quinolones. Statistical analyses, including trend evaluations and resistance determinant assessments, were conducted in R software (version 4.2.2), with visualizations generated through ggplot2 to illustrate resistance trends over time. This study focused on key anti-pseudomonal agents including carbapenems (imipenem and meropenem), β-lactams (piperacillin), and quinolones (ciprofloxacin and levofloxacin). We observed a progressive increase in resistance to imipenem from 6.8% in 2005 to 48.2% in 2023 and meropenem from 25.4% to 44.2% over the same period. Conversely, resistance rates to aminoglycosides declined, with gentamicin resistance dropping from 22.0% in 2005 to 5.0% in 2019. Cephalosporins exhibited variable trends, with cefepime resistance peaking at 40.4% in 2013 before declining to 12.1% in 2023. The findings indicated a progressive increase in resistance rates for these antibiotics, with notable peaks coinciding with changes in clinical practices and the COVID-19 pandemic. The analysis demonstrated that shifts in prescription habits, particularly during the COVID-19 pandemic, influenced resistance patterns, underscoring the need for context-specific antimicrobial stewardship strategies. This study identifies significant, evolving resistance patterns in P. aeruginosa over a 19-year period, with marked increases in resistance to critical antibiotics, including carbapenems (imipenem, meropenem), quinolones (levofloxacin, ciprofloxacin), and certain β-lactams (piperacillin). These findings underscore an urgent need for dynamic, tailored infection control measures, emphasizing the importance of robust antibiotic stewardship programs, localized treatment guidelines, and proactive monitoring of resistance trends. Implementing these strategies is essential to effectively counter the challenges posed by multi-drug resistant P. aeruginosa, improve patient outcomes, and sustain the efficacy of vital antibiotic therapies.

BlaGES-producing ST654 comprises a quarter of all carbapenem-resistant Pseudomonas aeruginosa in blood isolates from 15 hospitals.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) are of major clinical concern. We analyzed 85 P. aeruginosa blood isolates non-susceptible to carbapenems collected during 2021-2023 from 15 medical centers in Israel. We aimed to determine the prevalence of high-risk clones, examine clonality, test antibiotic susceptibility, and assess the presence of acquired resistance genes, including carbapenemases. Whole-genome sequencing was performed using Illumina sequencing technology. Susceptibly was determined using the broth microdilution method. In the entire sample, 43.5% were high-risk clones. A main clade (27.1% of isolates) found in multiple hospitals comprised 19 isolates belonging to the high-risk ST654 clone and four closely related isolates. The isolates in this main clade harbored a broad set of resistance genes, including GES-type genes, and 91% had a mutated outer membrane protein (OprD). Isolates in the main clade were uniformly tobramycin (TOB) resistant and 83% were ceftolozane/tazobactam resistant. In the entire sample, we found high resistance to most antipseudomonal agents, including new beta-lactam/beta-lactamase inhibitor combinations. No uniform susceptibility to an antipseudomonal agent was found. Carbapenemases were carried by 9.4% of isolates (5.9% blaGES-5 and 3.5% blaNDM-1) and oprD was mutated in 67% of isolates. Thus, the epidemiology of CRPA is explained by a combination of clonal expansion of a dominant high-risk clade and sporadic occurrence of mutated strains. Our findings highlight the importance of susceptibility testing using a wide panel of antibiotics when CRPA is detected. Prevention measures tracking and controlling emerging high-risk clades and clones are crucial to limit the spread of CRPA.

Alpinia officinarum Hance Essential Oil as Potent Antipseudomonal Agent: Chemical Profile, Antibacterial Activity, and Computational Study.

