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

Background: The 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. Objectives: The 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. Methods: This 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. Results: The total annual consumption (DDD/1000 patient-day) of antimicrobials in the ICUs was 14,368.85. ß-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. Conclusions: The 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.

Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity against Neisseria gonorrhoeae in preclinical studies.

INTRODUCTION: Polyphenylene carboxymethylene (PPCM) is a condensation polymer that has both contraceptive and antimicrobial activity against several sexually transmitted viruses including HIV, herpes simplex virus, Ebola virus and SARS-CoV-2 in preclinical studies. PPCM, both as an active pharmaceutical ingredient (API) and in a vaginal gel formulation (Yaso-GEL), has an excellent safety profile. Here, we evaluated the efficacy of PPCM against Neisseria gonorrhoeae in vitro and in a gonorrhoea mouse model. METHODS: The minimal inhibitory concentration (MIC) of PPCM was determined against 11 N. gonorrhoeae strains by agar dilution and a microtitre plate-based method. In vivo efficacy was tested in a murine model of N. gonorrhoeae genital tract infection by applying Yaso-GEL, PPCM incorporated in 2.7% hydroxyethylcellulose (HEC), or the HEC vehicle vaginally prior to challenge with N. gonorrhoeae. Vaginal swabs were quantitatively cultured over 5 days to assess efficacy. RESULTS: PPCM MIC against N. gonorrhoeae ranged between 5-100 µg/mL (agar dilution) and 50-200 µg/mL (microtitre plate method). PPCM/HEC gel applied vaginally prior to bacterial challenge resulted in a concentration-dependent inhibition of infection. Yaso-GEL containing 4% PPCM prevented infection in 100% of mice. Incubation of N. gonorrhoeae with PPCM increased membrane permeability, suggesting PPCM directly compromises N. gonorrhoeae viability, which may be a mechanism by which PPCM inhibits N. gonorrhoeae infection. CONCLUSIONS: Yaso-GEL containing the API PPCM showed significant activity against N. gonorrhoeae in vitro and in vivo in a female mouse model. These data support further development of Yaso-GEL as an inexpensive, non-hormonal and non-systemic product with both contraceptive and antimicrobial activity against gonorrhea and other common sexually transmitted infections (STIs). Such multipurpose prevention technology products are needed by women in all economic, social and cultural circumstances to prevent unintended pregnancy and STIs.

Antibiotic Overprescribing among Neonates and Children Hospitalized with COVID-19 in Pakistan and the Implications.

There are concerns with excessive antibiotic prescribing among patients admitted to hospital with COVID-19, increasing antimicrobial resistance (AMR). Most studies have been conducted in adults with limited data on neonates and children, including in Pakistan. A retrospective study was conducted among four referral/tertiary care hospitals, including the clinical manifestations, laboratory findings, the prevalence of bacterial co-infections or secondary bacterial infections and antibiotics prescribed among neonates and children hospitalized due to COVID-19. Among 1237 neonates and children, 511 were admitted to the COVID-19 wards and 433 were finally included in the study. The majority of admitted children were COVID-19-positive (85.9%) with severe COVID-19 (38.2%), and 37.4% were admitted to the ICU. The prevalence of bacterial co-infections or secondary bacterial infections was 3.7%; however, 85.5% were prescribed antibiotics during their hospital stay (average 1.70 ± 0.98 antibiotics per patient). Further, 54.3% were prescribed two antibiotics via the parenteral route (75.5%) for ≤5 days (57.5), with most being 'Watch' antibiotics (80.4%). Increased antibiotic prescribing was reported among patients requiring mechanical ventilation and high WBCs, CRP, D-dimer and ferritin levels (p < 0.001). Increased COVID-19 severity, length of stay and hospital setting were significantly associated with antibiotic prescribing (p < 0.001). Excessive antibiotic prescribing among hospitalized neonates and children, despite very low bacterial co-infections or secondary bacterial infections, requires urgent attention to reduce AMR.

Zinc and its impact on human health in conditions of covid-19 pandemic: What's new?.

The article is devoted to the role of the micronutrient zinc in maintaining health as well as in the formation of diseases. The data on the effect of zinc on the immune system, its participation in metabolic processes are presented, its anti-inflammatory effects and the effect on anti-infectious protection are highlighted. The reasons for the development of zinc-deficiency states, their clinical manifestations, as well as recommendations for correction are considered. On the base of modern research, the authors present the advantages of using zinc in SARS, including the prospects for its use in case of COVID-19.Copyright © 2021, Professionalnye Izdaniya. All rights reserved.

