High Antibiotic Consumption Research Articles

A carbapenem-focused antimicrobial stewardship programme implemented during the COVID-19 pandemic in a setting of high endemicity for multidrug-resistant Gram-negative bacteria.

Greece is among the countries characterized by high rates of antimicrobial resistance and high consumption of antibiotics, including carbapenems. To measure the impact of a carbapenem-focused antimicrobial stewardship programme (ASP) on the antibiotic consumption and patient outcomes in a Greek tertiary hospital during the COVID-19 pandemic. A quasi-experimental, before-after study, comparing a 12 month pre-intervention period with a 12 month intervention period in which a carbapenem-focused ASP was implemented. A total of 1268 patients were enrolled. The proportion of admitted patients who received carbapenems decreased from 4.1% (842 of 20 629) to 2.3% (426 of 18 245) (-1.8%; P < 0.001). A decrease of -4.9 DDD/100 patient-days (PD) (95% CI -7.3 to -2.6; P = 0.007) in carbapenem use and an increase in the use of piperacillin/tazobactam [+2.1 DDD/100 PD (95% CI 1.0-3.3; P = 0.010)] were observed. Thirty-day mortality following initiation of carbapenem treatment and all-cause in-hospital mortality remained unaltered after ASP implementation. In contrast, length of hospital stay increased (median 17.0 versus 19.0 days; P < 0.001), while the risk of infection-related readmission within 30 days of hospital discharge decreased (24.6% versus 16.8%; P = 0.007). In the post-implementation period, acceptance of the ASP intervention was associated with lower daily hazard of in-hospital death [cause-specific HR (csHR) 0.49; 95% CI 0.30-0.80], lower odds of 30 day mortality (OR 0.36; 95% CI 0.18-0.70) and higher rate of treatment success (csHR 2.45; 95% CI 1.59-3.77). Implementing and maintaining a carbapenem-focused ASP is feasible, effective and safe in settings with high rates of antimicrobial resistance, even during the COVID-19 pandemic.

Analysis of the Comparative Growth Kinetics of Paenarthrobacter ureafaciens YL1 in the Biodegradation of Sulfonamide Antibiotics Based on Substituent Structures and Substrate Toxicity

The high consumption and emission of sulfonamide antibiotics (SAs) have a considerable threat to humans and ecosystems, so there is a need to develop safer and more effective methods than conventional strategies for the optimal removal of these compounds. In this study, four SAs with different substituents, sulfadiazine (SDZ), sulfamerazine (SMR), sulfamethoxazole (SMX), and sulfamethazine (SMZ) were removed by a pure culture of Paenarthrobacter ureafaciens YL1. The effect of the initial SAs concentration on the growth rate of strain YL1 was investigated. The results showed that the strain YL1 effectively removed various SAs in the concentration range of 0.05–2.4 mmol·L−1. The Haldane model was used to perform simulations of the experimental data, and the regression coefficient of the model indicated that the model had a good predictive ability. During SAs degradation, the maximum specific growth rate of strain YL1 was ranked as SMX &gt; SDZ &gt; SMR &gt; SMZ with constants of 0.311, 0.304, 0.302, and 0.285 h−1, respectively. In addition, the biodegradation of sulfamethoxazole (SMX) with a five-membered substituent was the fastest, while the six-membered substituent of SMZ was the slowest based on the parameters of the kinetic equation. Also, density functional theory (DFT) calculations such as frontier molecular orbitals (FMOs), and molecular electrostatic potential map analysis were performed. It was evidenced that different substituents in SAs can affect the molecular orbital distribution and their stability, which led to the differences in the growth rate of strain YL1 and the degradation rate of SAs. Furthermore, the toxicity of P. ureafaciens is one of the crucial factors affecting the biodegradation rate: the more toxic the substrate and the degradation product are, the slower the microorganism grows. This study provides a theoretical basis for effective bioremediation using microorganisms in SAs-contaminated environments.

