Consumption of antibiotics within ambulatory care in Malta

Background: Antibiotic use is recognised as the most important driver for the development of antimicrobial resistance in community pathogens. Surveillance is therefore critical for improvement programmes. Methods: Antimicrobial distribution data for the years 2007 to 2009 were collected retrospectively by the National Antibiotic Committee from all licensed wholesale distributors (WSL) in Malta and analysed according the World Health Organization Anatomical Therapeutic Chemical classification (ATC) level 4 criteria. Results: Overall consumption increased from 18.6 defined-daily-doses/1000-inhabitant-days (DID) in 2007 to 22.7 DID in 2008 and reached 24.4 DID in 2009 - an increase of more than 30% over the three years, Penicillins with beta-lactamase inhibitor increased in volume (7.1 to 8.8 DID) but decreased in proportion (38.4% to 36.0%) between 2007 and 2009. On the other hand, second generation cephalosporins increased in both volume and proportion (2.8 to 5.4 DID; 15.0% to 22.0%). The proportion for macrolides remained stable at approximately 16% but the volume of use again increased (2.9 DID to 3.9 DID). Fluoroquinolone proportion decreased from 9.1% to 6.8%, maintaining a stable volume of use in the region of 1.7 DID. Conclusions: Antibiotic consumption in Malta has shown a consistent increasing trend over the past three years, despite a reduction in over-the-counter acquisition. Furthermore, there is evidence of a strong, and possibly unjustified, prescription of wide spectrum antibacterials. This is potentially an important driver for documented resistance in Streptococcus pneumoniae and Escherichia coli and needs to be addressed at a national level.peer-reviewe

Broad-spectrum β-lactamases among Enterobacteriaceae of animal origin: molecular aspects, mobility and impact on public health

Broad-spectrum β-lactamase genes (coding for extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases) have been frequently demonstrated in the microbiota of food-producing animals. This may pose a human health hazard since these genes may be present in zoonotic bacteria, which would cause a direct problem. They can also be present in commensals, which may act as a reservoir of resistance genes for pathogens causing disease both in humans and animals. Broad-spectrum β-lactamase genes are frequently located on mobile genetic elements, such as plasmids, transposons and integrons, which often also carry additional resistance genes. This could limit treatment options for infections caused by broad-spectrum β-lactam-resistant microorganisms. This review addresses the growing burden of broad-spectrum β-lactam resistance among Enterobacteriaceae isolated from food, companion and wild animals worldwide. To explore the human health hazard, the diversity of broad-spectrum β-lactamases among Enterobacteriaceae derived from animals is compared with respect to their presence in human bacteria. Furthermore, the possibilities of the exchange of genes encoding broad-spectrum β-lactamases – including the exchange of the transposons and plasmids that serve as vehicles for these genes – between different ecosystems (human and animal) are discussed

Characteristics of demand for antibiotics in primary care: an almost ideal demand system approach

We model demand for different classes of antibiotics used for respiratory infections in outpatient care using a linear approximate almost ideal demand system approach. We compute elasticities to socioeconomic determinants of consumption and own- and cross- price elasticities between different groups of antibiotics. We find significant elasticities between newer/more expensive generations and older/less expensive generations of antibiotics. The larger use of more expensive antibiotics is also associated with the self-dispensing status of practices, ceteris paribus.Antibiotic use, Demand equations, Demand elasticities, Almost Ideal Model, Self-dispensing

Resistance to carbapenems in non-typhoidal Salmonella enterica serovars from humans, animals and food

