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Increasing use of antibiotics and rising levels of bacterial resistance to antibiotics are a challenge to global health and development. Successful initiatives for containing the problem need to be communicated and disseminated. In Sweden, a rapid spread of resistant pneumococci in the southern part of the country triggered the formation of the Swedish strategic programme against antibiotic resistance, also known as Strama, in 1995. The creation of the programme was an important starting point for long-term coordinated efforts to tackle antibiotic resistance in the country. This paper describes the main strategies of the programme: committed work at the local and national levels; monitoring of antibiotic use for informed decision-making; a national target for antibiotic prescriptions; surveillance of antibiotic resistance for local, national and global action; tracking resistance trends; infection control to limit spread of resistance; and communication to raise awareness for action and behavioural change. A key element for achieving long-term changes has been the bottom-up approach, including working closely with prescribers at the local level. The work described here and the lessons learnt could inform countries implementing their own national action plans against antibiotic resistance.

IntroductionThere is controversy regarding the importance of air-transmitted infections for surgical site infections (SSIs) after orthopaedic surgery. Research has been hindered by both the inability in blinding the exposure, and by the need for recruiting large enough cohorts. The aim of this study is to investigate whether using a new form of air purifier using plasma air purification (PAP) in operating rooms (ORs) lowers the SSI rate or not.Methods and analysisMulticentre, double-blind, cluster-randomised, placebo-controlled trial conducted at seven hospitals in 2017–2022. All patients that undergo orthopaedic surgery for minimum 30 min are included. Intervention group: patients operated in OR with PAP devices turned on. Control group: patients operated in OR with PAP devices turned off. Randomisation: each OR will be randomised in periods of 4 weeks, 6 weeks or 8 weeks to either have the devices on or off. Primary outcome: any SSI postoperatively defined as a composite endpoint of any of the following: use of isoxazolylpenicillin, clindamycin or rifampicin for 2 days or more, International Classification of Diseases codes or Nordic Medico-Statistical Committee codes indicating postoperative infection. In a second step, we will perform a chart review on those patients with positive indicators of SSI to further validate the outcome. Secondary outcomes are described in the Methods section. Power: we assume an SSI rate of 2%, an SSI reduction rate of 25% and we need approximately 45 000 patients to attain a power of 80% at a significance level of 0.05.Ethics and disseminationThe study is approved by the Swedish Ethical Review Authority. The interim analysis results from the study will be presented only to the researchers involved unless the study thereafter is interrupted for whatever reason. Publication in a medical journal will be presented after inclusion of the last patient.Trial registration numberNCT02695368.

Beta-lactam antibiotics are active against many gram-negative, gram-positive and anaerobic organisms. Care must be taken when selecting a specific drug because each beta-lactam group has a somewhat different antimicrobial spectrum.

Background Prescribing in dental practice has a relatively small but important contribution to the quantity of antibiotics prescribed in primary care. This study aimed to analyse antibiotic prescribing in dentistry over time (2010–2016) in 4 different Northern European countries and their relative contribution to national outpatients consumption. Methods This retrospective study evaluated the frequency and number of national antibiotic prescriptions written by dentists in England, Scotland, Norway and Sweden. The consumption of such antibiotics was measured using WHO defined daily doses (DDDs), DDDs per 100,000 inhabitants per day (DIDs 100,000 ). Results A total of more than 27 million prescriptions (27,026,599) archived between 2010 and 2016 from the four countries were analysed. The national contribution of Norwegian dentists to the total primary care prescription during this period was 8%. The corresponding figures for Sweden, Scotland and England were 7, 6, and 8%. Dental contribution to National antibiotic use in all four countries has decreased over the study time period for commonly prescribed antibiotics in dentistry, i.e., the beta-lactams (Phenoxymethyl penicillin/Amoxicillin) and metronidazole. There were less numbers of prescriptions by dentists in Norway and Sweden compared to England and Scotland. Marked differences in some classes of antibiotics were noted with Phenoxymethyl penicillin dominating in Sweden/Norway compared to Amoxicillin and Metronidazole in England/Scotland. In England and Scotland, dentists were the largest prescribers of metronidazole in primary care. Clindamycin prescriptions was higher in Norway and Sweden. Conclusion Noticeable differences exist in prescribing patterns for the management of oral infections. High levels of metronidazole use in England and Scotland also require further analysis. All countries over the study period showed a decrease in total numbers of antibiotics prescribed.

The preparation and characterization of ionic liquids and organic salts (OSILs) that contain anionic penicillin G [secoPen] and amoxicillin [seco-Amx] hydrolysate derivatives and their in vitro antibacterial activity against sensitive and resistant Escherichia coli and Staphylococcus aureus strains is reported. Eleven hydrolyzed β-lactam-OSILs were obtained after precipitation in moderate-to-high yields via the neutralization of the basic ammonia buffer of antibiotics with different cation hydroxide salts. The obtained minimum inhibitory concentration (MIC) data of the prepared compounds showed a relative decrease of the inhibitory concentrations (RDIC) in the order of 100 in the case of [C2OHMIM][seco-Pen] against sensitive S. aureus ATCC25923 and, most strikingly, higher than 1000 with [C16Pyr][seco-Amx] against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. These outstanding in vitro results showcase that a straightforward transformation of standard antibiotics into hydrolyzed organic salts can dramatically change the pharmaceutical activity of a drug, including giving rise to potent formulations of antibiotics against deadly bacteria strains.

