Multidrug-resistant Pseudomonas Research Articles

A Rapid Point-of-care Fluorescence Imaging Device Helps Prevent Graft Rejection Post Modified Radical Mastectomy

Abstract Pathogenic bacteria in wounds impede successful skin grafting. However, their detection relies on culture methods, which delay confirmation by several days. Real-time fluorescence imaging detects bacteria, allowing for rapid assessment and documentation. We herein report a post modified radical mastectomy, surgical site infection with multidrug-resistant Pseudomonas spp. that underwent repeated antibiotic therapy and debridement and eventually grafting. In this case, a real-time fluorescence imaging device helped prevent graft rejection.

Detection of Pyocin S and the Effects of Lactobacillus Acidophilus Cell-Free Supernatants on Multi-Drug Resistant Pseudomonas AeruginosaIsolated from Patients of Baghdad Hospitals

Detection of Pyocin S and the Effects of Lactobacillus Acidophilus Cell-Free Supernatants on Multi-Drug Resistant Pseudomonas AeruginosaIsolated from Patients of Baghdad Hospitals

Prevalence of multidrug-resistant bacterial infections in diabetic foot ulcers: A meta-analysis.

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.

Safety and efficacy of McCarey-Kaufman medium supplemented with colistin (polymyxin E) and amphotericin B in inhibiting the multidrug-resistant Pseudomonas aeruginosa using an ex vivo donor corneal infection model.

This study aimed to evaluate the efficacy and safety of McCarey-Kaufman (MK) medium supplemented with colistin and amphotericin B in inhibiting the growth of multidrug-resistant Pseudomonas (P.) aeruginosa , using an ex vivo experimental model with human donor corneas. Cadaveric human corneas deemed unsuitable for corneal transplantation were obtained, and MK media were supplemented with colistin and amphotericin B. Multidrug-resistant P. aeruginosa was cultured and used to infect the human donor corneas ex vivo . Infected corneas were placed in the MK media with additional antibiotics (colistin and amphotericin B) and the standard MK media, which served as the control arm for comparison. Corneal opacity due to infiltration and quantitative analysis of colony-forming units (CFUs) were assessed. The viability of the corneal endothelium was assessed using trypan blue staining. Corneas incubated in MK media supplemented with additional antibiotics showed less corneal opacification compared with those in standard MK media at both 48- and 96-hour (hr) time points. Quantitative analysis revealed a lower bacterial load and a significant reduction in CFU in the corneas incubated in MK media with additional antibiotics compared with the control group. At 48 hrs, there was 84% ( P value = 0.024) reduction in bacterial load, and at 96 hr, a 53% ( P value = 0.016) reduction was observed in comparison with those placed in standard MK media. The trypan blue staining tests revealed that the extent of endothelial cell loss in corneas incubated in supplemented MK media was comparable to the ones in standard MK media. The addition of colistin and amphotericin B to MK media demonstrated efficacy in inhibiting the growth of multidrug-resistant P. aeruginosa in an ex vivo cornea infection model. The supplemented media had no detrimental effect on the corneal endothelium. The findings suggest that supplementing the MK media with these broad-spectrum antimicrobial agents may help mitigate the risk of postoperative donor-related infection in the recipients by reducing and containing the load of microbial contamination in donor corneas.

Comparing antipseudomonal effects of honey samples with different geographical and botanical origin

Pseudomonas aeruginosa, resistant to all broad-spectrum antibiotics, is on the World Health Organization's list of first-priority critical pathogens. Using reserve antibiotics, such as colistin, highlights the imperative for safer, more effective alternatives to combat these superbugs.Medical-grade honey, known for its antibacterial properties and efficacy in wound healing, emerges as a promising candidate.This study analyzed eleven honey samples, diverse in geographical, botanical, and entomological origins, for their antipseudomonal activity using the agar well-diffusion method. Zones of inhibition growth were measured in mm. The function switch was used to approximate the zones of inhibition values for antibacterial activity expressed as minimal inhibitory concentrations MIC99, MIC90, and MIC80, the lowest concentration, killing 99 %, 90 %, and 80 % of organisms, respectively. The authenticity and quality of honey samples complied with the European Commission, Codex Alimentarius, and Serbia Rulebook standards for honey. Melissopalynological analysis ensured the botanical authenticity of tested honey samples. A unique aspect of this research is that it included a honey sample from Serbia's Zlatar mountain region, harvested from Apis mellifera carnica bee colonies. The study's findings reveal that wild-type and multidrug-resistant Pseudomonas clinical isolates were susceptible to the tested honey samples. Honeydew honey from Zlatar showed the highest antibacterial activity on both tested bacteria. Honeydew and buckwheat honey from Zlatar yielded larger inhibition zones than manuka honey. Artificial honey showed no antibacterial effect.In conclusion, this research suggests the potential of honey, particularly from Zlatar, as an alternative therapy for treating infected wounds, warranting further investigation into its antimicrobial efficacy.