Alpinia officinarum Hance, is an aromatic and medicinal herb with a very interesting history and prominent chemical and biological prospects. We aimed to investigate the antibacterial activity of Alpinia officinarum essential oil and the preferred molecular targets of its constituents together with their pharmacokinetic properties and toxicity profile. According to GC-MS analysis, eucalyptol was the main compound (27.52 %) identified in Alpinia officinarum essential oil, followed by α-terpineol, and β-sesquiphellandrene. As opposed to the weak antiradical activity estimated by DPPH and ABTS tests, the essential oil caused inhibition of all the bacteria following well-diffusion and microdilution methods, especially the gram-negative Pseudomonas aeruginosa and Escherichia coli. It displayed exceptionally remarkable activity against Pseudomonas aeruginosa by totally inhibiting its growth on the agar plate exceeding the effect of chloramphenicol standard. This bactericidal effect was confirmed by very low MIC and MBC values of 0.82 and 6.562 μg/mL, respectively. The molecular docking showed interesting binding affinity between the major compounds and various drug targets in Pseudomonas aeruginosa, also good pharmacokinetic and toxicity behavior. These encouraging findings are particularly relevant in light of the increasingly pressing challenge to find alternative substances with antibacterial aptitude to address the issue of antibiotic resistance among infectious bacteria.

Not all carbapenem-resistant Pseudomonas aeruginosa strains are alike: tailoring antibiotic therapy based on resistance mechanisms.

To correlate the resistance mechanisms and the susceptibility to new antibiotics in Pseudomonas aeruginosa . Definition of antibiotic resistance in Pseudomonas aeruginosa is still debated. Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) are used but which of them better correlate with the risk of mortality remains debated. Mechanisms underlying resistance in Pseudomonas aeruginosa are complex and may be combined, resulting in unpredictable phenotype and cross-resistance. Thus, not all CRPA are alike and tailoring antibiotic therapy on resistance mechanisms is challenging. Current guidelines recommend the use of new antipseudomonal agents for CRPA or DTR-PA infections but they don't provide specific information on how tailoring antibiotic therapy on underlying resistance mechanisms. This review may be useful to understand which mechanisms are involved in CRPA and may have practical implications helping clinicians to select an appropriate antibiotic regimen. Several antibiotics are now available for Pseudomonas aeruginosa but their rational use is important to avoid development of future resistance. The knowledge of local epidemiology and most common resistance mechanisms may guide empirical therapy, but targeted antibiotic therapy should be re-evaluated as soon as susceptibility testing profile is available and selected according to Pseudomonas aeruginosa phenotype.

The Changes in Broad-spectrum Antimicrobial Consumption during the COVID-19 Pandemic in a Japanese Acute Tertiary-care Hospital: An Interrupted Time-series Analysis.

Objective The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and hospitals in Japan have been forced to respond to the situation. This study evaluated the broad-spectrum antimicrobial use before and during the COVID-19 pandemic in an acute tertiary-care hospital. Methods This single-center, retrospective study was conducted between January 2019 and June 2021. Patients We reviewed patients treated with three broad-spectrum antipseudomonal agents: carbapenems, tazobactam/piperacillin, and cefepime. Monthly aggregated hospital antimicrobial consumption was measured as days of therapy (DOTs) per 1,000 patient-days, and the monthly incidences of Clostridioides difficile infection (CDI), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenemase-producing Enterobacteriaceae (CPE) were recorded. Results The median monthly carbapenem-DOTs during the pre-pandemic and pandemic era were 8.4 and 8.2 per 1,000 patient-days, respectively. A time-series analysis showed non-significant changes in the level between periods (coefficients: 2.08; 95% confidence interval [CI]: -2.9 to 7.0; p=0.44). No change in the trend of monthly carbapenem-DOTs was observed after intervention. No post-intervention changes in the incidence of MRPA or CPE were observed; however, the trend in the incidence of CDI per 1,000 patient-days significantly differed between the two periods (coefficient: -0.04; 95% CI: -0.07, 0.00; p=0.01), and a downward trend was observed in the monthly CDI incidence during the COVID-19 period. Conclusion The consumption of broad intravenous antimicrobial agents has not changed significantly during the pandemic. We need to maintain the quality of medical care, including antimicrobial stewardship, even in specialized resource-limited facilities during a pandemic.