Association between antibiotic resistance and increasing ambient temperature in China: an ecological study with nationwide panel data

Antibiotic resistance leads to longer hospital stays, higher medical costs, and increased mortality. However, research into the relationship between climate change and antibiotic resistance remains inconclusive. This study aims to address the gap in the literature by exploring the association of antibiotic resistance with regional ambient temperature and its changes over time. Data were obtained from the China Antimicrobial Surveillance Network (CHINET), monitoring the prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB), Klebsiella pneumoniae (CRKP) and Pseudomonas aeruginosa (CRPA) in 28 provinces/regions over the period from 2005 to 2019. Log-linear regression models were established to determine the association between ambient temperature and antibiotic resistance after adjustment for variations in socioeconomic, health service, and environmental factors. A 1°C increase in average ambient temperature was associated with 1.14-fold increase (95%-CI [1.07-1.23]) in CRKP prevalence and 1.06-fold increase (95%-CI [1.03-1.08]) in CRPA prevalence. There was an accumulative effect of year-by-year changes in ambient temperature, with the four-year sum showing the greatest effect on antibiotic resistance. Higher prevalence of antibiotic resistance was also associated with higher antibiotic consumption, lower density of health facilities, higher density of hospital beds and higher level of corruption. Higher prevalence of antibiotic resistance is associated with increased regional ambient temperature. The development of antibiotic resistance under rising ambient temperature differs across various strains of bacteria. The National Key R&D Program of China (grant number: 2018YFA0606200), National Natural Science Foundation of China (grant number: 72074234), Fundamental Scientific Research Funds for Central Universities, P.R. China (grant number: 22qntd4201), China Medical Board (grant number: CMB-OC-19-337).

Antibiotic Stewardship und chronische Lungenerkrankungen

HintergrundDie Therapie akuter Exazerbationen von Patienten mit chronischen Lungenerkrankungen ist häufig mit der Gabe von Antibiotika vergesellschaftet. Wiederholte stationäre Aufenthalte, hohe Antibiotikaverbräuche sowie die Gefahr des Auftretens multiresistenter Keime stellen eine Belastung für das Gesundheitssystem dar.Ziel dieser ArbeitZiel dieser Arbeit ist es, einen Überblick über Antibiotic-Stewardship-Strategien für das Management von Patienten mit chronischen Lungenerkrankungen mit besonderem Fokus auf COPD („chronic obstructive pulmonary disease“) sowie Bronchiektasien und zystischer Fibrose (CF) zu geben.Material und MethodenDie Übersichtsarbeit basiert auf einer Literaturrecherche in PubMed.Ergebnisse und DiskussionPoint-of-Care-Tests (POCT) zum schnelleren Erregernachweis ergaben uneinheitliche Ergebnisse in Bezug auf die Reduktion antibiotischer Therapien. Als relativ einfaches Verfahren konnte mittels POCT C‑reaktives Protein (CRP) („cut off“ < 20 bzw. ≥ 40 mg/l) die Anwendung von Antibiotika bei Patienten mit exazerbierter COPD reduzieren, ohne die Sicherheit zu gefährden. Die Rolle von Procalcitonin bleibt unklar. Bei nichtpurulentem Sputum und einer leichten bis mittelschweren COPD-Exazerbation kann Leitliniengerecht auf eine Antibiotikatherapie verzichtet werden. Der Einsatz von Makroliden führt zu einer zunehmenden Resistenzentwicklung und birgt die Gefahr v. a. kardiovaskulärer Nebenwirkungen, sodass eine Dauertherapie bei Patienten trotz häufiger COPD-Exazerbationen kritisch gesehen werden muss. Bei der CF hat sich durch den Einsatz von CFTR(„cystic fibrosis transmembrane conductance regulator“)-Modulatoren das Management der Grunderkrankung so verbessert, dass weniger Antibiotikatherapien gebraucht wurden. Auch bei den Bronchiektasen gibt es Anlass zur Hoffnung, dass durch neue Therapien, wie z. B. Inhibitoren der neutrophilen Elastase, Antibiotika eingespart werden können. Jeder Einsatz von Antibiotika bei chronischen Lungenerkrankungen sollte leitliniengerecht erfolgen.

Current state of antimicrobial stewardship in organ transplantation in Singapore

Antibiotic stewardship programs (ASPs) are well established in the public hospitals in Singapore, but they are not mandatory for transplant programs. Given the positive impact of ASPs in non-organ transplant patients (improved use of broad-spectrum antibiotics, reduced length of stay, and lower healthcare costs), stewardship principles are likely to benefit transplant recipients. We reviewed the progress made in ASPs in the Asia Pacific region as well as the progress of our ASP over the last decade since it was established. We also described how stewardship strategies have evolved for the purposes of our transplant program. Currently, pressing stewardship issues for our transplant program include high antibiotic consumption, as well as the burden, morbidity, and mortality associated with drug-resistant bacterial infections. Transplanting the model of stewardship onto a transplant program ignores the intricacies of transplant patients; the bespoke form of stewardship, "handshake stewardship", is more appropriate. To advance the cause of ASP in the transplant unit in Singapore, stakeholder buy-in is key; empowering transplant physicians to be stewardship-focused would be more sustainable in the long run. In addition, expanding our diagnostic armamentarium, optimizing existing therapeutics and multi-disciplinary team involvement (including stakeholders from microbiology, and infection prevention teams) are vital.

