Broad-spectrum Antimicrobials Research Articles

Smartphone-based polydiacetylene colorimetric sensor for point-of-care diagnosis of bacterial infections

The rapid progress in point-of-care testing (POCT) has become a promising decentralized patient-centered approach for the control of infectious diseases, especially in resource-limited settings. POCT devices should be inexpensive, rapid, simple operation and preferably require no power supply. Here, we developed a simple bacterial sensing platform that can be operated by a smartphone for bacteria identification and antimicrobial susceptibility testing (AST) based on using a polydiacetylene (PDA) arrayed membrane chip. Each PDA array produced a unique color ‘fingerprint’ pattern for each bacteria based on different modes of action of toxins from bacteria on biomimetic lipid bilayers within PDA-lipid assemblies. We show that the PDA-based device can detect viable cells of bacteria as low as 104 ​CFU/mL within 1.5 ​h compared with several days of conventional bacterial identification, with the aid of a smartphone app. The device can also be used for an antimicrobial susceptibility test (AST) for at least two broad-spectrum antimicrobials within 4 ​h and provide identification of antimicrobial susceptibility and resistance, enabling the selection of appropriate therapies. This PDA-based sensing platform provides an alternative way for bacterial detection and could be used as a portable and inexpensive POCT device for the rapid detection of bacterial infection in limited-resource settings.

PACTA-Ped: Antimicrobial stewardship programme in a tertiary care hospital in Spain

IntroductionFighting against antimicrobial resistance is a current priority, and further efforts need to be made to improve antimicrobial prescribing and reduce the spread of infections in paediatric care settings. MethodsWe conducted a prospective longitudinal study on the use of antimicrobials from the time the antimicrobial stewardship programme (ASP) was introduced in January 2016 to December 2017 (period 2 [P2]) in our children’s hospital. We compared the obtained results on antimicrobial prescribing with retrospective data from the period preceding the introduction of the ASP (2014–2015, period 1 [P1]). The sample consisted of paediatric inpatients who received broad-spectrum antimicrobials, antifungals or intravenous antibiotherapy lasting more than 5 days. We compared the use of antimicrobials in P1 versus P2. ResultsA total of 160 patients were included during P2. The antibiotics for which a recommendation was made most frequently were meropenem (41.6%) and cefotaxime (23.4%). In 45% of care episodes, the consultant recommended “no change” to the prescribed antimicrobial. The final rate of acceptance of received recommendations by the prescribing physicians was 89%. We found average decreases of 27.8% in the days of treatment per 1000 inpatient days and 22.9% in the number of antimicrobial starts per 1000 admissions in P2. The use of carbapenems, cephalosporins and glycopeptides decreased in P2 compared to P1. The average annual cost of antimicrobial treatment decreased from є150 356/year during P1 to є98 478/year in P2. ConclusionOur ASP achieved a significant decrease in the use of broad-spectrum antibiotics and antifungals. The costs associated with antimicrobial prescribing decreased following the introduction of the ASP, which was a cost-effective action in this study period.

PACTA-Ped: programa de optimización de antimicrobianos en un hospital de tercer nivel en España