Biogenically synthesized porous TiO2 nanostructures for advanced anti-bacterial, electrochemical, and photocatalytic applications

This study develops environmentally benign capping technique to synthesize nanoparticles of Curcuma longa-coated titanium dioxide (CR-TiO2) from titanium isopropoxide by utilizing the extract of Rosa rubiginosa flowers as reducing and chelating agent. The biogenically synthesized nanoparticles revealed excellent anti-bacterial, electrochemical, and photocatalytic properties due to the presence of porous TiO2 nanostructures. The sharp peaks by XRD pattern showed the crystallinity and phase purity of TiO2 nanoparticles. BET analysis proved mesoporous nature of the materials with specific surface area of 134 m2 g −1. The vibrational spectra suggest hydroxyl groups from flavonoids of Curcuma longa acting as functionalizing agent for TiO2 nanoporous structures with visible luminescence, which is proven in fluorescence spectra and is applicable for photocatalytic studies. The anti-bacterial studies showed good inference on TiO2 nanoparticles against Pseudomonas auruginosa and proved it to be an excellent antipseudomonal agent with the oxidative potential. The maximum degradation of phenol red dye in the presence of TiO2 under visible light conditions was observed. The supercapacitor fabricated using the biogenic TiO2 three-electrode system exhibited a specific capacitance of 128 Fg-1 (10 mV s−1), suggesting it as an excellent electrode material. The LSV curve at 50 mV s−1 scan rate showed that oxygen reduction potential (ORR) of CR-TiO2 electrodes was 121 mV. The present study is a new application of nanoparticles in sustainability consideration of the environment as well as a solution to the power crisis with fewer limitations. The well-distinguished antidiabetic and BSA denaturation potential suggests that these porous TiO2 nanostructures can be useful for drug delivery as glucose inhibitors and oral anti-inflammatory drugs with the restriction of adverse side effects.

Trends in Empiric Broad-Spectrum Antibiotic Use for Suspected Community-Onset Sepsis in US Hospitals

Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time. To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis. This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission. Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal β-lactam agent use. Annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of β-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics. Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal β-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal β-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13). In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.

Evaluation of fortimicin antibiotic combinations against MDR Pseudomonas aeruginosa and resistome analysis of a whole genome sequenced pan-drug resistant isolate

BackgroundMultidrug-resistant (MDR) P. aeruginosa is a rising public health concern, challenging the treatment of such a ubiquitous pathogen with monotherapeutic anti-pseudomonal agents. Worryingly, its genome plasticity contributes to the emergence of P. aeruginosa expressing different resistant phenotypes and is now responsible for notable epidemics within hospital settings. Considering this, we aimed to evaluate the synergistic combination of fortimicin with other traditional anti-pseudomonal agents and to analyze the resistome of pan-drug resistant (PDR) isolate.MethodsStandard methods were used for analyzing the antimicrobial susceptibility tests. The checkerboard technique was used for the in vitro assessment of fortimicin antibiotic combinations against 51 MDR P. aeruginosa and whole genome sequencing was used to determine the resistome of PDR isolate.ResultsOut of 51 MDR P. aeruginosa, the highest synergistic effect was recorded for a combination of fortimicin with β-lactam group as meropenem, ceftazidime, and aztreonam at 71%, 59% and 43%, respectively. Of note, 56.8%, 39.2%, and 37.2% of the tested MDR isolates that had synergistic effects were also resistant to meropenem, ceftazidime, and aztreonam, respectively. The highest additive effects were recorded for combining fortimicin with amikacin (69%) and cefepime (44%) against MDR P. aeruginosa. Resistome analysis of the PDR isolate reflected its association with the antibiotic resistance phenotype. It ensured the presence of a wide variety of antibiotic-resistant genes (β-lactamases, aminoglycosides modifying enzymes, and efflux pump), rendering the isolate resistant to all clinically relevant anti-pseudomonal agents.ConclusionFortimicin in combination with classical anti-pseudomonal agents had shown promising synergistic activity against MDR P. aeruginosa. Resistome profiling of PDR P. aeruginosa enhanced the rapid identification of antibiotic resistance genes that are likely linked to the appearance of this resistant phenotype and may pave the way to tackle antimicrobial resistance issues shortly.