Zinc and its impact on human health in conditions of covid-19 pandemic: What's new?.

The article is devoted to the role of the micronutrient zinc in maintaining health as well as in the formation of diseases. The data on the effect of zinc on the immune system, its participation in metabolic processes are presented, its anti-inflammatory effects and the effect on anti-infectious protection are highlighted. The reasons for the development of zinc-deficiency states, their clinical manifestations, as well as recommendations for correction are considered. On the base of modern research, the authors present the advantages of using zinc in SARS, including the prospects for its use in case of COVID-19.Copyright © 2021, Professionalnye Izdaniya. All rights reserved.

Biologically Inspired: Fighting Germs Using HCIO Hydrogels with Smectites

Hypochlorous acid (HClO) is formed in the white blood cells of all mammals [1]. As part of a mechanism that developed several millions of years ago, it also helps the human body to protect against pathogens that enter it. This makes the weak acid a nature-based option for disinfection. Despite this, a disadvantage of water-thin solutions of hypochlorous acid is that they have significantly limited anti-microbial potential due to the reduced contact time. Hydrogels overcome this limitation and lead to improved and more sustainable use. Due to the high reactivity of hypochlorous acid, common additives such as polymer thickeners and natural clays are not suitable. Synthetic smectite clays -- of which the presented PURABYK-R 5500 is one example -- are very similar in structure to natural clays. However, due to their subsequent technical development, synthetic smectite clays exhibit better stability and are therefore very well suited to forming these hydrogels. They stabilize the hypochlorous acid in the required pH value range and are free from components that impair the activity of HClO. These unique additives are produced under controlled conditions from naturally occurring inorganic mineral sources. They offer the possibility of using structures from nature, paired with a very high purity and consistent quality. Their great potential is presented here using PURABYK-R 5500 as an example. [ FROM AUTHOR]

Drug News

Quicker administration may not increase use of antimicrobals... Update on cancer, cytokines, and COVID-19 vaccines... Dulaglutide efficacious in pediatric patients with type 2 diabetes... AMVUTTRA approved by FDA for polyneuropathy... Global society announces support for new bill for insulin access... [ FROM AUTHOR] Copyright of Nursing is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Knowledge and Attitudes about Antibiotics and Antibiotic Resistance of 2404 UK Healthcare Workers.

BACKGROUND: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers' (HCWs') knowledge, attitudes and behaviours towards antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented here. METHODS: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1315 respondents. RESULTS: In total, 2404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic-resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient's risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic-resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the previous week to responding to the survey due to a fear of patient deterioration or complications. CONCLUSION: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

Curbing antimicrobial resistance in post-COVID Africa: Challenges, actions and recommendations.

Background: Antimicrobial self-medication and use have significantly increased in the COVID-19 era-increasing antibiotic consumption and resulting in a high prevalence of antimicrobial resistance in Africa (AMR). We conducted a narrative review to investigate challenges associated with curbing AMR in a post-COVID-19 setting in Africa, suggesting practical measures applicable for policy-informed implementation. Method: A narrative review was performed to pinpoint AMR challenges and actions on the African continent. A comprehensive search was conducted in the scientific databases that include PubMed, PubMed Central and Google Scholar using predetermined search terms. Results: The emergence of the COVID-19 outbreak has added to the challenges of tackling AMR on the continent, which has jeopardized AMR interventions' hard-won gains. Identified challenges have been Health systems disruption, Irrational Antimicrobial Use, Weak Antimicrobials Regulatory Ecosystem, Inefficient Population Infection Prevention, and Control Practices, Inadequate access to Health Services and data challenge on AMR surveillance. Conclusion: The COVID-19 pandemic fueled AMR in Africa. There is a need for AMR control post-COVID, such as measures for ongoing antimicrobial stewardship and good infection control practices. Further, curbing AMR requires rigorous regulatory enforcement and efficient AMR Surveillance. There should be a body to raise AMR awareness among the population. Research, Innovation and Technology could play an essential role supported by capacity building and global partnership.