The impact of COVID-19 on microbiological profile and antibiotic consumption in ICU: a retrospective study in an infectious disease hospital in Brazil

BackgroundThe COVID-19 pandemic has triggered crises in the public health sector that have complex and multifaceted interrelationships with antimicrobial resistance. It is important to evaluate the impact of COVID-19 on microbiological profile, antibiotic and alcohol gel consumption in Intensive Care Units (ICU). MethodsThis is a retrospective study undertaken in an infectious disease hospital located in Bahia/Brazil during three periods: from March 2019 to February 2020; from March 2020 to February 2021; and from March 2021 to February 2022. It was evaluated the incidence density of Candida spp and of multidrug-resistant Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE group) in blood, urine and tracheal secretion isolated 48 h after the patient's admission to the ICU, as well as the use of alcohol gel (in milliliters) and consumption of antibiotics in Defined Daily Dose (DDD) per 1,000 ICU patient-days in the previous year and in the first two years of COVID-19 pandemic. ResultsThere was an increase in Candida spp. (5.81, p < 0.001, IRR = 10.47, 95 % CI 2.57‒42.62) and in carbapenem-resistant A. baumannii in clinical cultures (4.71, p < 0.001, IRR = 8.46, 95 % CI 2.07‒34.60), the latter mainly in tracheal secretions (3.18, p= 0.02, IRR = 11.47, 95 % CI 1.58‒83.39). A rise in the consumption of ceftriaxone and piperacillin-tazobactam, along with an increase in the utilization of alcohol gel were observed. ConclusionThe shifting microbiological profile can be attributed to both the unique characteristics of patients with COVID-19 and the adjustments made to healthcare facilities' structural and work routines. Understanding these changes is essential in addressing the accelerated impact of antimicrobial resistance during the pandemic. Therefore, conducting thorough reviews of institutional practices and routines becomes critical in mitigating the consequences of antimicrobial resistance and its implications for patient care.

2814. The Impact of Novel Antibiotics on Curbing Antimicrobial Resistance and Infection Spread a Dynamic Modeling Study

Abstract Background Antimicrobial resistance (AMR) is a growing global concern. Novel antibiotics (ABXs) target resistant pathogens causing gram-negative (GN) bacterial infections. This study assesses the broader impact of novel ABX use on the US healthcare system, including preventing the onward spread of infections and reducing the level of high-threat AMR. Methods A stochastic dynamic transmission model was developed to simulate the interaction between infection transmissibility, bacterial resistance development, and multiple lines of ABX. Included infection types were intra-abdominal infections, urinary tract infections and hospital-acquired /ventilator-associated pneumonia. Included AMR types were carbapenem-resistant and ESBL-producing enterobacterales (CRE and ESBLE), and multi-drug resistant pseudomonas aeruginosa (MDRP). The model has compartments for non-infected, colonized, or infected patients, with a sensitive or resistant strain in a US hospital. Infected patients receive antibiotics resulting in infection clearance or use of an alternate ABX class. Sensitive pathogens gain resistance due to drug pressure or conversely could lose resistance. Ordinary differential equations were used to estimate compartment membership. The primary data source was the Premier healthcare database (172 hospitals, 2016-2020). The model examined the potential reduction in AMR levels and avoided hospital infections, by comparing two scenarios: targeted use of novel ABX for specific AMR types and the status quo with limited novel ABX use. Results When even novel ABXs are reserved as the 2nd or 3rd line of treatment, compared to the status quo, it could result in a ∼1.5% reduction in hospital infections and a change in CRE, ESBLE, and MDRP by −2.5%, −3.6%, and −2.1%, respectively, on an annual basis. The cumulative impact of novel ABXs over 5-10 years was much larger but subject to higher prediction uncertainty. The primary driver of results are infection clearance rates, risk of resistance gain on various ABX, and uptake of novel ABX. Conclusion Targeted use of novel ABXs for resistant pathogens could lead to improved, earlier infection clearance with most types of infections and pathogens, thereby reducing infection transmission and rise of high-threat AMR in the long-term. Disclosures Apoorva Ambavane, PhD, Merck &amp; Co., Inc: Grant/Research Support Michal Litkiewicz, MSc, Merck &amp; Co., Inc: Grant/Research Support Aditya Sardesai, MSc, CSL Seqirus: Advisor/Consultant|Merck &amp; Co. Inc: Grant/Research Support|Merck &amp; Co. Inc: Grant/Research Support Diana Teloian, MA, Merck &amp; Co., Inc: Grant/Research Support Engels N. Obi, PhD, Merck &amp; Co Inc: Employee Joe Yang, PhD, Merck &amp; Co., Inc: Employee|Merck &amp; Co., Inc: Stocks/Bonds