Non-typhoidal serovars of Salmonella enterica (NTS) are a leading cause of food-borne disease in animals and humans worldwide. Like other zoonotic bacteria, NTS have the potential to act as reservoirs and vehicles for the transmission of antimicrobial drug resistance in different settings. Of particular concern is the resistance to critical “last resort” antimicrobials, such as carbapenems. In contrast to other Enterobacteriaceae (e.g., Klebsiella pneumoniae, Escherichia coli, and Enterobacter, which are major nosocomial pathogens affecting debilitated and immunocompromised patients), carbapenem resistance is still very rare in NTS. Nevertheless, it has already been detected in isolates recovered from humans, companion animals, livestock, wild animals, and food. Five carbapenemases with major clinical importance—namely KPC (Klebsiella pneumoniae carbapenemase) (class A), IMP (imipenemase), NDM (New Delhi metallo-β-lactamase), VIM (Verona integron-encoded metallo-β-lactamase) (class B), and OXA-48 (oxacillinase, class D)—have been reported in NTS. Carbapenem resistance due to the production of extended spectrum- or AmpC β-lactamases combined with porin loss has also been detected in NTS. Horizontal gene transfer of carbapenemase-encoding genes (which are frequently located on self-transferable plasmids), together with co- and cross-selective adaptations, could have been involved in the development of carbapenem resistance by NTS. Once acquired by a zoonotic bacterium, resistance can be transmitted from humans to animals and from animals to humans through the food chain. Continuous surveillance of resistance to these “last resort” antibiotics is required to establish possible links between reservoirs and to limit the bidirectional transfer of the encoding genes between S. enterica and other commensal or pathogenic bacteria

Genetic and biochemical characterization of OXA-405, an OXA-48-Type extended-spectrum β-lactamase without significant carbapenemase activity

The epidemiology of carbapenemases worldwide is showing that OXA-48 variants are becoming the predominant carbapenemase type in Enterobacteriaceae in many countries. However, not all OXA-48 variants possess significant activity toward carbapenems (e.g., OXA-163). Two Serratia marcescens isolates with resistance either to carbapenems or to extended-spectrum cephalosporins were successively recovered from the same patient. A genomic comparison using pulsed-field gel electrophoresis and automated Rep-PCR typing identified a 97.8% similarity between the two isolates. Both strains were resistant to penicillins and first-generation cephalosporins. The first isolate was susceptible to expanded-spectrum cephalosporins, was resistant to carbapenems, and had a significant carbapenemase activity (positive Carba NP test) related to the expression of OXA-48. The second isolate was resistant to expanded-spectrum cephalosporins, was susceptible to carbapenems, and did not express a significant imipenemase activity, (negative for the Carba NP test) despite possessing a blaOXA-48-type gene. Sequencing identified a novel OXA-48-type β-lactamase, OXA-405, with a four-amino-acid deletion compared to OXA-48. The blaOXA-405 gene was located on a ca. 46-kb plasmid identical to the prototype IncL/M blaOXA-48-carrying plasmid except for a ca. 16.4-kb deletion in the tra operon, leading to the suppression of self-conjugation properties. Biochemical analysis showed that OXA-405 has clavulanic acid-inhibited activity toward expanded-spectrum activity without significant imipenemase activity. This is the first identification of a successive switch of catalytic activity in OXA-48-like β-lactamases, suggesting their plasticity. Therefore, this report suggests that the first-line screening of carbapenemase producers in Enterobacteriaceae may be based on the biochemical detection of carbapenemase activity in clinical settings

Evaluation of the Coverage of 3 Antibiotic Regimens for Neonatal Sepsis in the Hospital Setting Across Asian Countries.

Importance: High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too few isolates to meaningfully examine the expected coverage of antibiotic regimens. Objective: To assess the coverage offered by 3 antibiotic regimens for empirical treatment of neonatal sepsis in Asian countries. Design, Setting, and Participants: A decision analytical model was used to estimate coverage of 3 prespecified antibiotic regimens according to a weighted-incidence syndromic combination antibiogram. Relevant data to parameterize the models were identified from a systematic search of Ovid MEDLINE and Embase. Data from Asian countries published from 2014 onward were of interest. Only data on blood culture isolates from neonates with sepsis, bloodstream infection, or bacteremia reported from the relevant setting were included. Data analysis was performed from April 2019 to July 2019. Exposures: The prespecified regimens of interest were aminopenicillin-gentamicin, third-generation cephalosporins (cefotaxime or ceftriaxone), and meropenem. The relative incidence of different bacteria and their antimicrobial susceptibility to antibiotics relevant for determining expected concordance with these regimens were extracted. Main Outcomes and Measures: Coverage was calculated on the basis of a decision-tree model incorporating relative bacterial incidence and antimicrobial susceptibility of relevant isolates. Data on 7 bacteria most commonly reported in the included studies were used for estimating coverage, which was reported at the country level. Results: Data from 48 studies reporting on 10 countries and 8376 isolates were used. Individual countries reported 51 (Vietnam) to 6284 (India) isolates. Coverage varied considerably between countries. Meropenem was generally estimated to provide the highest coverage, ranging from 64.0% (95% credible interval [CrI], 62.6%-65.4%) in India to 90.6% (95% CrI, 86.2%-94.4%) in Cambodia, followed by aminopenicillin-gentamicin (from 35.9% [95% CrI, 27.7%-44.0%] in Indonesia to 81.0% [95% CrI, 71.1%-89.7%] in Laos) and cefotaxime or ceftriaxone (from 17.9% [95% CrI, 11.7%-24.7%] in Indonesia to 75.0% [95% CrI, 64.8%-84.1%] in Laos). Aminopenicillin-gentamicin coverage was lower than that of meropenem in all countries except Laos (81.0%; 95% CrI, 71.1%-89.7%) and Nepal (74.3%; 95% CrI, 70.3%-78.2%), where 95% CrIs for aminopenicillin-gentamicin and meropenem were overlapping. Third-generation cephalosporin coverage was lowest of the 3 regimens in all countries. The coverage difference between aminopenicillin-gentamicin and meropenem for countries with nonoverlapping 95% CrIs ranged from -15.9% in China to -52.9% in Indonesia. Conclusions and Relevance: This study's findings suggest that noncarbapenem antibiotic regimens may provide limited coverage for empirical treatment of neonatal sepsis in many Asian countries. Alternative regimens must be studied to limit carbapenem consumption