Evaluation of knowledge about antibiotics and engagement with a research experience on antimicrobial resistance between pre-university and university students for five school years (2017-2021).

Antimicrobial resistance (AMR) remains a serious global health problem. Spain is the fifth country in Europe with the highest consumption of antibiotics, due in part to ignorance of the good use of these drugs and the problem of AMR. To avoid a post-antibiotic era, adequate training on this problem is key to create social awareness. This study aimed to evaluate the impact that the SWICEU project, an academic program about antibiotic discovery, has had on the knowledge of AMR and rational use of antimicrobials in pre-university students from seven schools in the province of Valencia during five academic years (2017–2021), as well as to evaluate the level of satisfaction of university and pre-university students who have participated in the project. For this study, a survey was carried out with multiple-choice questions with a single correct answer to evaluate the knowledge acquired by pre-university students before and after the project. A satisfaction survey was also designed with a Likert scale from the lowest to the highest level of satisfaction for the two groups of students after the project. Data on knowledge surveys indicated an increase in the mean number of correct answers after the sessions. In satisfaction surveys, we highlighted the issue that referred to the project’s recommendation. The data obtained confirm this project as a valuable activity, as it allows learning about AMR and the rational use of antibiotics in a pleasing and attractive way for young pre-university and university students.

Association between the Use of Antibiotics and the Development of Acute Renal Injury in Patients Hospitalized for COVID-19 in a Hospital in the Peruvian Amazon.

Introduction: A significant antibiotic prescribing pattern associated with the COVID-19 pandemic has been described. Multiple protocols included empirical antimicrobials, leading to a substantial increase in antimicrobial consumption in medical care. A higher mortality rate is described among patients diagnosed with COVID-19 who received antibiotics. Objectives: To determine the association between the use of antibiotics and the development of acute renal injury in patients infected with SARS-CoV-2 in patients treated at the Hospital II EsSalud de Ucayali, 2021. Methods: A cross-sectional-analytical study was conducted, evaluating the medical records of patients admitted to the intensive care unit between July 2020 and July 2021. For the statistical analysis, measures of central tendency and dispersion, statistical hypothesis contrast tests were used in relation to acute kidney injury (AKI), antibiotic use and associated factors, derived from linear regression models. Results: The factors that were positively associated with the development of AKI were sepsis (aPR: 2.86; 95% CI: 1.26–6.43), shock (aPR:2.49; 95% CI: 1.28–4.86), mechanical ventilation (aPR:9.11; 95% CI: 1.23–67.57), and use of vancomycin (aPR: 3.15; 95% CI: 1.19–8.27). Conclusions: In the Peruvian Amazon, there is a high consumption and inadequate prescription of antibiotics. The drugs most commonly used for the treatment of COVID-19 were: aminoglycosides, vancomycin, ivermectin, azithromycin, tocilizumab, and corticosteroids. The development of AKI among hospitalized patients was found to be related to vancomycin administration. In addition, an association was found with the use of mechanical ventilation, a high body mass index, and the presence of complications such as sepsis or shock. Therefore, inappropriate antibiotic use for COVID-19 has been associated with multiple negative outcomes and consequences.

Socio-cultural determinants of antibiotic resistance: a qualitative study of Greeks’ attitudes, perceptions and values