Impact of COVID-19 Pandemic on Antimicrobial Resistance Pattern;Transition from Resistivity to Susceptibility

Objective: The study aimed to assess the antibiotic resistance pattern before and after the pandemic to provide the physicians with general guidance for antibiotic prescribing. Material and Methods: The yearly antibiograms of different tertiary care hospitals were extracted from Pakistan Antimicrobial Resistance (AMR) Network. The data timeline observed was from January 2016 to December 2020. The data were scrutinized to the most common organism studied with the most recurring antimicrobial used. Results: Among the Gram-positive organisms, increased resistivity against penicillin was observed against both the organism, while a good susceptibility was observed against vancomycin. Among the Gram-negative organisms, the highest resistance was observed in Ceftriaxone, Ciprofloxacin, and Cotrimoxazole. Staphylococcus aureus and Escherichia coli are the most prevalent organisms in tertiary care hospitals. Conclusion: While satisfactory susceptibility was observed in Amikacin and Piperacillin/Tazobactam. The post-pandemic era resulted in a decrease in AMR due to significant changes in antibiotic prescribing patterns. This report may guide future antibiotic prescribing.

Adverse Reactions to Anti-Infective Vaccines: an Emerging Problem in the COVID-19 Era.

Purpose of review: Vaccines are an essential tool for preventing infectious diseases and reducing associated morbidity and mortality. Vaccination has a significant impact at both individual and community levels, and COVID-19 vaccination programs are a new example of the great value of this public health strategy. However, adverse reactions, especially severe reactions such as anaphylaxis, prevent these programs from progressing properly, thus limiting vaccination uptake in the population. Recent findings: The frequency of reactions and types of vaccine components, with special attention to COVID-19 vaccines studies, provides information on the magnitude and causes of adverse events. The understanding of mechanisms involved has made it possible to adequately guide diagnosis, especially to COVID-19 vaccine components, such as polyethylene glycol, trometamol, and polysorbate-80. Summary: This review focuses on adverse reactions to vaccines, with emphasis on allergic reactions. A diagnostic pathway is suggested that, on the one hand, enables to take the necessary precautions in persons with a history of allergy to vaccine components or allergic reactions to vaccines and, on the other, supports administration of subsequent doses. The overall objective is to ensure that people with allergy can be vaccinated in the same way as the rest of the population, and that they are offered alternatives where necessary.

Current status of antihistamine drugs repurposing for infectious diseases

Objectives The principal objectives of this review were to gather information on the potential role of antihistamines as anti-infective agents and to identify the gaps in research that have impaired their applicability in human health. Methods The literature search was carried using MEDLINE, PubMed and Google Scholar and included all articles in English from January 1990 to May 2022. Results The literature search identified 12 antihistamines with activity against different pathogens. Eight molecules were second-generation antihistamines with an intrinsically lower tendency to cross the blood brain barrier, thereby with fewer side effects. Only five antihistamines had in vivo evaluations in rodents, while one study utilized a wax moth model to determine astemizole's anti-Cryptococcus sp. activity when combined with fluconazole. In vitro studies showed that clemastine was active against Plasmodium, Leishmania, and Trypanosoma, while terfenadine suppressed Candida spp. and Staphylococcus aureus growth. In vitro assays found that SARS-coV-2 was inhibited by doxepin, azelastine, desloratadine, and clemastine. Different antihistamines inhibited the Ebola virus (diphenhydramine, chlorcyclizine), Hepatitis C virus (chlorcyclizine), and Influenza virus (carbinoxamine, chlorpheniramine). Generally, in vitro activity (IC50) of antihistamines was in the low to sub-µM range, except for Staphylococcus epidermidis (loratadine MIC=50 µM) and SARS-coV-2 (desloratadine 70% inhibition at 20 µM). Conclusion Many antihistamine drugs show potential to progress to clinical trials based on in vitro data and the availability of toxicological and pharmacological data. However, the eventual need to use high antihistamine doses to achieve efficacy could be an additional problem. The overall lack of systematic preclinical trials has hampered the advancement of repurposed antihistamines for off-label evaluation. The low interest of pharmaceutical companies has to be counterbalanced through collaborations between research groups, granting agencies, and the government to support the needed clinical trials.

The efficacy and safety of electrolyzed water against Covid-19 as an alternative hand sanitizer.

Aim To investigate the efficacy of electrolyzed water against viruses and its safety to the skin. Methods Virus culture was carried out at level-3 Bio-Safety (BSL3) facilities. The test material was prepared at room temperature mixed with one part virus suspension and one organic load. As an antiseptic and disinfectant control, 0.7% formaldehyde was used. Cytotoxic effects of electrolyzed water were performed on Vero cells. In order to assess the safety of electrolyzed water, a skin sensitivity test was conducted for electrolyzed water exposure. Results Electrolyzed water has a higher value of reduction factor than antiseptic and disinfectant control, formaldehyde, and it was statistically different from control. Cytotoxicity test results on Vero cells showed that electrolyzed water demonstrated safety in Vero cell viability. As many as 58 participants who met the inclusion criteria took electrolyzed water sensitivity test to the skin. The sensitivity test showed that participants with reactions to electrolyzed water were all female, with a mean age of 32.6 years. The patch-test was positive in 3 of 4 participants who reacted to the product. Conclusion Electrolyzed water is effective as a new antiseptic and disinfectant against viruses and safe for human skin.