IntroductionFighting against antimicrobial resistance is a current priority, and further efforts need to be made to improve antimicrobial prescribing and reduce the spread of infections in paediatric care settings. MethodsWe conducted a prospective longitudinal study on the use of antimicrobials from the time the antimicrobial stewardship programme (ASP) was introduced in January 2016 to December 2017 (period 2 [P2]) in our children's hospital. We compared the obtained results on antimicrobial prescribing with retrospective data from the period preceding the introduction of the ASP (2014–2015, period 1 [P1]). The sample consisted of paediatric in patients who received broad-spectrum antimicrobials, antifungals or intravenous antibiotherapy lasting more than 5 days. We compared the use of antimicrobials in P1 versus P2. ResultsA total of 160 patients were included during P2. The antibiotics for which a recommendation was made most frequently were meropenem (41.6%) and cefotaxime (23.4%). In 45% of care episodes, the consultant recommended “no change” to the prescribed antimicrobial. The final rate of acceptance of received recommendations by the prescribing physicians was 89%. We found average decreases of 27.8% in the days of treatment per 1000 inpatient days and 22.9% in the number of antimicrobial starts per 1000 admissions in P2. The use of carbapenems, cephalosporins and glycopeptides decreased in P2 compared to P1. The average annual cost of antimicrobial treatment decreased from €150 356/year during P1 to €98 478/year in P2. ConclusionOur ASP achieved a significant decrease in the use of broad-spectrum antibiotics and antifungals. The costs associated with antimicrobial prescribing decreased following the introduction of the ASP, which was a cost-effective action in this study period.

Advanced biomaterial agent from chitosan/poloxamer 407-based thermosensitive hydrogen containing biosynthesized silver nanoparticles using Eucalyptus camaldulensis leaf extract.

The emergence of multidrug-resistant (MDR) pathogens poses a significant challenge for global public health systems, increasing hospital morbidity and mortality and prolonged hospitalization. We evaluated the antimicrobial activity of a thermosensitive hydrogel containing bio-synthesized silver nanoparticles (bio-AgNPs) based on chitosan/poloxamer 407 using a leaf extract of Eucalyptus calmadulensis. The thermosensitive hydrogel was prepared by a cold method after mixing the ingredients and left at 4°C overnight to ensure the complete solubilization of poloxamer 407. The stability of the hydrogel formulation was evaluated at room temperature for 3 months, and the absorption peak (420 nm) of the NPs remained unchanged. The hydrogel formulation demonstrated rapid gelation under physiological conditions, excellent water retention (85%), and broad-spectrum antimicrobial activity against MDR clinical isolates and ATCC strains. In this regard, minimum inhibitory concentration and minimum microbial concentration values of the bio-AgNPs ranged from 2-8 μg/mL to 8-128 μg/mL, respectively. Formulation at concentrations <64 μg/mL showed no cytotoxic effect on human-derived macrophages (THP-1 cells) with no induction of inflammation. The formulated hydrogel could be used in biomedical applications as it possesses a broad antimicrobial spectrum and anti-inflammatory properties without toxic effects on human cells.

Aortic endograft infection by Mycobacterium abscessus subsp. massiliense with acquired clarithromycin resistance: a case report

BackgroundMycobacterium abscessus subsp. massiliense (MMA) comprises a group of non-tuberculous, rapidly growing mycobacteria. Although MMA can cause pulmonary diseases, surgical site infections, and disseminated diseases, aortic endograft infection has not been reported. Here, we describe the first case of aortic endograft infection caused by MMA.Case presentationTwo months after stent-graft insertion for an abdominal aortic aneurysm, an 85-year-old man was admitted with fever and abdominal pain and was diagnosed with aortic endograft infection. Despite 14 days of meropenem and vancomycin intravenous administration, periaortic fluid pooling increased as compared to that before antibiotic administration. The abscess was drained, and fluorescent acid-fast staining of the abscess fluid revealed bacilli. We conducted genetic tests on the genes hsp65, rpoB, and sodA, performed Whole Genome Sequencing (WGS), and identified the organism as MMA. Intravenous imipenem–cilastatin (IPM/CS), amikacin (AMK), and oral clarithromycin (CAM) were administered. After 2 months, oral CAM and sitafloxacin were administered because the abscess had decreased in size. However, after 6 weeks, the abscess increased in size again. Antimicrobial susceptibility testing of the drainage fluid from the abscess resulted in the isolation of an MMA strain that had acquired resistance to CAM. Intravenous IPM/CS, AMK, and oral linezolid were added to the treatment regimen along with oral CAM and STFX. However, he was not fully cured and died 6 months later. Neither the full-length erythromycin ribosome methyltransferase (erm)(41) gene nor the rrl or rpIV gene mutations were found by Sanger sequencing in the pre- and post-treatment strains. Whole-genome sequence analysis of the post-treatment strain revealed mutations in genes with no previous reports of association with macrolide resistance.ConclusionsAortic endograft infection caused by MMA strain is extremely rare; nonetheless, MMA should be suspected as the causative microorganism when broad-spectrum antimicrobials are ineffective.