BackgroundAntibiotic resistance is a complex phenomenon heavily influenced by social, cultural, behavioural, and economic factors that lead to the misuse, overuse and abuse of antibiotics. Recent research has highlighted the role that norms and values can play for behaviours that contribute to resistance development, and for addressing such behaviours. Despite comparatively high antibiotic consumption in Greece, both at the community and healthcare level, Greeks have been shown to be relatively aware of the connection between antibiotic overuse and antibiotic resistance. This suggests that Greeks’ non-judicious use cannot simply be explained by lack of awareness but may relate to other factors specific to Greek society. The present study aimed to explore attitudes, perceived norms, and values in relation to antibiotics, in order to improve understanding of socio-cultural determinants of antibiotic resistance in Greece.MethodsData were collected through online focus group discussions in 2021. Twenty Greeks were recruited through purposive sampling, aiming for as heterogeneous groups as possible regarding gender (12 women, 8 men), age (range 21–55, mean 33), and education level. Interview transcripts were analysed inductively using thematic content analysis.ResultsParticipants considered antibiotic overconsumption as a consolidated habit influenced by ease of access, social expectations and, more generally, cultural practices. While critical of such norms and practices, participants opposed stewardship measures that would prioritize the societal interest in maintaining antibiotic effectiveness over individual needs. Participants considered responsibility for antibiotic resistance to be shared by the whole society, but the role of government actors and health professionals as well as of food producers was emphasized. Notably, scepticism about the prospect of effectively managing antibiotic resistance in Greece was commonly expressed.ConclusionsThe study makes explicit attitudes, perceived norms and values that, besides limited awareness, may contribute to non-judicious antibiotic use in Greece. These socio-cultural determinants of antibiotic resistance warrant further research and should be considered when designing measures aimed to mitigate this problem.

Preventive effect of methenamine in women with recurrent urinary tract infections – a case–control study

Background Urinary tract infection (UTI) is the most common bacterial infection in women. In Norwegian general practice, methenamine has been prescribed for many years as long-term prevention and accounted for 20% of the total antibiotic prescribing in 2015, as measured in defined daily dosages (DDDs). The efficacy of methenamine is unknown. If shown to be effective, this drug may become an important preventive against UTI. Objective To examine whether methenamine is preventive against recurrent UTI in women. Design Data for all antibiotics used for UTIs dispensed from all pharmacies from 2005 to 2015 were collected from the Norwegian prescription database (NorPD). Subjects Women aged ≥ 40 years with recurrent UTI, defined as ≥3 courses of UTI antibiotic/year, were included. Main outcome measures Patients using methenamine (cases) and those not using methenamine (controls) were compared. The numbers of UTI prescriptions during the 2 years before and after inclusion were analysed. Results: The yearly prevalence for recurrent UTI was 2.4% in women ≥ 40 years. The change in antibiotic use from 2 years before to 2 years after inclusion in the study differed significantly between groups: 44.6 and 34.9% reductions in the number of antibiotic prescriptions for UTI in the methenamine and control groups, respectively. The decrease in UTI antibiotic prescriptions (58.9%) was greater in patients with a higher consumption of antibiotics before starting methenamine. Conclusions Methenamine seems to be effective against recurrent UTI over the time span studied. The effect seems to be greater in patients with the highest number of recurrent UTIs. Key points Methenamine has been used for many years for prevention of recurrent UTI, but no studies have demonstrated a significant preventive effect of long time use. This study shows that methenamine seems to be effective for prevention in patients having recurrent UTI over 2 years or more. The effect seems to be larger in patients with a high number of UTIs over 2 years.

Prevalence of antibiotic resistance genes in the oral cavity and mobile genetic elements that disseminate antimicrobial resistance: A systematic review.

The objective of this review was to assess the prevalence of antibiotic resistance genes in the oral cavity and identify mobile genetic elements (MGEs) important in disseminating them. Additionally, to assess if age, geographic location, oral site, bacterial strains and oral disease influence the prevalence of these genes. Three electronic databases (Medline, Embase and the Cochrane Library) were used to search the literature. Journals and the grey literature were also hand searched. English language studies from January 2000 to November 2020 were selected. Primary screening was performed on the titles and abstracts of 1509 articles generated. One hundred and forty-seven full texts were obtained to conduct the second screening with strict inclusion and exclusion criteria. Forty-four final articles agreed with the inclusion criteria. Half of the studies were classed as low quality. tet(M) was the most prevalent gene overall and the conjugative transposon Tn916 the most common MGE associated with antibiotic resistance genes in the oral cavity. In babies delivered vaginally, tet(M) was more prevalent, whilst tet(Q) was more prevalent in those delivered by C-section. Generally, countries with higher consumption of antibiotics had higher numbers of antibiotic resistance genes. Agricultural as well as medical use of antibiotics in a country should always be considered. Between healthy, periodontitis and peri-implantitis subjects, there was no difference in the prevalence of tet(M); however, erm(B), tet(M) and tet(O) were higher in carious active children than the non-carious group. Subjects with poor oral hygiene have more pathogenic bacteria that carry resistance genes compared to those with good oral hygiene. Enterococcus faecalis isolates demonstrated significant tetracycline resistance (tet(M) up to 60% prevalence in samples) and erythromycin resistance (erm(B) up to 61.9% prevalence in samples), periodontal pathogens showed significant beta-lactam resistance with blaZ and cfxA present in up to 90%-97% of samples and the normal oral flora had a high level of erythromycin resistance with mef(A/E) present in 65% of Streptococcus salivarius isolates. The most common resistance gene was tet(M) in root canals, cfxA in subgingival plaque, erm(B) in supragingival plaque and tet(W) in 100% of whole saliva samples. The review highlights that although many studies in this area have been performed, 50% were classed as low quality. We advise the following recommendations to allow firm conclusions to be drawn from future work: the use of large sample sizes, investigate a broad range of antibiotic resistance genes, improved methodologies and reporting to improve the quality of genetic testing in microbiology and randomisation of subject selection.