Comparative Study on the Antimicrobial Activities and Metabolic Profiles of Five Usnea Species from the Philippines.

The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics. Hence, there is a need to search for new sources of antibiotics that either exhibit novel structures or express a new mechanism of action. The lichen Usnea, with its wide range of unique, biologically potent secondary metabolites, may solve this problem. In this study, Usnea species were collected in the Northern Philippines, identified through combined morphological and biochemical characterization, and tested for antimicrobial activities against the multidrug-resistant ESKAPE pathogens, i.e., Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae, two standard antibiotic-sensitive test bacteria, and a yeast. A total of 46 lichen specimens were collected and later identified as Usnea baileyi (10), U. diffracta (10), U. glabrata (12), U. longissima (4), and U. rubicunda (10). The results show that the crude extracts of the Usnea species exhibited promising in vitro inhibitory activities against standard antibiotic-sensitive (E. faecalis ATCC 29212) and multidrug-resistant (methicillin-resistant S. aureus and E. faecalis) Gram-positive bacteria. Additionally, lichen compounds of representative specimens per species were identified and profiled using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). The detection of lichen acids (LA) via HPLC showed the presence of 24 peaks of lichen acids. TLC-bioautography identified the bioactive lichen acids as alectronic acid, connorstictic acid, consalazinic acid, diffractaic acid, echinocarpic acid, erythrin acid, galbinic acid, hypoconstictic acid, hyposalazinic acid, hypostictic acid, lobaric acid, menegazzaic acid, micareic acid, pannarin, salazinic acid, stictic acid, and usnic acid. Our study highlighted the wide spectrum of opportunities for using lichens for the discovery of potential antimicrobial agents.

Crossroads of Antimicrobial and Diagnostic Stewardship: Assessing Risks to Develop Clinical Decision Support to Combat Multidrug-Resistant Pseudomonas.

Early detection of multidrug-resistant Pseudomonas aeruginosa (MDRP) remains challenging. Existing risk prediction tools are difficult to translate to bedside application. The goal of this study was to develop a simple electronic medical record (EMR)-integrated tool for prediction of MDRP infection. This was a mixed-methods study. We conducted a split-sample cohort study of adult critical care patients with P aeruginosa infections. Two previously published tools were validated using c-statistic. A subset of variables based on strength of association and ease of EMR extraction was selected for further evaluation. A simplified tool was developed using multivariable logistic regression. Both c-statistic and theoretical trade-off of over- versus underprescribing of broad-spectrum MDRP therapy were assessed in the validation cohort. A qualitative survey of frontline clinicians assessed understanding of risks for MDRP and potential usability of an EMR-integrated tool to predict MDRP. The 2 previous risk prediction tools demonstrated similar accuracy in the derivation cohort (c-statistic of 0.76 [95% confidence interval {CI}, .69-.83] and 0.73 [95% CI, .66-.8]). A simplified tool based on 4 variables demonstrated reasonable accuracy (c-statistic of 0.71 [95% CI, .57-.85]) without significant overprescribing in the validation cohort. The risk factors were prior MDRP infection, ≥4 antibiotics prior to culture, infection >3 days after admission, and dialysis. Fourteen clinicians completed the survey. An alert providing context regarding individual patient risk factors for MDRP was preferred. These results can be used to develop a local EMR-integrated tool to improve timeliness of effective therapy in those at risk of MDRP infections.

Clinical outcomes of ceftolozane-tazobactam dosing in patients with sepsis undergoing renal replacement therapies.