Point prevalence probing of antimicrobial prescription patterns from a developing country

ABSTRACT Background Irrational use of antibiotics intensifies resistance and jeopardizes advances made in modern medicine. We aimed to conduct a baseline gap analysis survey on antibiotic prescription practices across Pakistan. Research Design and Methods This multi-centered cross-sectional survey was conducted at six public sector tertiary care hospitals from February 2021 to March 2021. Data related to various variables including hospital infrastructure, policies and practices, monitoring and feedback, and epidemiological, clinical, and antibiotic prescription for surveyed patients was collected using World Health Organization (WHO) Point Prevalence Survey (PPS) methodology. Results In a survey of 837 inpatients, 78.5% were prescribed antibiotics. Most commonly prescribed antimicrobial was ceftriaxone (21.7%), followed by metronidazole (17.3%), cefoperazone-sulbactam (8.4%), amoxicillin-clavulanate (6.3%), and piperacillin/tazobactam (5.9%). Surgical prophylaxis (36.7%) and community-acquired infections (24.7%) were the main reasons for antibiotic prescriptions. Single antibiotics were given to 46.7% of patients, 39.9% received a combination of two antibiotics, and 12.5% were prescribed three or more antibiotics. Among six hospitals surveyed, two had drug and therapeutic committees, three had infection prevention and control committees, and one had an antibiotic formulary. Conclusion Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasize the importance of expanding antimicrobial stewardship programs among hospitals. Mentoring clinical teams could help rationalize antimicrobial use.

Pelvic Inflammatory Disease: updates from diagnosis to treatment

Pelvic inflammatory disease (PID) is a clinical syndrome caused by several microorganisms, mainly those related to sexually transmitted infections (STIs), which ascend the female genital tract towards the upper genital organs. It is a disease that affects young women, who have an active sex life and have a history of chlamydia, for example. Its clinical picture may be symptomatic, with pain in the lower abdomen being the main complaint, or in some cases the patient may be asymptomatic. The disease is confirmed by classifying the symptoms into major, minor or elaborate criteria, and by complementary laboratory and imaging tests. Its treatment can be outpatient or hospital, depending on the degree of symptoms and should be started as soon as possible, even empirically, using broad-spectrum antimicrobials. The importance of a quick diagnosis and treatment is due to the possible consequences that PID can cause, such as infertility. This literature review aims to disclose the causes and symptoms of the disease, which is one of the most important sexually transmitted infections, since the lack of a quick diagnosis and treatment, or even an inadequate treatment, increases the chances of complications for the women's health. This is a literature review on Pelvic Inflammatory Disease. A search was carried out for scientific articles in the databases Google Scholar, Scielo and indexed journals between the years 2020 to 2023, in Portuguese and English, with the following descriptors: Pelvic Inflammatory Disease, Sexually Transmitted Infections and Chlamydia trachomatis. Even though it is a condition that affects many young women, PID is an underreported disease, therefore, it is necessary to have more teaching about sex education, since the main cause of PID is STIs.

Ozonated Oil in Liposome Eyedrops Reduces the Formation of Biofilm, Selection of Antibiotic-Resistant Bacteria, and Adhesion of Bacteria to Human Corneal Cells.