Excessively Prolonged Early Antibiotic Duration in Very-Low-Birth-Weight Infants: A Multicenter Prospective Cohort Study in a Developing Country.

PurposeSignificant antibiotic overuse due to prolonged antibiotic duration has not draw enough attention in developing countries with high antibiotic consumption. We aimed to describe the current status of prolonged early antibiotic duration in very-low-birth-weight (VLBW) infants in a large regional multicenter cohort in China.Patients and MethodsInstitution-based prospective cohort study was conducted in all VLBW infants admitted to 16 Grade A tertiary hospitals between January 1, 2019 and December 31, 2020. Early antibiotic use was defined as antibiotic initiation within the first 3 days of life. Prolonged early antibiotic course was defined as early antibiotic initiation for more than 7 days in infants with early-onset sepsis (EOS) or more than 3 days in infants with unlikely EOS. Antibiotic use was described as days of therapy (DOT) per 1000 patient days (PD).ResultsAmong 1684 eligible VLBW infants, 1544 (91.7%) infants were prescribed with prolonged early antibiotic course, including 618 infants with EOS and 926 infants with unlikely EOS. The median duration of early antibiotic course was 13 (IQR 8;20) days, with 78.0% of courses >7 days and 43.6% of courses >14 days. Total early antibiotic use was 408.3DOT/1000Pd, of which prolonged antibiotic courses accounted for 98.2% of all antibiotic use days. More than three antibiotics used, escalation antibiotic therapy, antibiotics for special use and the use of third generation cephalosporins and carbapenems were significantly common in prolonged courses compared to short courses in both infants with EOS and unlikely EOS group (P<0.05).ConclusionA large proportion of VLBW infants had excessively prolonged early antibiotic durations in the regional multicenter in China. Timely discontinuation of antibiotics in VLBW infants according to standardized guidelines and limit on the use of third-generation cephalosporins and carbapenems may be key drivers in reducing the antibiotic overuse in developing countries like ours.

Perspectives of physicians and pharmacists on rational use of antibiotics in Turkey and among Turkish migrants in Germany, Sweden and the Netherlands: a qualitative study

BackgroundAntimicrobial resistance may result from inappropriate use of antibiotics in health care. Turkey is one of the countries with the highest antibiotic consumption in the world. Considering the role of transnational ties between Turkish migrants and their social contacts in Turkey, the attitudes and behaviors relating to rational antibiotic use in Turkey can also affect the use of antibiotics by Turkish migrants residing abroad. This study explores physicians’ and pharmacists’ experiences and perspectives on rational antibiotic use among Turkish adults in Turkey and among Turkish migrants in Germany, Sweden, and the Netherlands, three European countries with large populations of Turkish migrants.MethodsFollowing a qualitative study design using convenience and snowball sampling, in-depth interviews with 21 family physicians and 24 pharmacists were conducted in the aforementioned countries. We transcribed all interviews verbatim and performed content analysis separately in the countries, followed by translation, pooling and joint interpretation of the findings.ResultsPhysicians and pharmacists encountered irrational use of antibiotics among their patients in Turkey. Physicians interviewed in the three European countries explained that Turkish migrants differ from non-migrants with respect to their attitudes towards antibiotics, for example by more often expecting to be prescribed antibiotics. All physicians and pharmacists in the selected countries reported to inform their patients on how to use antibiotics upon prescription; however, Turkish migrants’ poor language proficiency was considered as a substantial communication barrier by the physicians and pharmacists interviewed in the European countries.ConclusionsThe study illustrated some aspects of irrational antibiotic use among the population in Turkey and Turkish migrants in selected European countries. It emphasized the need for closer community participation, adequate information campaigns, as well as in-service training of health care providers in Turkey. The strategies and interventions on rational antibiotic use should also be supported and encouraged by health care providers, who need to reach out to people with various cultural backgrounds.