A retrospective descriptive study conducted at our institution between May 1, 2017, and March 15, 2022. The primary endpoint was to determine the clinical cure for patients who received C/T for documented infection while on RRT. The secondary endpoints were the microbiologic cure, 30-day infection recurrence, and 30-day crude mortality. Of the 27 patients who met the inclusion criteria, 17 (63%) were males, median age was 69 (62 - 82) years, and weight 67 (57 - 79) kg. The majority of patients had pneumonia 19 (70.4%) followed by bacteremia 5 (18.5%). Multidrug resistant Pseudomonas spp. was the causative organism of infection in 22 subjects (81.5%). Clinical cure was achieved in 17 subjects (63%). Of the 14 subjects who had their culture repeated, 10 (71.4%) patients had microbiologic cure vs. 4 (28.5%) patients who had a microbiologic failure (p = 0.327). 30-day infection recurrence occurred in 6 (35.3%) patients of the clinical cure group and 2 (20%) patients in the clinical failure group (p = 0.362), while mortality occurred in 5 (29.4%) subjects vs. 7 (70%) in both groups, respectively (p = 0.049). The most frequently used doses of C/T were 1.5 g IV q8h while undergoing continuous venovenous hemodiafiltration and 0.75 g IV q8h while undergoing hemodialysis (p = 0.209). The median duration of therapy was 9 (4.5 - 13) days in the clinically cured group vs. 5 (3.75 - 5.5) days in those who had clinical failure (p = 0.038). There was no adverse event reported using these doses during the study period. The used doses of C/T in this study were higher than those approved by the U.S. FDA, while clinical success is uncertain. Larger outcomes and pharmacokinetics studies are needed to establish effective dosing and therapy duration.

Presence of T3SS (exoS, exoT, exoU and exoY), susceptibility pattern and MIC of MDR-Pseudomonas aeruginosa from burn wounds.

The emergence of resistance is a major public health and clinical issue, particularly in pathogens causing nosocomial infections. Recently, there is the emergence of Pseudomonas aeruginosa resistance to different broad-spectrum antibiotics. The current study was designed to find out the prevalence of multi-drug resistant (MDR) P. aeruginosa in burn patients, the antibiotic susceptibility pattern of MDR Pseudomonas, and to determine the Minimum Inhibitory Concentration (MIC) of the effective antimicrobials. The assessment of virulence genes (exoT, exoS, exoY and exoU) was also achieved through PCR. In the current study wound swabs were collected from 160 burn patients from two burn units (MTI-Govt. Lady Reading Hospital and MTI-Khyber Teaching Hospital). Out of these 160 samples, 26 samples (16.25%) were positive for P. aeruginosa. Per patients, one isolate was included in the current study. Antibiotic susceptibility pattern showed all P. aeruginosa isolates were 100% resistant to amoxicillin-clavulanic acid, 84.62% resistance to Cefepime, and Ceftazidime, and 76.92% resistance to Amikacin, Aztreonam, and Ciprofloxacin. Whereas the lowest resistance was observed to Imipenem and Piperacillin-Tazobactam (53.85%), Colistin Sulfate (23.08%), and Polymyxin-B (15.38%). Regarding the prevalence of MDR, 22 (84.61%) isolates out of 26 were found to be MDR-P. aeruginosa. For MDR-P. aeruginosa, the MIC range was 1-2 µg/mL against Polymyxin-B, 2-8 µg/mL against Colistin sulfate, 16-1024 µg/mL against Imipenem and 128-1024 µg/mL against Piperacillin-Tazobactam. 100% of the isolates carried exoT, 88.46% carried exoY, and 57.69% and 38.46% carried exoU and exoS, respectively. These findings further emphasize the need for antibiotic discipline and to follow the recommended hospital antibiotic policy to prevent the proliferation of MDR strains of P. aeruginosa in the community.