The recent attention to the risk of potential permanent eye damage triggered by ocular infections has been leading to a deeper investigation of the current antimicrobials. An antimicrobial agent used in ophthalmology should possess the following characteristics: a broad antimicrobial spectrum, prompt action even in the presence of organic matter, and nontoxicity. The objective of this study is to compare the antimicrobial efficacy of widely used ophthalmic antiseptics containing povidone-iodine, chlorhexidine, and liposomes containing ozonated sunflower oil. We determined the minimum inhibitory concentration (MIC) on various microbial strains: Staphylococcus aureus (ATCC 6538), methicillin-resistant Staphylococcus aureus (ATCC 33591), Staphylococcus epidermidis (ATCC 12228), Pseudomonas aeruginosa (ATCC 9027), and Escherichia coli (ATCC 873). Furthermore, we assessed its efficacy in controlling antibiotic resistance, biofilm formation, and bacterial adhesion. All three antiseptic ophthalmic preparations showed significant anti-microbicidal and anti-biofilm activity, with the liposomes containing ozonated sunflower oil with the highest ability to control antibiotic resistance and bacteria adhesion to human corneal cells.

Examining the Veterinary Electronic Antimicrobial Prescriptions for Dogs and Cats in the Campania Region, Italy: Corrective Strategies Are Imperative.

Companion animals are increasingly being recognised as important contributors to the spread of antimicrobial-resistant bacteria. The present work aimed to measure the antimicrobial drug prescribing in dogs and cats in the Campania Region, Italy by analysing the Veterinary Electronic Prescriptions (VEPs) between 2019 and 2020. The medical records associated with antimicrobial drug prescriptions were collected according to the drug administration (systemic or topical) and the rationale for the treatment chosen. In the period under investigation, 166,879 drugs were prescribed of which 129,116 (73.4%) were antimicrobial. A total of 83,965 (65%) antibiotics were prescribed to dogs, 40,477 (31.4%) to cats, and 4674 (3.6%) to other companion animals. In dogs, 90.5% of VEPs prescribed for systemic treatment included an antimicrobial Critically Important or Highly Important or Important for human medicine (WHO, 2018). The most widely prescribed class was fluoroquinolones. The antimicrobials prescribed were mainly metronidazole-spiramycin (29.7%), amoxicillin-clavulanic (19.6%), enrofloxacin and cephalexin in dogs (16.5%) and enrofloxacin (22.6%) and amoxicillin-clavulanic acid (21.4%) in cats. Based on the results, the widespread use of broad-spectrum antimicrobials and the use of molecules for which limitations should be observed according to the EMA guidelines has emerged.

Knowing Your Target: Altered Mental Status From an Unsuspected Source

Daratumumab is a human monoclonal antibody targeting CD38 that is used in the treatment of multiple myeloma. In addition to being a target for cancer-related treatment, CD38 also plays a significant role in the immune response to infection. CD38 deficiency can increase susceptibility to several bacterial infections. This article discusses the case of a 52-year-old female with a history of IgG multiple myeloma status post autologous stem cell transplant with relapse who was receiving therapy with daratumumab, lenalidomide, and dexamethasone. She presented to the emergency department with a history of 3 to 4 days of generalized weakness, poor appetite, nausea, vomiting, watery stools, and fevers. Her symptoms did not improve with initial fluid resuscitation and broad-spectrum antimicrobials; instead, she experienced progressive neurological decline. This case illustrates how utilizing targets for cancer-directed treatments can also affect immune function, which may leave patients susceptible to unique infections that may not otherwise be commonly encountered. Therefore, advanced practitioners must understand the functional role of these targets and the sequelae that could occur when expression is altered by pharmacological therapies to allow for expeditious recognition and management.

Pharmaceuticals in hospital wastewaters: an analysis of the UBA's pharmaceutical database.