Influence of Anti-Infective Periodontal Therapy on Subgingival Microbiota Evaluated by Chair-Side Test Compared to qPCR-A Clinical Follow-Up Study.

A chair-side test (CST) for five periodontal pathogens (Aggregatibacter actinomycetemcomitans, A.a.; Porphyromonas gingivalis, P.g.; Prevotella intermedia, P.i.; Treponema denticola, T.d.; Tannerella forsythia, T.f.) was compared with qPCR in a previous clinical study on 100 periodontitis patients at first diagnosis (T0). Following non-surgical treatment alone (SRP) or in combination with systemic or local antibiotics, 74 patients (57.4 ± 13.5 years) were again tested at the same sites from 14 to 24 months after T0. Bacterial elimination (%; compared to T0) was determined for each single species and compared between both test systems. In all patients, all five pathogens could not be fully eliminated regardless of therapy or test method. Tested with CST, the mean elimination ranged from 90% for SRP + Amoxicillin/Metronidazole to 59.13% for SRP only. The corresponding qPCR values were 30% and 29.6%. Only A.a. was eradicated in 100% by SRP + Amoxicillin/Metronidazole tested by CST, and it was 80% when qPCR was the test method. CST agreed with qPCR in 98.7% in the detection of A.a., and 74.3%, 78.4%, 73.0%, and 48.7% for P.g., P.i., T.d., and T.f., respectively. Neither conventional treatment nor the additional use of antibiotics-even with the correct indication-could completely eradicate the tested pathogens or prevent pocket reinfection.

N-chlorotaurine is highly active against respiratory viruses including SARS-CoV-2 (COVID-19) in vitro.

N-chlorotaurine (NCT) a long-lived oxidant generated by leukocytes, can be synthesized chemically and applied topically as an anti-infective to different body sites, including the lung via inhalation. Here, we demonstrate the activity of NCT against viruses causing acute respiratory tract infections, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus (RSV). Virucidal activity of NCT was tested in plaque assays, confirmed by RT-qPCR assays. Attack on virus proteins was investigated by mass spectrometry. NCT revealed broad virucidal activity against all viruses tested at 37°C and pH 7. A significant reduction in infectious particles of SARS-CoV-2 isolates from early 2020 by 1 log10 was detected after 15 min of incubation in 1% NCT. Proteinaceous material simulating body fluids enhanced this activity by transchlorination mechanisms (1 -2 log10 reduction within 1-10 min). Tested SARS-CoV-2 variants B.1.1.7 (Alpha) und B.1.351 (Beta) showed a similar susceptibility. Influenza virus infectious particles were reduced by 3 log10 (H3N2) to 5 log10 (H1N1pdm), RSV by 4 log10 within a few min. Mass spectrometry of NCT-treated SARS-CoV-2 spike protein and 3C-like protease, influenza virus haemagglutinin and neuraminidase, and RSV fusion glycoprotein disclosed multiple sites of chlorination and oxidation as the molecular mechanism of action. Application of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.

An insight into the recent developments in anti-infective potential of indole and associated hybrids.

Prevention, accurate diagnosis, and effective treatment of infections are the main challenges in the overall management of infectious diseases. The best example is the ongoing SARs-COV-2(COVID-19) pandemic; the entire world is extremely worried about at present. Interestingly, heterocyclic moieties provide an ideal scaffold on which suitable pharmacophores can be designed to construct novel drugs. Indoles are amongst the most essential class of heteroaromatics in medicinal chemistry, which are ubiquitous across natural sources. The aforesaid derivatives have become invaluable scaffolds because of their wide spectrum therapeutic applications. Therefore, many researchers are focused on the design and synthesis of indole and associated hybrids of biological relevance. Hence, in the present review, we concisely discuss the indole containing natural sources, marketed drugs, clinical candidates, and their biological activities like antibacterial, antifungal, anti-TB, antiviral, antimalarial, and anti-leishmanial activities. The structure-activity relationships study of indole derivatives is also presented for a better understanding of the identified structures. The literature data presented for the anti-infective agents herein covers largely for the last twelve years.

In vitro inactivation of SARS-CoV-2 using a povidone-iodine oral rinse.