In vitro development of resistance against antipseudomonal agents: comparison of novel β-lactam/β-lactamase inhibitor combinations and other β-lactam agents.

We subjected seven P. aeruginosa isolates to a 10-day serial passaging against five antipseudomonal agents to evaluate resistance levels post-exposure and putative resistance mechanisms in terminal mutants were analyzed by whole-genome sequencing analysis. Meropenem (mean, 38-fold increase), cefepime (14.4-fold), and piperacillin-tazobactam (52.9-fold) terminal mutants displayed high minimum inhibitory concentration (MIC) values compared to those obtained after exposure to ceftolozane-tazobactam (11.4-fold) and ceftazidime-avibactam (5.7-fold). Fewer isolates developed elevated MIC values for other β-lactams and agents belonging to other classes when exposed to meropenem in comparison to other agents. Alterations in nalC and nalD, involved in the upregulation of the efflux pump system MexAB-OprM, were common and observed more frequently in isolates exposed to ceftazidime-avibactam and meropenem. These alterations, along with ones in mexR and amrR, provided resistance to most β-lactams and levofloxacin but not imipenem. The second most common gene altered was mpl, which is involved in the recycling of the cell wall peptidoglycan. These alterations were mainly noted in isolates exposed to ceftolozane-tazobactam and piperacillin-tazobactam but also in one cefepime-exposed isolate. Alterations in other genes known to be involved in β-lactam resistance (ftsI, oprD, phoP, pepA, and cplA) and multiple genes involved in lipopolysaccharide biosynthesis were also present. The data generated here suggest that there is a difference in the mechanisms selected for high-level resistance between newer β-lactam/β-lactamase inhibitor combinations and older agents. Nevertheless, the isolates exposed to all agents displayed elevated MIC values for other β-lactams (except imipenem) and quinolones tested mainly due to alterations in the MexAB-OprM regulators that extrude these agents.

Uncovering the potentiality of quinazoline derivatives against Pseudomonas aeruginosa with antimicrobial synergy and SAR analysis.

Antimicrobial resistance has emerged as a covert global health crisis, posing a significant threat to humanity. If left unaddressed, it is poised to become the foremost cause of mortality worldwide. Among the multitude of resistant bacterial pathogens, Pseudomonas aeruginosa, a Gram-negative, facultative bacterium, has been responsible for mild to deadly infections. It is now enlisted as a global critical priority pathogen by WHO. Urgent measures are required to combat this formidable pathogen, necessitating the development of novel anti-pseudomonal drugs. To confront this pressing issue, we conducted an extensive screening of 3561 compounds from the ChemDiv library, resulting in the discovery of potent anti-pseudomonal quinazoline derivatives. Among the identified compounds, IDD-8E has emerged as a lead molecule, exhibiting exceptional efficacy against P. aeruginosa while displaying no cytotoxicity. Moreover, IDD-8E demonstrated significant pseudomonal killing, disruption of pseudomonal biofilm and other anti-bacterial properties comparable to a well-known antibiotic rifampicin. Additionally, IDD-8E's synergy with different antibiotics further strengthens its potential as a powerful anti-pseudomonal agent. IDD-8E also exhibited significant antimicrobial efficacy against other ESKAPE pathogens. Moreover, we elucidated the Structure-Activity-Relationship(SAR) of IDD-8E targeting the essential WaaP protein in P. aeruginosa. Altogether, our findings emphasize the promise of IDD-8E as a clinical candidate for novel anti-pseudomonal drugs, offering hope in the battle against antibiotic resistance and its devastating impact on global health.

Outcomes After Pseudomonas Prosthetic Joint Infections.