Co-infections and antimicrobial use among hospitalized COVID-19 patients in Punjab, Pakistan: findings from a multicenter, point prevalence survey

ABSTRACT There are reports of high rates of antibiotic prescribing among hospitalized patients with COVID-19 around the world. To date, however, there are few reports of prescribing in relation to COVID-19 in Pakistan. Herein, we describe a point prevalence survey of antibiotic prescribing amongst patients hospitalized with suspected or proven COVID-19 in Pakistan. A Point Prevalence Survey (PPS) was undertaken in seven tertiary care health facilities in Punjab Provence, Pakistan. Baseline information about antimicrobial use according to the World Health Organization (WHO) standardized methodology was collected on a single day between 5th and 30 April 2021. A total of 617 patients’ records were reviewed and 578 (97.3%) were documented to be receiving an antibiotic on the day of the survey. The majority (84.9%) were COVID-19 PCR positive, 61.1% were male and 34.9% were age 36 to 44 years. One quarter presented with severe disease, and cardiovascular disease was the major comorbidity in 13%. Secondary bacterial infection or co-infection (bacterial infection concurrent with COVID-19) was identified in only 1.4%. On the day of the survey, a mean of 1.7 antibiotics was prescribed per patient and 85.4% antibiotics were recorded as being prescribed for ‘prophylaxis’. The most frequently prescribed antibiotics were azithromycin (35.6%), ceftriaxone (32.9%) and meropenem (7.6%). The majority (96.3%) of the antibiotics were empirical and all were from WHO Watch or Reserve categories. Overall, a very high consumption of antibiotics in patients hospitalized with suspected or proven COVID-19 was observed in Pakistan and this is concerning in view of already high rates of antimicrobial resistance in the region. Antimicrobial stewardship programs need to urgently address unnecessary prescribing in the context of COVID-19 infection.

Modulating Gut Microbiota: An Emerging Approach in the Prevention and Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive neuromuscular disorder characterized by demyelination of neurons of the central nervous system (CNS). The pathogenesis of the disorder is described as an autoimmune attack targeting the myelin sheath of nerve cell axons in the CNS. Available treatments only reduce the risk of relapse, prolonging the remissions of neurological symptoms and halt the progression of the disorder. Among the new ways of targeting neurological disorders, including MS, there is modulation of gut microbiota since the link between gut microbiota has been rethought within the term gut-brain axis. Gut microbiota is known to help the body with essential functions such as vitamin production and positive regulation of immune, inflammatory, and metabolic pathways. High consumption of saturated fatty acids, gluten, salt, alcohol, artificial sweeteners, or antibiotics is the responsible factor for causing gut dysbiosis. The latter can lead to dysregulation of immune and inflammatory pathways, which eventually results in leaky gut syndrome, systemic inflammation, autoimmune reactions, and increased susceptibility to infections. In modern medicine, scientists have mostly focused on the modulation of gut microbiota in the development of novel and effective therapeutic strategies for numerous disorders, with probiotics and prebiotics being the most widely studied in this regard. Several pieces of evidence from preclinical and clinical studies have supported the positive impact of probiotic and/or prebiotic intake on gut microbiota and MS. This review aims to link gut dysbiosis with the development/progression of MS, and the potential of modulation of gut microbiota in the therapeutics of the disease.

Evaluation of more than one billion outpatient prescriptions and eight-year trend showing a remarkable reduction in antibiotic prescription in Turkey: A success model of governmental interventions at national level.