The presence of pharmaceuticals in hospital wastewaters (HWW) has been a focus of interest for researchers in the last decades. Certain therapeutic classes, such as X-ray contrast media, broad-spectrum antimicrobials and cytotoxics among others, are mainly used in hospitals-health care facilities. This study is focused on available studies monitoring the presence of pharmaceuticals in HWW around the world. To that end, the last available version (v3. 2021) of the "Pharmaceuticals in the Environment" database published by the Federal German Environment Agency (Umweltbundesamt) has been used. Almost half of all studies included (107) have been conducted in Europe. Pharmaceuticals have been monitored in HWW in 38 different countries across all five continents. The country with the greatest number of studies is Brazil (11), followed by Spain (8), China (7), and France (6). Our analysis revealed that 271 different pharmaceuticals have been detected at least once in HWW. The five drugs with more studies showing a positive detection are ciprofloxacin (38), sulfamethoxazole (36), diclofenac (34), ibuprofen (29), and trimethoprim (27). A total of 47 out of 271 drugs are considered in the NIOSH "Hazardous drug" list. However, monitoring data for some widely used drugs in hospital settings such as muscle relaxants, anesthetics, and antidotes is lacking. In conclusion, this studyprovides the first large-scale metadata analysis for the pharmaceuticals in HWW worldwide.

Acute Oral Toxicity, Haematobiochemical Parameters and Histopathological Evaluation of Povidone Iodine in Mice

Povidone-iodine is a synthetically produced topical antiseptic with a broad antimicrobial spectrum indicated for both treatment and prevention. Polidine® (a synthetic povidone-iodine solution) however, is being used by poultry farmers and some animal health practitioners with claims that it is effective against infectious bursal disease (IBD) when administered orally. And recently, research studies have shown that povidone-iodine mouthwashes, throat sprays, nasal sprays and eye drops prevent the replication and or viral loads of SARSCoV-2. Thus, this study established a safety profile of povidone-iodine. Ten adult mice were randomly assigned into 2 groups, each containing 5 mice. One of the two groups was treated with povidone-iodine orally, at a limit dose of 2,000mg/kg BW while the other group served as normal control. At the end of the study, blood samples were collected for hematological and biochemical analysis. Also, liver and kidney were harvested for both gross and histopathological examinations. Result showed the median lethal dose (LD50) of povidone-iodine was found to be &gt;2,000mg/kg BW. Significant increase (p &lt; 0.05) of total white blood cells, monocytopaenia and increased band cells were observed in the treated group when compared to the control on haematology. However, serum biochemistry revealed significant increase (p &lt; 0.01) of Aspartate aminotransferase, Alanine aminotransferase, alkaline phosphatase and Blood urea nitrogen. On histopathology, no remarkable changes in the group treated with povidone iodine were observed when compared to the control. In conclusion, this study has showed the relative safety of povidone iodine at limit dose (2,000 mg/kg BW) in mice

Design of phenothiazine-based cationic amphiphilic derivatives incorporating arginine residues: Potential membrane-active broad-spectrum antimicrobials combating pathogenic bacteria in vitro and in vivo

Multidrug-resistant bacteria infections pose an increasingly serious threat to human health, and the development of antimicrobials is far from meeting the clinical demand. It is urgent to discover and develop novel antibiotics to combat bacterial resistance. Currently, the development of membrane active antimicrobial agents is an attractive strategy to cope with antimicrobial resistance issues. In this study, the synthesis and biological evaluation of cationic amphiphilic phenothiazine-based derivatives were reported. Among them, the most promising compound 30 bearing a n-heptyl group and two arginine residues displayed potent bactericidal activity against both Gram-positive (MICs = 1.56 μg/mL) and Gram-negative bacteria (MICs = 3.125–6.25 μg/mL). Compound 30 showed low hemolysis activity (HC50 = 281.4 ± 1.6 μg/mL) and low cytotoxicity (CC50 ＞ 50 μg/mL) toward mammalian cells, as well as excellent salt resistance. Compound 30 rapidly killed bacteria by acting on the bacterial cell membrane and appeared less prone to resistance. Importantly, compound 30 showed potent in vivo efficacy in a murine model of bacterial keratitis. Hence, the results suggested compound 30 has a promising prospect as a broad-spectrum antibacterial agent for the treatment of drug-resistant bacterial infections.