Pseudomonas species are a less common but devastating pathogen family in prosthetic joint infections (PJIs). Despite advancements in management, Pseudomonas PJIs remain particularly difficult to treat because of limited antibiotic options and robust biofilm formation. This study aimed to evaluate Pseudomonas PJI outcomes at a single institution and review outcomes reported in the current literature. All hip or knee PJIs at a single institution with positive Pseudomonas culture were evaluated. Forty-two patients (24 hips, 18 knees) meeting inclusion criteria were identified. The primary outcome of interest was infection clearance at 1 year after surgical treatment, defined as reassuring aspirate without ongoing antibiotic treatment. Monomicrobial and polymicrobial infections were analyzed separately. A focused literature review of infection clearance after Pseudomonas PJIs was performed. One-year infection clearance was 58% (n = 11/19) for monomicrobial PJIs and 35% (n = 8/23) for polymicrobial PJIs. Among monomicrobial infections, the treatment success was 63% for patients treated with DAIR and 55% for patients treated with two-stage exchange. Monotherapy with an oral or intravenous antipseudomonal agent (minimum 6 weeks) displayed the lowest 1-year clearance of 50% (n = 6/12). Resistance to antipseudomonal agents was present in 16% (n = 3/19), and two of eight patients with monomicrobial and polymicrobial PJIs developed resistance to antipseudomonal therapy in a subsequent Pseudomonas PJI. Polymicrobial infections (55%) were more common with a mortality rate of 44% (n = 10/23) at a median follow-up of 3.6 years. Pseudomonas infections often present as polymicrobial PJIs but are difficult to eradicate in either polymicrobial or monomicrobial setting. A review of the current literature on Pseudomonas PJI reveals favorable infection clearance rates (63 to 80%) after DAIR while infection clearance rates (33 to 83%) vary widely after two-stage revision.

Co-Occurrence of Gram-Negative Rods in Patients with Hematologic Malignancy and Sinopulmonary Mucormycosis.

Both Mucorales and Gram-negative rods (GNRs) commonly infect patients with hematological malignancies (HM); however, their co-occurrence is understudied. Therefore, we retrospectively reviewed the records of 63 patients with HM and proven or probable sinopulmonary mucormycosis at MD Anderson Cancer Center (Houston, Texas) from 2000-2020. Seventeen out of sixty-three reviewed patients (27.0%) had sinopulmonary co-occurrence of GNRs (most commonly Pseudomonas aeruginosa and Stenotrophomonas maltophilia) within 30 days of a positive Mucorales culture or histology demonstrating Mucorales species. Eight of seventeen co-isolations of Mucorales and GNRs were found in same-day samples. All 15 patients with GNR co-occurrence and reported antimicrobial data had received anti-Pseudomonal agents within 14 days prior to diagnosis of mucormycosis and 5/15 (33.3%) had received anti-Stenotrophomonal agents. Demographic and clinical characteristics of patients with and without GNR co-occurrence were comparable. Forty-two-day all-cause mortality was high (34.9%) and comparable in patients with (41.2%) and without (32.6%) GNR detection (p = 0.53). In summary, over a quarter of heavily immunosuppressed patients with sinopulmonary mucormycosis harbored GNRs in their respiratory tract. Although no impact on survival outcomes was seen in a background of high mortality in our relatively underpowered study, pathogenesis studies are needed to understand the mutualistic interplay of GNR and Mucorales and their influence on host responses.