CASE REPORT: Multidrug-resistant Pseudomonas keratitis and sequential endophthalmitis treated with chlorhexidine and piperacillin-tazobactam

Purpose To report the clinical course and treatment strategies employed in management of a case of multidrug-resistant Pseudomonas aeruginosa keratitis progressing to endophthalmitis. The drug-resistant strain was later traced to use of contaminated EzriCare Artificial Tears in a multi-state cluster outbreak. Observations A 57-year-old male patient with a history of Descemet stripping automated endothelial keratoplasty was referred for a culture-positive Pseudomonas corneal ulcer in the right eye that had been treated with several weeks of topical moxifloxacin, fortified vancomycin and tobramycin, and intravitreal injections for endophthalmitis. His cornea was cultured off of antibiotics and grew only rare Propionibacterium acnes. Topical antibiotics and steroids were reduced, but his condition rapidly deteriorated with leading to corneal melt, perforation, and endophthalmitis. Repeat corneal cultures and sensitivity analyses revealed growth of a strain of Pseudomonas aeruginosa that was resistant to fluoroquinolones, aminoglycosides, cephalosporins, monobactams, and carbapenems, and only intermediate susceptibility to piperacillin-tazobactam. The patient underwent a therapeutic penetrating keratoplasty and was subsequently initiated on an intensive regimen of topical chlorhexidine and polymyxin-B/trimethoprim. He also underwent a pars plana vitrectomy with anterior chamber washout, followed by serial injections of intravitreal piperacillin-tazobactam at a dose of 225 mg/0.1 mL. After 8 weeks of intensive treatment, there was gradual with healing of his ocular surface, regression of his hypopyon and posterior inflammation, and no signs of recurrent infection. A public health investigation ultimately revealed that his infection was one of several cases involved in a multistate cluster outbreak of extensively drug-resistant Pseudomonas ocular infections that were traced to the use of contaminated EzriCare Artificial Tears. Conclusions and Importance Multidrug-resistant keratitis and endophthalmitis caused by multidrug-resistant Pseudomonas keratitis requires consideration of nonconventional antimicrobial agents and experimental therapeutic alternatives. Topical chlorhexidine and intravitreal piperacillin-tazobactam are currently nonconventional therapies in the context of bacterial keratitis and endophthalmitis, but were safe and effective in the management of multidrug-resistant Pseudomonas aeruginosa ocular infection.

P25 Ceftazidime/avibactam and cefiderocol use in adults in a South London Trust

Abstract Background NHS England now subsidizes pharmaceutical firms to invest in new antibiotic development. Currently, this applies to cefiderocol and ceftazidime/avibactam for treatment of patients with severe bacterial infections non-responsive to other antibiotics. The aims are to reduce the risk of resistance and protect the longevity of antimicrobials by restricting use to certain patients with sepsis, hospital/ventilator-associated pneumonia and bloodstream infections. Acute hospital trusts bear most of the drug cost but receive a 19%–33% discount. Methods Pharmacy records for ceftazidime/avibactam or cefiderocol from July to December 2022 were accessed. Medical notes and laboratory systems were interrogated for clinical information as part of required Blueteq reporting. Results 15 prescriptions of cefiderocol and ceftazidime/avibactam were reviewed in 14 patients. The total number of days of therapy was 268 (112 + 156 for cefiderocol and ceftazidime/avibactam respectively). Median treatment duration was 11.5 (IQR 7–16.5) and 10 (IQR 5–22) days for cefiderocol and ceftazidime/avibactam, respectively. All infections were considered healthcare associated. Target organisms were Enterobacterales (39%), Pseudomonas spp. (28%), Acinetobacter spp. (11%) and Stenotrophomonas spp. (22%) (Figure 2). Twenty-one percent had polymicrobial infections and 50% of patients received adjunctive antibiotics (25% cefiderocol and 71% ceftazidime/avibactam). In-hospital mortality was 64%. All Enterobacterales, Acinetobacter and Pseudomonas isolates underwent phenotypic carbapenem susceptibility testing, and 100% of these were found to be resistant to at least one carbapenem. Where phenotypic carbapenem resistance was detected in Enterobacterales, reflex carbapenemase testing in accordance with laboratory protocol was performed for 71%, with a gene detected in 71% of these. For carbapenem-resistant Acinetobacter isolates, reflex ceftazidime/avibactam testing in accordance with laboratory protocol was performed in 100%. There is no local protocol in place for reflex cefiderocol/ceftazidime/avibactam susceptibility testing in multidrug-resistant Pseudomonas isolates. The median turnaround time from sample collection to result authorization was 2 (IQR 1.75–10) and 7 (IQR 2–9) days for cefiderocol and ceftazidime/avibactam, respectively. Use was empirical at the time of prescription in 40% of cases and appropriate (based on final AST results) in 80%. An infection specialist was involved in the initial prescription in all cases, and bedside review occurred in all cases. Conclusions Use of high-cost antimicrobials is currently led by infection specialists in our Trust, often empirical initially but usually appropriate based on final results. Practices around reflex expanded susceptibility of clinically significant MDR Gram negatives, and carbapenemase testing of Enterobacterales should be improved. Optimizing these processes should be prioritized as the infection sciences laboratory moves to a central hub.