Changes in Antibiotic Resistance of Acinetobacter baumannii and Pseudomonas aeruginosa Clinical Isolates in a Multi-Profile Hospital in Years 2017-2022 in Wroclaw, Poland.

In recent years, we have witnessed increasing drug resistance among bacteria, which is associated with the use and availability of an increasing number of broad-spectrum antimicrobials, as well as with their irrational and excessive use. The present study aims to analyze changes in the drug resistance of Gram-negative Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from infections in a multi-profile hospital over a five-year period (from 2017 to 2022). Among the practical results of the evaluation of these data will be the possibility to determine changes in susceptibility to the antibiotics used in the hospital. This, in turn, will help propose new therapeutic options, especially for empirical therapy, which is essential in severe infections. Analysis of the use of different antibiotic groups has made it possible to identify the causes of increasing resistance in the analyzed Gram-negative bacilli. The highest antibiotic use was observed in the hospital between 2020 and 2022, most probably due to the COVID-19 pandemic and the higher number of patients in severe condition requiring hospitalization. Unfortunately, during the period analyzed, the number of multi-resistant strains of A. baumannii was successively increasing; this seems to be related to the increased use, especially during the pandemic period, of broad-spectrum antibiotics, mainly penicillins with inhibitors, third-generation cephalosporins and carbapenems.

Anticariogenic Activity of Celastrol and Its Enhancement of Streptococcal Antagonism in Multispecies Biofilm.

Dental caries is a chronic disease resulting from dysbiosis in the oral microbiome. Antagonism of commensal Streptococcus sanguinis and Streptococcus gordonii against cariogenic Streptococcus mutans is pivotal to keep the microecological balance. However, concerns are growing on antimicrobial agents in anticaries therapy, for broad spectrum antimicrobials may have a profound impact on the oral microbial community, especially on commensals. Here, we report celastrol, extracted from Traditional Chinese Medicine's Tripterygium wilfordii (TW) plant, as a promising anticaries candidate. Our results revealed that celastrol showed antibacterial and antibiofilm activity against cariogenic bacteria S. mutans while exhibiting low cytotoxicity. By using a multispecies biofilm formed by S. mutans UA159, S. sanguinis SK36, and S. gordonii DL1, we observed that even at relatively low concentrations, celastrol reduced S. mutans proportion and thereby inhibited lactic acid production as well as water-insoluble glucan formation. We found that celastrol thwarted S. mutans outgrowth through the activation of pyruvate oxidase (SpxB) and H2O2-dependent antagonism between commensal oral streptococci and S. mutans. Our data reveal new anticaries properties of celastrol that enhance oral streptococcal antagonism, which thwarts S. mutans outgrowth, indicating its potential to maintain oral microbial balance for prospective anticaries therapy.

Identification of Candida auris by PCR and assessment of biofilm formation by crystal violet assay

IntroductionCandida auris is a notorious pathogen capable of forming biofilms on devices as well as host tissues, often culminating in infections. We evaluated characteristics of infections and the methods to diagnose C. auris over a period of three years in a tertiary care hospital. MethodsPatients admitted between 2018 and 2020, who had candidemia due to C. auris were included in the study. Identification was performed using HiCrome™ Candida Differential Agar, Vitek 2 (BioMérieux, Inc., Marcy-l’Etoile, France) and MALDI-TOF, Vitek-MS. Identification was confirmed by detection of rDNA region covering part of 5.8S, entire of ITS2, and part of 28S by polymerase chain reaction (PCR). Biofilm formation was assessed by crystal violet staining. ResultsPresence of central line and broad spectrum antimicrobials were noted in all patients whereas total parenteral nutrition was given in 82.1% of these patients. Identification by Vitek2 v8.1 correlated with MALDI-TOF MS. PCR products of length 163 ​bp were obtained in all isolates as visualized by agarose gel electrophoresis. The biofilm quantity measured as A560 of the twenty-eight C. auris isolates ranged from 0.16 to 0.80 compared to C. albicans. ConclusionsC. auris can be identified by PCR targeting specific rDNA region. Biofilm formation and quantification can be achieved by growing C. auris isolates in Mueller-Hinton broth over a duration of 48 ​h.