Epidemiology and patterns of empiric antimicrobial therapy practice in patients with community-onset sepsis using data from a Japanese nationwide medical claims database—the Japan Sepsis Alliance (JaSA) study group

ObjectivesWe aimed to describe empiric antimicrobial options for patients with community-onset sepsis using nationwide real-world data from Japan. MethodsThis retrospective cohort study used nationwide Japanese data from a medical reimbursement system database. Patients aged ≥20 years with both presumed infections and acute organ dysfunction who were admitted to hospitals from the outpatient department or emergency department between 2010 and 2017 were enrolled. We described the initial choices of antimicrobials for patients with sepsis stratified by intensive care unit (ICU) or ward. ResultsThere were 1,195,741 patients with community-onset sepsis; of these, 1,068,719 and 127,022 patients were admitted to the wards and ICU, respectively. Third-generation cephalosporins and carbapenem were most commonly used for patients with community-onset sepsis. We found that 1.7% and 6.0% of patients initially used antimicrobials for methicillin-resistant Staphylococcus aureus coverage in the wards and ICU, respectively. Although half of the patients initially used antipseudomonal agents, only a few patients used a combination of antipseudomonal agents. Moreover, few patients initially used a combination of antimicrobials to treat methicillin-resistant Staphylococcus aureus and Pseudomonas sp. ConclusionThird-generation cephalosporins and carbapenem were most frequently used for patients with sepsis. A combination therapy of antimicrobials for drug-resistant bacteria coverage was rarely provided to these patients.

Comparative antibiogram of annual antimicrobial susceptibility trend in a tertiary care institution in Telangana with ICMR annual AMR report for the year 2021

Introduction: Antibiogram data can improve hospital antibiotic formulary decisions and local protocols such as surgical prophylaxis or empirical treatment guidelines. This study aims to compare the antimicrobial resistance (AMR) trends observed in our institution with the national data published by the Indian Council of Medical Research (ICMR). Methods: The annual antibiogram of all common clinical isolates received in the hospital in 2021 was constructed as per the consensus guidelines developed by the Clinical and Laboratory Standards Institute, and the antimicrobial susceptibility trends were compared with the Indian Council of Medical Research annual Antimicrobial Resistance Report for 2021. Results: A total of 719 first isolates (excluding duplicate isolates) of common organisms viz., Escherichia coli (n = 198), Klebsiella pneumoniae (n = 164), Pseudomonas aeruginosa (n = 70), methicillin-sensitive Staphylococcus aureus (MSSA) (n = 174), methicillin-resistant Staphylococcus aureus (MRSA) (n = 39), Enterococcus species (n = 74) were analyzed and described as in charts. Discussion: The percentage susceptibility of gram-positive isolates to vancomycin, linezolid, tetracycline, nitrofurantoin, and fosfomycin was comparable to the national ICMR AMR report, whereas there were differences in the susceptibility rates to other antimicrobial agents such as penicillin, ampicillin, erythromycin, clindamycin, and co-trimoxazole. The percentage susceptibility of P. aeruginosa isolates was comparable to the national ICMR AMR report for all anti-pseudomonal agents tested and analyzed. The gram-negative isolates showed better susceptibility rates to the beta-lactam antibiotics, fluoroquinolones, and carbapenems in comparison to the national ICMR AMR report. Conclusion: Analysis of antibiograms from different regions of our country would show us the trends and patterns of antimicrobial resistance.

The impact of implementation of rapid blood culture identification panels on antimicrobial optimization: a retrospective cohort study.

Determine the impact of limited implementation of a rapid blood culture identification (BCID) panel. Retrospective cohort study. From February to April 2022, positive blood cultures identified via e-Plex BCID (Roche, Carlsbad, CA) were compared to those identified using standard microbial identification techniques. The primary outcomes assessed were time to optimal therapy, time to de-escalation of anti-MRSA (methicillin-resistant Staphylococcus aureus) agents, and time to de-escalation of anti-pseudomonal agents. Additional analysis investigated the impact of the availability of antimicrobial stewardship program support. This study was conducted at Grady Health System, a large metropolitan safety-net hospital in the southeastern United States. A total of 253 blood cultures were included in this study (153 BCID and 100 standard). Blood culture identification use was associated with a reduction in median time to optimal antimicrobial therapy (43.4 vs 72.1 h, P < .001) and median time to de-escalation of anti-MRSA agents (27.7 vs 46.7 h, P = .006), and a trend towards reduction of median time to de-escalation of anti-pseudomonal agents (38.8 vs 54.8 h, P = .07). These reductions persisted when controlling for patient age, sex, intensive care unit status, Charlson Comorbidity Index, and antimicrobial stewardship program availability. Despite restricted use and lack of 24/7 antimicrobial stewardship program availability, BCID panel utilization was associated with earlier initiation of optimal therapy and pathogen identification with subsequent de-escalation of broad-spectrum antimicrobials, as compared to standard antimicrobial techniques. This suggests the potential for benefit from adopting novel diagnostic technologies outside of idealized fully-resourced settings.