BACKGROUND: Healthcare professionals, especially dentists and dental hygienists, are at increased risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through air-borne particles and splatter. This study assessed the in vitro virucidal activity of 0.5% (w/v) povidone-iodine (PVP-I) oral rinse against SARS-CoV-2 to demonstrate its utility as a professional oral rinse. METHODS: A 0.5% (w/v) PVP-I oral rinse formulation, placebo oral rinse, and positive (70% [v/v] ethanol and water) and negative (water) controls were assessed using the time-kill method. SARS-CoV-2 was propagated in Vero 76 host cells. Following neutralization validation, triplicate tests were performed for each test formulation and virucidal activity measured at 15, 30, and 60 s and 5 min. RESULTS: The 0.5% (w/v) PVP-I oral rinse demonstrated effective in vitro virucidal activity against SARS-CoV-2 as early as 15 s after exposure; viral titer was reduced to < 0.67 log10 50% cell culture infectious dose (CCID50)/0.1 mL (log10 reduction of > 4.0) at 30 s, whereas the placebo oral rinse reduced the SARS-CoV-2 viral titer to 4.67 and 4.5 log10 CCID50/0.1 mL at the 15- and 30-s time points, with a log10 reduction of 0.63 and 0.17, respectively. No toxicity or cytotoxic effects against Vero 76 host cells were observed with the 0.5% (w/v) PVP-I oral rinse; positive and negative controls performed as expected. CONCLUSIONS: In vitro virucidal activity of 0.5% (w/v) PVP-I oral rinse against SARS-CoV-2 was demonstrated. Rapid inactivation of SARS-CoV-2 was observed with 0.5% (w/v) formulation with a contact duration of 15 s. Clinical investigations are needed to assess the effectiveness of PVP-I oral rinse against SARS-CoV-2 in dental practice.

A review on synthetic account of 1,2,4-oxadiazoles as anti-infective agents.

Most of the currently marketed drugs consist of heterocyclic scaffolds containing nitrogen and or oxygen as heteroatoms in their structures. Several research groups have synthesized diversely substituted 1,2,4-oxadiazoles as anti-infective agents having anti-bacterial, anti-viral, anti-leishmanial, etc. activities. For the first time, the present review article will provide the coverage of synthetic account of 1,2,4-oxadiazoles as anti-infective agents along with their potential for SAR, activity potential, promising target for mode of action. The efforts have been made to provide the chemical intuitions to the reader to design new chemical entity with potential of anti-infective activity. This review will mark the impact as the valuable, comprehensive and pioneered work along with the library of synthetic strategies for the organic and medicinal chemists for further refinement of 1,2,4-oxadiazole as anti-infective agents.

Increased Use of Antibiotics in the Intensive Care Unit During Coronavirus Disease (COVID-19) Pandemic in a Brazilian Hospital.

Background: Microbial drug resistance is one of the biggest public health problems. Antibiotic consumption is an essential factor for the emergence and spread of multiresistant bacteria. Therefore, we aimed to analyze the antibiotics consumption in the Intensive Care Unit (ICU), identifying trends in the antibiotics use profile and microbiological isolates throughout the COVID-19 pandemic. Methods: We performed this retrospective observational study in intensive care units of a Brazilian tertiary hospital from January 2019 to December 2020. The primary outcome was antimicrobial consumption in the ICU, measured by defined daily doses (DDDs) per 100 bed-days. As a secondary outcome, bacterial infections (microbiological isolates) were calculated in the same fashion. Outcomes trends were analyzed using Joinpoint regression models, considering constant variance (homoscedasticity) and first-order autocorrelation assumptions. A monthly percent change (MPC) was estimated for each analyzed segment. Results: Seven thousand and nine hundred fifty-three patients had data available on prescribed and received medications and were included in the analyses. Overall, the use of antibiotics increased over time in the ICU. The reserve group (World Health Organization Classification) had an increasing trend (MPC = 7.24) from February to April 2020. The azithromycin consumption (J01FA) increased rapidly, with a MPC of 5.21 from January to April 2020. Polymyxin B showed a relevant increase from March to June 2020 (MPC = 6.93). The peak of the antibiotic consumption of Reserve group did not overlap with the peak of the pathogenic agents they are intended to treat. Conclusion: Overall antimicrobial consumption in ICU has increased in the context of the COVID-19 pandemic. The peaks in the antimicrobial's use were not associated with the rise of the pathogenic agents they intended to treat, indicating an empirical use, which is especially concerning in the context of treating multidrug-resistant (MDR) infections. This fact may contribute to the depletion of the therapeutic arsenal for MDR treatment.