Emerging fungal infections of man

Many fungi are now emerging as important causes of superficial and deep seated infections of man. The indiscriminate use of broad spectrum antimicrobials by oral and topical routes and prolonged hospital stay have led to emergence of many new fungal pathogens like Candida auris, Histoplasma spp. and Emergomyces spp.. Of these, C. auris is an established nosocomial pathogen now and can colonize hospital surfaces very commonly. Immunocompromised status of the patients due to various causes like HIV infection, Diabetes mellitus and anticancer chemotherapy, have added to the problems of emerging mycoses. Other risk factors can be exposure to soil and vegetation, and aquatic animals, in case of Lobomycosis. Some of these emerging mycoses are caused by dimorphic fungi. Also, some of these pathogens are really not fungi but algae, like Prototheca spp. Many a times these fungal pathogens are very difficult to identify accurately and treat. Treatment options are limited and surgical excision may have to be tried. Some of them may not be culturable at all, and need histopathology to confirm diagnosis. Their taxonomy is also being revised and reviewed constantly. These aspects are very important and should be studied and reviewed. Here we have reviewed available information in this aspect.

In Vitro Activity of Cefiderocol Compared to Other Antimicrobials against a Collection of Metallo-Beta-Lactamase-Producing Gram-Negative Bacilli from Southern Spain.

In this study, we aimed to comparatively evaluate the in vitro activity of cefiderocol versus other antimicrobials against a well-characterized collection of metallo-beta-lactamase (MBL)-producing Gram-negative bacilli (MBL-GNB) isolates from hospitals in Andalusia, Spain. We recovered 232 MBL-GNB from Andalusian hospitals, including 160 Enterobacterales and 72 nonfermenting Gram-negative bacilli belonging to 44 different clones (2015 to 2020). Cefiderocol and comparator MICs were determined with commercial methods (UMIC [Bruker] and EUMDROXF [Sensititre; Thermo Fisher], respectively). EUCAST breakpoints were used for all antimicrobials tested, and CLSI also was used for cefiderocol. Control strains used were E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. Cefiderocol showed potent in vitro activity against isolates tested, regardless of breakpoint (susceptibility rates, 85.3% for EUCAST versus 96.6% for CLSI, P < 0.001). MIC ranges for Enterobacterales and nonfermenting Gram-negative bacilli (NF-GNB) were ≤0.03 to 1 mg/L and 0.06 to 2 (IMP), 0.06 to 8 mg/L and 0.06 to 16 (VIM), 0.25 to 16 mg/L and 2 to 16 mg/L (NDM), respectively, and 0.25 to 8 mg/L for double MBL-producing Enterobacterales. By species, all cefiderocol-susceptible rates were over 90%, except Klebsiella oxytoca, Enterobacter cloacae, Escherichia coli, and Acinetobacter spp. Significant differences were observed comparing resistant isolates between Enterobacterales and NF-GNB by EUCAST (19.4% versus 4.2%, P < 0.01), but not by CLSI (4.4% versus 1.4%, P = 0.2). Cefiderocol was the most active antimicrobial tested. Cefiderocol showed excellent in vitro activity against MBL-GNB, especially NF-GNB; almost all isolates resistant to comparators were susceptible. IMPORTANCE This article demonstrates the efficacy of cefiderocol against a large collection of well-characterized metallo-beta-lactamase-producing isolates, some of them even producing double carbapenemases. Furthermore, cefiderocol activity is compared to other novel broad-spectrum antimicrobials with activity against carbapenemases.