Selective Photothermal Therapy Based on Lipopolysaccharide Aptamer Functionalized MoS2 Nanosheet‐Coated Gold Nanorods for Multidrug‐Resistant Pseudomonas aeruginosa Infection (Adv. Healthcare Mater. 15/2023)

Targeted Photothermal Therapy Combined with the outstanding photothermal conversion efficiency of gold nanorods (AuNRs), superior biocompatibility of molybdenum disulfide (MoS2) nanosheets, and strong specificity of lipopolysaccharides aptamer (LPS apt), composite nanorods (MoS2-AuNRs-apt) exhibit excellent therapeutic effects for multidrug-resistant pseudomonas aeruginosa and excess M1 macrophage in vitro, as well as infectious wounds in vivo. This work is found in article 2202794 by Yongyu Rui, Lei Zheng, and co-workers.

Neutropenic Sepsis and Challenges to Combat

Neutropenic sepsis (NS) is a common and predictable complication of bone marrow disorders and cytotoxic chemotherapy. After intensive chemotherapy, the incidence of NS is about 70–100% during the neutropenic phase. Patients with neutropenia are vulnerable to invasive infections, which can be rapidly overwhelming, causing septic shock and death. The epidemiology of sepsis in industrialized countries is mainly influenced by the age of the population and the increasing prevalence of comorbidities, such as chronic organ dysfunctions, non-cancer-related immunosuppressive diseases, or cancer itself. Patients with cancer are at more than 10 times higher risk for sepsis than the general population, with some variability according to the cancer types. There is frequent frustration among physicians caring for patients with neutropenic sepsis. Infections are a frequent complication in leukopenic patients, affecting an estimated 24% of patients after chemotherapy for hematologic diseases or solid organ tumors. Bloodstream infections (BSIs) are the most frequent infection in febrile neutropenic, onco-hematological patients, with incidence rates spanning from 10% to 38%. Septic shock is the most severe clinical presentation form of such infections. This is becoming a cause for growing concern due to several factors. Rates of Gram-negative bacilli (GNB) in oncohematological patients are progressively increasing. It is shown that ~50% of bacteremia in cancer patients was caused by GNB, among which almost 14% were MDR GNB. This could impact a greater percentage of patients presenting with septic shock. The widespread emergence and dissemination of multidrug-resistant Gram-negative bacilli, which are a common cause of infection and sepsis in patients with cancer, is of great concern. Several investigators have reported high rates of bacteremia due to extended-spectrum â-lactamase (ESBL)-producing Enterobacterales, MDR Pseudomonas aeruginosa (MDR-PA), and carbapenem-resistant Enterobacterales. Additionally, empirical antibiotic therapy is challenging in the era of emerging multidrug-resistant (MDR) GNB. Indeed, inappropriate empirical antibiotic therapy (IEAT) has been associated with increased mortality in patients with febrile neutropenia and BSI. Neutropenic sepsis is a medical emergency in which broad-spectrum antibiotics must be given without delay. Delaying treatment in neutropenic sepsis may increase the risk of death. â-Lactam/â-lactamase inhibitors (BL/ BLIs) and carbapenems are often considered for the treatment of sepsis when the main suspected pathogens are Gram-negative bacteria, because of their broad spectrum of coverage. Ceftazidime avibactam is a new molecule available against these bugs. It is a novel combination of ceftazidime (thirdgeneration cephalosporin) and avibactam (novel, nonâ- lactam â-lactamase inhibitor) which covers ESBL isolates like E Coli &amp; K. Pneumoniae, MDR Pseudomonas aeruginosa, and CRE. Ceftazidime and avibactam are now playing a crucial role in combating MDR gram-negative infections in sepsis patients. Many international guidelines recommend using early ceftazidime and avibactam in sepsis patients to achieve better outcomes and reduce volatility. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 197-198

Impact of a real-time diagnostic and antimicrobial stewardship workflow on time to appropriate therapy for infections caused by multidrug-resistant Gram-negative organisms