To present the antibiotic prescription trend between 2011-2018 at primary healthcare in Turkey in order to evaluate the effects of interventions at national level for providing rational prescription of antibiotics. Electronic prescription data of the family physicians collected from January 1, 2011 to December 31, 2018 in 81 provinces of Turkey were recorded through the Prescription Information System and screened for the antimicrobial drugs. The interventions to promote rational antibiotic use during 2011-2018 in Turkey includes reminding the legislation to stop access of antibiotics without prescription, monitoring of antibiotic prescription behaviors of primary healthcare physicians, and education of healthcare workers and the public on the appropriate use of antibiotics. A total of 1 054 261 396 prescriptions for outpatients of all age groups were recorded during this period. Of the prescriptions written by family physcians, 34.94% were containing at least one antibiotic in 2011, which declined to 24.55% in 2018. Antibiotics constituted 13.99% of all the items in prescriptions in 2011 and 10.47% in 2018. Percentage of total antibiotic expenditure to the total drug expanditure decreased from 14.14% to 4.12% during 2011-2018. The most commonly prescribed antibiotics were amoxicillin and enzyme inhibitor combination, cefdinir, and cefuroxime during 2011-2018, with an increasing trend for prescription of first-line antibiotic, amoxicillin, in recent years. Governmental interventions at national level have contributed to reducing antibiotic prescription and increasing preference of first-line antibiotics at primary healthcare level in Turkey over a course of 8 years. Turkey's model of governmental interventions may set an example for other countries with high consumption of antibiotics, and contribute to the actions against antimicrobial resistance worldwide.

Rational use of antimicrobials during COVID-19 times in Peru: role of antimicrobial stewardship programs and interventions in terms of infection control

Antimicrobial resistance (AMR) is an additional slow-evolving pandemic that precedes the COVID-19 pandemic and will continue when it ends. However, in countries such as Peru where there is high consumption and inadequate prescription of antibiotics, a more challenging future scenario can be expected. Antimicrobial Stewardship Programs (ASP) are multidisciplinary teams of professionals that aim to contain the emergence of multidrug-resistant organisms through strategies such as audit of antibiotic prescription or creating antibiotic treatment guidelines based on local AMR rates. The difficulty in the timely diagnosis of co-infections or superinfections in the clinical course of COVID-19 leads to inappropriate use of antibiotics, forcing ASP to adapt their strategies in this changing scenario. In Latin America, ASP not only has to promote behavior change in antibiotic prescribers but also fight the epidemic of false information (infodemia) and disinformation campaigns on COVID-19. Furthermore, poor-quality infection prevention and control principles require evaluating strategies to mitigate the subsequent impact on the AMR.

Epidemiology of Multidrug-Resistant Pseudomonas aeruginosa in the Middle East and North Africa Region.

ABSTRACTOver the last decades, there has been a dramatic global increase in multidrug-resistant (MDR) pathogens particularly among Gram-negative bacteria (GNB). Pseudomonas aeruginosa is responsible for various health care-associated infections, while MDR P. aeruginosa causes significant morbidity and mortality. Middle East and North Africa (MENA) represent an unexplored geographical region for the study of drug resistance since many of these countries are at crossroads of high volume of travel, diverse expatriate populations, as well as high antibiotic consumption despite attempts to implement antimicrobial stewardship programs. This minireview analyzes epidemiology, microbiological, and genomic characteristics of MDR P. aeruginosa in the MENA region. Published data on MDR P. aeruginosa prevalence, antimicrobial resistance patterns, and genetic profiles from studies published during the past 10 years from 19 MENA countries have been included in this minireview. There is wide variation in the epidemiology of MDR P. aeruginosa in the MENA region in terms of prevalence, antimicrobial characteristics, as well as genetic profiles. Overall, there is high prevalence of MDR P. aeruginosa seen in the majority of the countries in the MENA region with similarities between neighboring countries, which might reflect comparable population and antibiotic-prescribing cultures. Isolates from critical care units are significantly resistant particularly from certain countries such as Saudi Arabia, Egypt, Libya, Syria, and Lebanon with high-level resistance to cephalosporins, carbapenems, and aminoglycosides. Colistin susceptibility patterns remains high apart from countries with high-level antibiotic resistance such as Saudi Arabia, Syria, and Egypt.

Evaluation of Adult Outpatient Antibiotics Use at Jimma Medical Center (with Defined Daily Doses for Usage Metrics).