“Microanalysis oriented bactericidal effect of the Suvarna Bhasma containing incinerated gold nanoparticles against the Pseudomonas Aeruginosa”

The antibacterial activity of synthetically prepared gold nanoparticles is well-known. In this unique study, the Suvarna bhasma containing the incinerated gold particles was tested for its bactericidal activity against Pseudomonas aeruginosa. The microanalysis of Suvarna bhasma was done through scanning electron microscopy, which revealed that, the gold particles' size ranged from 28 nm to 8.1 µm, forming particle agglomerates of a spherical shape with rough surfaces and heterogeneous distribution. The transition electron microscopy revealed that the particle size ranged between 2.2 to 18.96nm after the sonication of Suvarna bhasma. The energy dispersed X-ray analysis of the Suvarna bhasma sample revealed that it contained 86.3% gold, 3.1% oxygen, and 10.5% carbon. The X-ray diffraction findings of Suvarna bhasma showed four intense peaks of pure gold nanoparticles at (1 1 1), (2 0 0), (2 2 0), and (3 1 1) depicting that gold existed in a face-centered cubic crystalline lattice phase with an average particle size of 27.58 nm. The Minimum Inhibitory Concentration of Suvarna bhasma, through the broth microdilution method, was seen to be 312µg / mL against Pseudomonas aeruginosa ATCC 27853 grown in brain-heart infusion. In contrast, the Minimum Bactericidal Concentration was 1250 µg / mL. This result was substantiated by scanning electron microscopy analysis of the P. aeruginosa (10 x 6 colony forming units) treated with 1000 µg/mL of Suvarna bhasma, showing cellular structural damage as membrane rupture, cell shrinking and death. Hence, Suvarna bhasma may be one of the futuristic antipseudomonal agents.

Pseudomonasaeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group

ScopePseudomonas aeruginosa, a ubiquitous opportunistic pathogen considered one of the paradigms of antimicrobial resistance, is among the main causes of hospital-acquired and chronic infections associated with significant morbidity and mortality. This growing threat results from the extraordinary capacity of P. aeruginosa to develop antimicrobial resistance through chromosomal mutations, the increasing prevalence of transferable resistance determinants (such as the carbapenemases and the extended-spectrum β-lactamases), and the global expansion of epidemic lineages. The general objective of this initiative is to provide a comprehensive update of P. aeruginosa resistance mechanisms, especially for the extensively drug-resistant (XDR)/difficult-to-treat resistance (DTR) international high-risk epidemic lineages, and how the recently approved β-lactams and β-lactam/β-lactamase inhibitor combinations may affect resistance mechanisms and the definition of susceptibility profiles. MethodsTo address this challenge, the European Study Group for Antimicrobial Resistance Surveillance (ESGARS) from the European Society of Clinical Microbiology and Infectious Diseases launched the ‘Improving Surveillance of Antibiotic-Resistant Pseudomonas aeruginosa in Europe (ISARPAE)’ initiative in 2022, supported by the Joint programming initiative on antimicrobial resistance network call and included a panel of over 40 researchers from 18 European Countries. Thus, a ESGARS-ISARPAE position paper was designed and the final version agreed after four rounds of revision and discussion by all panel members. Questions addressed in the position paperTo provide an update on (a) the emerging resistance mechanisms to classical and novel anti-pseudomonal agents, with a particular focus on β-lactams, (b) the susceptibility profiles associated with the most relevant β-lactam resistance mechanisms, (c) the impact of the novel agents and resistance mechanisms on the definitions of resistance profiles, and (d) the globally expanding XDR/DTR high-risk lineages and their association with transferable resistance mechanisms. ImplicationThe evidence presented herein can be used for coordinated epidemiological surveillance and decision making at the European and global level.