Trends and Racial/Ethnic Disparities in Antibiotic Prescribing Practices of Dentists in The United States

Objective The aim of this study was to examine trends and racial/ethnic disparities in antibiotic prescribing practices of dentists in the United States. Methods The US Medical Expenditure Panel Survey data for 1996‐2013 was analyzed. Information on patient sociodemographic characteristics, dental visits, receipt of dental procedures, and type of antibiotics prescribed following visits was obtained. Descriptive statistics were calculated separately for each year. Logistic regression analyses were conducted to identify associations during the period with and without adjustment for dental procedures and sociodemographic characteristics. Survey weights were incorporated to handle the sampling design. Results Nationally, the number of antibiotic prescribed at dental visits was estimated to be higher by 842,749 (0.4 percent) at year 2013 compared to the prescription level at 2003 were the population sociodemographic distribution kept at 2013 level. On average, the odds of prescribing antibiotics following dental care increased with each decade of study (OR: 1.10; 95% CI: [1.04, 1.17]) after adjusting for sociodemographic characteristics and receipt of dental procedures. Compared to Whites, Blacks had 21 percent (95% CI: 11%, 31%) higher odds of receiving a prescription for antibiotics from a dentist after adjusting for dental procedure and other sociodemographic characteristics. Conclusions The prescription of antibiotics following dental visits increased over time after adjustment for sociodemographic characteristics and dental procedure. The probability of being prescribed antibiotics by dentists was higher for Blacks compared to Whites

In vitro and in vivo evaluation of cephalosporins for the treatment of Lyme disease.

BackgroundLyme disease accounts for >90% of all vector-borne disease cases in the United States and affect ~300,000 persons annually in North America. Though traditional tetracycline antibiotic therapy is generally prescribed for Lyme disease, still 10%-20% of patients treated with current antibiotic therapy still show lingering symptoms.MethodsIn order to identify new drugs, we have evaluated four cephalosporins as a therapeutic alternative to commonly used antibiotics for the treatment of Lyme disease by using microdilution techniques like minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). We have determined the MIC and MBC of four drugs for three Borrelia burgdorferi s.s strains namely CA8, JLB31 and NP40. The binding studies were performed using in silico analysis.ResultsThe MIC order of the four drugs tested is cefoxitin (1.25 µM/mL) > cefamandole (2.5 µM/mL), > cefuroxime (5 µM/mL) > cefapirin (10 µM/mL). Among the drugs that are tested in this study using in vivo C3H/HeN mouse model, cefoxitin effectively kills B. burgdorferi. The in silico analysis revealed that all four cephalosporins studied binds effectively to B. burgdorferi proteins, SecA subunit penicillin-binding protein (PBP) and Outer surface protein E (OspE).ConclusionBased on the data obtained, cefoxitin has shown high efficacy killing B. burgdorferi at concentration of 1.25 µM/mL. In addition to it, cefoxitin cleared B. burgdorferi infection in C3H/HeN mice model at 20 mg/kg