IntroductionInappropriate antibiotic use is a major public health concern and driver of antibiotic resistance. Excessive exposure to antibiotics results in the emergence and spread of drug-resistant microorganisms. This study aimed to measure the volume of antibiotic consumption at the outpatient settings in a tertiary-care teaching hospital in Ethiopia.MethodsA cross-sectional study was undertaken from February 01, 2019 to March 31, 2019 at Jimma Medical Center in southwest Ethiopia. Antibiotics use was analyzed using Anatomical Therapeutic Chemical Classification and Defined Daily Dose (DDD) system. Antibiotic use was calculated as DDD per 100 outpatients per day. Antibiotics were classified based on World Health Organization “AWaRe” classification scheme as “Access”, “Watch” and “Reserve” group antibiotics and measured their consumption intensity.ResultsA total of 496 adult patients were included in the study. The mean (SD) age of participants was 33.07 (14.05) years. The total amount of antibiotics consumed was 5.31 DDD/100 outpatients per day. Ciprofloxacin was the most commonly [122 (21.12%)] prescribed antibiotics with DDD/100 outpatients per day value of 1.13, followed by amoxicillin [68 (11.76%)] with DDD/100 outpatients per day value of 0.44, and azithromycin [61 (10.55%)] with DDD/100 outpatients per day value of 0.51. On antibiotic consumption index, antibiotics in the “Watch” group had 2.10 DDD/100 outpatients per day.ConclusionThere was high consumption of antibiotics in the study setting. Based on the use control criteria, half of the antibiotics used were in the “Watch” group. The high level of consumptions of antibiotics, such as ciprofloxacin, norfloxacin, and azithromycin, in particular, requires further scrutiny and calls for an urgent implementation of an antibiotic stewardship program at the hospital.

Doctors' Perceptions, Attitudes and Practices towards the Management of Multidrug-Resistant Organism Infections after the Implementation of an Antimicrobial Stewardship Programme during the COVID-19 Pandemic.

Background: Greece is among the European countries with the highest consumption of antibiotics, both in community and hospital settings, including last-line antibiotics, such as carbapenems. We sought to explore doctors’ perceptions, attitudes and practices towards the management of patients with multidrug-resistant organism (MDRO) infections after the implementation of an antimicrobial stewardship programme (ASP) in a tertiary academic hospital during the COVID-19 pandemic. Methods: A self-administered, internet-based questionnaire survey was completed by doctors of the University Hospital of Heraklion in Crete, Greece. Results: In total, 202 (59.1%) hospital doctors fully completed the questionnaire. Most of them agreed that the prospective audit and feedback ASP strategy is more effective and educational than the preauthorization ASP strategy. ASP implementation prompted most respondents to monitor the continuously evolving microbiological data of their patients more closely and affected them towards a multidisciplinary and personalised care of patients with infections caused by MDROs and towards a more rigorous implementation of infection prevention and control measures. The vast majority of participants (98.5%) stated that ASP must be continued and further developed during the COVID-19 pandemic. Conclusion: The ASP implementation in our hospital had a beneficial impact on doctors’ perceptions, attitudes and practices with regard to the management of infections due to MDROs.

High global consumption of potentially inappropriate fixed dose combination antibiotics: Analysis of data from 75 countries.

Antibiotic fixed dose combinations (FDCs) can have clinical advantages such as improving effectiveness and adherence to therapy. However, high use of potentially inappropriate FDCs has been reported, with implications for antimicrobial resistance (AMR) and toxicity. We used a pharmaceutical database, IQVIA-Multinational Integrated Data Analysis System (IQVIA-MIDAS®), to estimate sales of antibiotic FDCs from 75 countries in 2015. Antibiotic consumption was estimated using standard units (SU), defined by IQVIA as a single tablet, capsule, ampoule, vial or 5ml oral suspension. For each FDC antibiotic, the approval status was assessed by either registration with the United States Food and Drug Administration (US FDA) or inclusion on the World Health Organization (WHO) Essential Medicines List (EML). A total of 119 antibiotic FDCs were identified, contributing 16.7 x 109 SU, equalling 22% of total antibiotic consumption in 2015. The most sold antibiotic FDCs were amoxicillin-clavulanic acid followed by trimethoprim/sulfamethoxazole and ampicillin/cloxacillin. The category with the highest consumption volume was aminopenicillin/β-lactamase inhibitor +/- other agents. The majority of antibiotic FDCs (92%; 110/119) were not approved by the US FDA. Of these, the most sold were ampicillin/cloxacillin, cefixime/ofloxacin and metronidazole/spiramycin. More than 80% (98/119) of FDC antibiotics were not compatible with the 2017 WHO EML. The countries with the highest numbers of FDC antibiotics were India (80/119), China (25/119) and Vietnam (19/119). There is high consumption of FDC antibiotics globally, particularly in middle-income countries. The majority of FDC antibiotic were not approved by either US FDA or WHO EML. International initiatives such as clear guidance from the WHO EML on which FDCs are not appropriate may help to regulate the manufacturing and sales of these antibiotics.