A score to predict Pseudomonas aeruginosa infection in older patients with community-acquired pneumonia

BackgroundIn Thailand, the incidence of community-acquired pseudomonal pneumonia among 60- to 65-year-olds ranges from 10.90% to 15.51%, with a mortality rate of up to 19.00%. Antipseudomonal agents should be selected as an empirical treatment for elderly patients at high risk for developing this infection. The purpose of this study was to identify risk factors and develop a risk predictor for Pseudomonas aeruginosa infection in older adults with community-acquired pneumonia (CAP).MethodsA retrospective data collection from an electronic database involved the elderly hospitalized patients with P. aeruginosa- and non-P. aeruginosa-causing CAP, admitted between January 1, 2016, and June 30, 2021. Risk factors for P. aeruginosa infection were analysed using logistic regression, and the instrument was developed by scoring each risk factor based on the beta coefficient and evaluating discrimination and calibration using the area under the receiver operating characteristic curve (AuROC) and observed versus predicted probability (E/O) ratio.ResultsThe inclusion criteria were met by 81 and 104 elderly patients diagnosed with CAP caused by P. aeruginosa and non-P. aeruginosa, respectively. Nasogastric (NG) tube feeding (odd ratios; OR = 40.68), bronchiectasis (B) (OR = 4.13), immunocompromised condition (I) (OR = 3.76), and other chronic respiratory illnesses (r) such as atelectasis, pulmonary fibrosis, and lung bleb (OR = 2.61) were the specific risk factors for infection with P. aeruginosa. The “60-B-r-I-NG” risk score was named after the 4 abbreviated risk variables and found to have good predicative capability (AuROC = 0.77) and accuracy comparable to or near true P. aeruginosa infection (E/O = 1). People who scored at least two should receive empirically antipseudomonal medication.ConclusionsNG tube feeding before admission, bronchiectasis, immunocompromisation, atelectasis, pulmonary fibrosis and lung bleb were risk factors for pseudomonal CAP in the elderly. The 60-B-r-I-NG was developed for predicting P. aeruginosa infection with a high degree of accuracy, equal to or comparable to the existing P. aeruginosa infection. Antipseudomonal agents may be started in patients who are at least 60 years old and have a score of at least 2 in order to lower mortality and promote the appropriate use of these medications.

Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives.

Serious infections caused by nonfermenting Gram-negative bacteria (NF-GNB) pose a significant challenge for clinicians due to the limited treatment options available, which are frequently associated with issues of toxicity and unfavourable pharmacokinetic profiles. The aim of this review is to provide a brief overview of the existing data concerning the ongoing development of antiinfective agents targeting NF-GNB. Several agents exhibiting efficacy against NF-GNB are under clinical investigation. Durlobactam-sulbactam and cefepime-taniborbactam emerge as promising therapeutic avenues against carbapenem-resistant Acinetobacter baumanii. Cefepime-zidebactam may serve as a suitable treatment option for urinary tract infections caused by a wide range of NF-GNB. Cefepime-enmetazobactam demonstrates potent in vitro activity against various NF-GNB strains; however, its role as an anti-Pseudomonal agent is inadequately substantiated by available data. Xeruborbactam is a wide β-lactamase inhibitor that can be associated with a range of agents, enhancing in-vitro activity of these against many NF-GNB, including those resistant to newer, broader spectrum options. Lastly, murepavadin appears to be a potential pathogen-specific solution for severe Pseudomonas infections; however, additional investigation is necessary to establish the safety profile of this compound. Each of the novel molecules reviewed possesses an interesting range of in-vitro activity against NF-GNB. In addition, some of them have already been proved effective in vivo, underscoring their potential as future treatment options.