IntroductionMultidrug-resistant (MDR) Gram-negative organisms cause life-threatening infections, and the incidence is rising globally. Timely therapy for these infections has a direct impact on patient survival. This study aimed to determine the impact of a multidisciplinary diagnostic and antimicrobial stewardship (AMS) workflow on time to appropriate therapy (TAP) for these infections using novel beta-lactam/beta-lactamase inhibitors. MethodsThis was a retrospective quasi-experimental study of adult patients with carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas (MDR PsA) infections at a 1500 bed university hospital. Included patients who received ≥ 72 hours of ceftazidime-avibactam (CZA) or ceftolozane-tazobactam (C/T) from December 2017 to December 2019. During the pre-intervention period (December 2017 to December 2018), additional susceptibilities (including CZA and C/T) were performed only upon providers’ request. In 2019, reflex algorithms were implemented for faster identification and testing of all CRE/MDR PsA isolates. Results were communicated in real-time to the AMS team to tailor therapy. ResultsA total of 99 patients were included, with no between-group differences at baseline. The median age was 60 years and 56 (56.7%) were in intensive care at the time of culture collection. Identified organisms included 71 (71.7%) MDR PsA and 26 CRE, of which 18 were carbapenemase producers (Klebsiella-producing carbapenemase = 12, New Delhi metallo-β-lactamase = 4, Verona integron-encoded metallo-β-lactamase = 2). The most common infections were pneumonia (49.5%) and bacteraemia (30.3%). A decrease was found in median TAP (103 [IQR 76.0–156.0] vs. 75 [IQR 56–100] hours; P < 0.001). Median time from culture collection to final susceptibility results was shorter in the post-intervention group (123 vs. 93 hours; P < 0.001). ConclusionThis study identified improvement in TAP in MDR PsA and CRE infections with implementation of a reflex microbiology workflow and multidisciplinary antimicrobial stewardship initiatives.

EVALUATION OF POLYMYXCIN B IN COMBINATION WITH CIPROFLOXACIN ANTIBIOTICS AGAINST PSEUDOMONAS AEURUGINOSA

The fact that bacteria may resist various antimicrobials because they have various antimicrobial-associated genes makes them the primary cause of human infection.Therefore, this study aimed to determine the bacteria resistance to antibiotics.By using the disc diffusion method,antibiotics were tested for their susceptibility to microbes.Pseudomonas aeruginosa isolates are completely sensitive to Ciprofloxacin and Polymyxin B sulfate.This study investigated the in vitro activity of the combination of Ciprofloxacin with Polymyxin B sulphate (PMB) at different concentrations against multidrug-resistant (MDR) Pseudomonas aeruginosa.The combination effect of Ciprofloxacin and Polymyxin B sulphate antibiotics was evaluated by measuring the zone of inhibition using disc diffusion method. The minimum inhibitory concentration (MIC) of antibiotics was determined using broth microdilution.Our findings suggest that the combination of Ciprofloxacin and Polymyxin B sulphate has a synergistic effect on Pseudomonas aeruginosa. As a result, the synergistic combination reported in this study needs to be tested further in vivo before being used in clinical trials

Clinical settings, management and factors affecting outcomes in multi and extensively-drug resistant Pseudomonas endophthalmitis.

To report the clinical settings, management and factors affecting outcomes in multi-drug resistant (MDR) and extensively-drug resistant (XDR) Pseudomonas endophthalmitis. Retrospective, consecutive, non-comparative interventional case series. Cases of MDR and XDR Pseudomonas endophthalmitis from January 2012 to December 2020 treated at our tertiary eye care center were included. Data collected included clinical data, anatomic and functional outcome, isolated micro-organisms, and culture sensitivity. This study included 29 eyes of 29 patients with MDR/XDR Pseudomonas endophthalmitis. Mean age at presentation was 60.27 ± 14.9 years (median 63). Commonest clinical setting was acute post-operative endophthalmitis in 27 cases (93.1%). Concurrent corneal infiltrate was present in 11 eyes (37.9%). Initial intervention in 19 eyes (65.5%) was vitrectomy, 2 of which underwent endoscopic pars plana vitrectomy. Mean number of interventions was 3.34 ± 1.44 (median 4). Mean follow up was 3.25 ± 3.07 months (median 2). Sensitivity to ceftazidime was 48.28%. All isolates were sensitive to colistin. Mean visual acuity at last follow up in logMAR was 2.64 ± 1.48 (median 3.5). Seven eyes (24.13%) were NPL (nil perception of light) at the last follow up. Two eyes (6.9%) underwent evisceration. Nine eyes (31.03%) had a favourable anatomic and functional outcome. Eyes without a corneal infiltrate at presentation were found to have a favourable anatomic and favourable functional outcome (OR 11.91, P < 0.04, CI 1.08 to 130.93). Corneal involvement at presentation is associated with poorer outcomes in MDR and XDR Pseudomonas endophthalmitis. There is a potential role of higher newer antibiotics especially colistin in the management of these cases.