P36 Using the Australian National Antimicrobial Prescribing Survey portal (NAPS) to benchmark antibiotic prescribing within an Integrated Care Board (ICB): a pilot point prevalence survey (PPS) of two NHS Trusts

Abstract Background PPS is useful in evaluating volume and appropriateness of antimicrobial prescribing to guide specific antimicrobial stewardship (AMS) interventions. Integrated care systems enable collaboration within an ICB and benchmarking of antimicrobial prescribing in constituent trusts to identify disparities and learn from sharing best practice. NAPS is a web-based qualitative auditing platform which is used to conduct an annual Australia-wide PPS. To assess the suitability of NAPS in benchmarking antimicrobial prescribing practices, we piloted the NAPS platform in the acute admission ward areas in two NHS Trusts within an ICB. Methods In OUHFT, admissions to 2 acute medicine wards on a single day were extracted using the Cerner electronic prescribing system. Antimicrobial prescriptions were anonymized, reviewed using NAPS protocol and uploaded to the NAPS platform. In BHT, antimicrobial prescriptions on 2 admission wards were collected manually using the NAPS parameters and audit standards and entered directly into Excel®. Ethical approval was not required due to the anonymized nature of this audit. Results A total of 124 patients at OUHFT and 53 patients at BHT were included. The proportion of patients prescribed antimicrobials varied, with a prevalence of 23% (n = 29) at OUHFT and 54% (n = 28) at BHT. The total number of antimicrobial prescriptions was approximately 40 per trust. Compliance with guidelines for OUHFT and BHT (88% versus 83%) and stewardship appropriateness (73% versus 80%) were similar. The main indication for antimicrobials was pneumonia. The most common reasons for inappropriateness were ‘incorrect duration’ and ‘spectrum too broad’. The most prescribed antimicrobials differed, with co-amoxiclav and amoxicillin (43%) at OUHFT and metronidazole and clarithromycin (24%) at BHT. Non-compliance with guidelines was frequently associated with the use of doxycycline and co-amoxiclav (47%) at OUHFT and amoxicillin and piperacillin/tazobactam (72%) at BHT. Conclusions Benchmarking of antimicrobial prescribing was possible as both PPSs were conducted using the NAPS parameters and standards. Focusing efforts on antibiotic prescribing for pneumonia, the use of broad-spectrum antimicrobials and reducing duration of courses will be taken forward as a key focus for AMS efforts. NAPS is a suitable tool for benchmarking, sharing best practice and facilitating discussion of AMS interventions across an ICB. This model should be considered as a template for national benchmarking of antimicrobial prescribing.

Characterization of consumption and costs of antimicrobials in intensive care units in a Brazilian tertiary hospital

BackgroundThe consumption of antimicrobials and the growing resistance of infectious agents to these drugs are not related only to health issues, but also to economic parameters. ObjectivesThe study objective was to evaluate the consumption of antimicrobials in General and Covid-19 Intensive Care Units (ICUs) and the impact on institutional costs in the largest institute of a tertiary public hospital. MethodsThis is a quantitative and retrospective study, which analyzed consumption, through the Defined Daily Dose (DDD), and the annual direct cost of antimicrobials in Reais (R$) and Dollars (US$), from January to December 2021. ResultsThe total annual consumption (DDD/1000 patient-day) of antimicrobials in the ICUs was 14,368.85. β-Lactams had the highest total annual value, with a DDD/1000 patient-day of 7062.98, being meropenem the antimicrobial that reached the highest consumption (3107.20), followed by vancomycin (2322.6). Total consumption was higher in Covid-19 ICUs than in General ICUs, and the annual direct cost of antimicrobials in ICUs was US$560,680.79. ConclusionsThe study showed high consumption of broad-spectrum antimicrobials, highlighting the importance of structuring programs to manage the use of antimicrobials, both to reduce antimicrobial consumption and hospital costs, consolidating rational use even in pandemic scenarios.