Pseudomonas Bacteremia in Children: Clinical and Microbiologic Features and Risk Factors of Mortality: A Retrospective Cohort Study.

Pseudomonas bacteremia is most commonly acquired in hospital. The aim of this study was to investigate the clinical features and antibiotic susceptibility, mortality rate and risk factors of mortality in children with Pseudomonas bacteremia. A retrospective cohort study that included children 18 years of age or younger admitted to a tertiary hospital with Pseudomonas bacteremia between 2005 and 2020. A total of 196 patients with Pseudomonas bacteremia were identified. The proportional rate of Pseudomonas bacteremia was 33.9/100,000 hospital days. Underlying disease was documented in 81.1% of patients, 61% had hemato-oncological disease. Pseudomonas bacteremia was healthcare related in 180 (91.8%) episodes. Multidrug-resistant (MDR) Pseudomonas accounted for 16 (8.2%) and difficult-to-treat organism to 3 (1.5%) of all isolates. Thirty-day mortality was reported in 27 (13.8%) patients, all had Pseudomonas aeruginosa . In multivariate regression analysis, the first model showed that younger age [ P = 0.038, odds ratio (OR) = 1.095, 95% confidence interval (CI): 1.005-1.192] and inappropriate empiric antibiotic treatment ( P = 0.004, OR = 3.584, 95% CI: 1.490-8.621) were significantly associated with higher mortality. The second model also showed higher morality in younger age ( P = 0.021, OR = 1.114, 95% CI: 1.016-1.221) and MDR isolates ( P = 0.001, OR = 9.725, 95% CI: 2.486-38.039). Significant morbidity and mortality due to Pseudomonas bacteremia, but relatively lower mortality than previously published. Although young age, MDR isolates and inappropriate antibiotic treatment have been associated with increased mortality, these factors, especially with low prevalence of MDR isolates, may reflect the baseline mortality rate in vulnerable hosts with continuous contact with healthcare facilities facing such severe infection, and more efforts should be made to emphasize infection control practices to prevent such severe infection.

Antimicrobial susceptibility study and molecular epidemiology of ceftazidime/avibactam against Pseudomonas aeruginosa collected from clinical patients in PR China (2004-2021).

Introduction. The increasing prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa worldwide is a significant global public health concern. Ceftazidime/avibactam (CZA) has been considered a novel promising β-lactam/β-lactamase inhibitor combination antibiotic against difficult-to-treat P. aeruginosa isolates. Big data studies on CZA susceptibility against P. aeruginosa have been limited.Gap statement. Production of metallo-β-lactamases was the most prevalent resistance mechanism for P. aeruginosa against CZA.Aim. To assess the in vitro activity of CZA against P. aeruginosa strains and the relevant resistance mechanisms.Methodology. One thousand three hundred and sixty-three P. aeruginosa isolates were collected from 2004 to 2021. Antimicrobial susceptibility testing was carried out for commonly used antipseudomonal drugs via the broth microdilution method. Polymerase chain reaction (PCR) or whole-genome sequencing were performed to analyse the most common carbapenemase genes. Molecular epidemiology was analysed by uploading the sequencing data to the Center for Genomic Epidemiology website.Results. Antimicrobial susceptibility testing showed that CZA and lipopeptides are the most active antibiotics against P. aeruginosa isolates. PCR and genome sequencing revealed that the most prevalent resistance mechanism for P. aeruginosa against CZA was the production of metallo-β-lactamases. None of the bla PDC mutations were found to be associated with avibactam resistance.Conclusion. Our findings revealed that CZA and lipopeptides are the most active antibiotics against P. aeruginosa isolates. The most prevalent resistance mechanism for P. aeruginosa against CZA was the production of metallo-β-lactamases, and none of the bla PDC mutations were found to be associated with avibactam resistance.