Background: Allergy to penicillins remains an important issue. Penicillin skin testing (PST) with major and minor determinants has been shown to be a highly valuable tool for identifying IgE-mediated penicillin allergy. The value of additional testing with side-chain-specific moieties from semisynthetic penicillins such as amoxicillin is not well-established in spite of the widespread use of these medications. Methods: A retrospective review of all consecutive inpatient PST results from 1995 to 2007 comprising 1,068 patients was performed in our institution on individuals with a self-reported history of beta-lactam allergy to assess the importance of including the amoxicillin determinant in a previously validated PST panel. Descriptive statistics were performed. The PST panel included penicilloyl-polylysine, penicillin G, penicilloate, penilloate and amoxicillin. Results: Of 1,068 patients, 243 (23%) had a positive skin test reaction on the PST panel. Testing with amoxicillin was positive in 30.9% of patients, the majority of whom (81%) were also positive to 1 or more standard penicillin reagents. Fourteen of the 243 positive patients (5.8%) had a positive skin test reaction only to amoxicillin. Additionally, the use of penicilloate and penilloate minor determinants in combination with penicillin G identified a greater percentage of penicillin-allergic individuals compared to using only penicillin G (22.6 vs. 6.6%), demonstrating their importance in the PST panel. Conclusions: These data indicate that the inclusion of the amoxicillin determinant appears to identify a small but important group of allergic individuals who may otherwise test negative on a PST panel.

It was hypothesized that treatment of clinical mastitis with a combination of a nonsteroidal antiinflammatory treatment (meloxicam) and a parenteral antibiotic (penethamate hydriodide) would result in lower somatic cell counts (SCC), reduced milk yield losses, improved clinical outcomes, and reduced culling rates compared with antibiotic therapy alone. Cows in 15 herds with clinical mastitis during the first 200 d of lactation (median = 13 d) were treated with 5g of penethamate hydriodide daily for 3 d, and one-half these cows were treated with 250mg of the nonsteroidal antiinflammatory drug meloxicam (n = 361 cows), whereas the other half (n = 366 cows) were treated with the vehicle (control group). Milk samples for bacteriology were collected from clinically affected glands before treatment, and samples were collected at 7 (±3), 14 (±3), and 21 (±3) d after commencement of treatment for SCC determination. Additionally, the rectal temperature, udder edema score, California Mastitis Test score, and milk clot score were determined before treatment and daily milk yield data were collected across the lactation. There were no differences between the treatment groups in calving date, days in milk, age, breed, rectal temperature, California Mastitis Test score, clot score, udder edema score, or bacterial pathogens isolated before treatment. There was no difference between treatment groups in the number of cows that were defined as treatment failures (i.e., re-treated within 24 d of initial treatment, died, or the treated gland stopped producing milk); 79 (21.9%) vs. 92 (25.1%) cows in the meloxicam and control groups failed, respectively. The SCC was lower in the meloxicam-treated group compared with the control group after treatment [550±48 vs. 711±62 geometric mean (×1,000/mL)±standard error of the mean SCC for quarters after treatment with meloxicam vs. control, respectively]. There was no difference in milk yield for the cows treated with meloxicam compared with the control cows within 28 or 200 d after treatment. Fewer meloxicam-treated than control cows were removed (culled) from the herds [39/237 (16.4%) vs. 67/237 (28.2%) for meloxicam vs. control cows, respectively; odds ratio = 0.42, 95% confidence interval = 0.26 to 0.68]. It was concluded that treatment of cows with clinical mastitis with a combination of meloxicam and penethamate resulted in a lower SCC and a reduced risk of removal from the herd (culling) compared with treatment with penethamate alone.

The manufacturing of PrePen (benzylpenicilloyl-polylysine) was suspended from September 2000 through November 2001 because of Food and Drug Administration intervention. PrePen is penicilloyl bound to polylysine and is considered to be the major determinant of penicillin metabolism; it is used as a skin-testing reagent to detect immunoglobulin E antibodies in people with a history of penicillin allergy. Because of the uncertainty of whether PrePen would be made available in the future, we attempted to make benzylpenicilloyl-polylysine in our laboratory using a modification of a previously described method. Subsequently, we compared our preparation with PrePen by enzyme-linked immunosorbent assay and skin testing. Using a patient previously documented to have a positive reaction to PrePen by history and intradermal skin testing, a puncture test to PrePen as well as dilutions of benzylpenicilloyl-polylysine was negative. Positive intradermal tests were performed on PrePen and benzylpenicilloyl-polylysine at 5 mg/mL. The enzyme-linked immunosorbent assay was performed to compare the antigenicity of PrePen and benzylpenicilloyl-polylysine and revealed similar binding to both. Subsequently, cutaneous testing on 10 additional penicillin-allergic people was performed, with corroborative results. Our benzylpenicilloyl-polylysine production methodology could prove useful to those who do not have access to PrePen or another similar reagent.

The objective of this study was to compare the clinical and bacteriological cure rates of cows with clinical mastitis following treatment with either tylosin base (5g injected 3 times at 24-h intervals; n = 306) or penethamate hydriodide (5g injected 3 times at 24-h intervals; n = 289). Duplicate milk samples were collected before treatment and again 14±3 and 21±3 d later for microbiological analysis. Only those quarters from which gram-positive mastitis pathogens were isolated before treatment were included in the analyses. Streptococcus uberis was the most prevalent isolate. The number of cows with clinical failure (i.e., retreated within 21 d of enrollment) did not differ between treatments (64 vs. 63, respectively). At the quarter level, there was no difference in the proportion of bacteriological cure between treatments (81.2 vs. 83.8% for penethamate hydriodide or tylosin, respectively). The proportions of clinical and bacteriological cure were influenced by age, herd, severity of mastitis, number of glands within the cow with clinical mastitis, bacterial species, and days postpartum at enrollment. There was no difference between treatment groups for SCC (4.46 vs. 4.44±0.08, mean±standard error of the difference in ln SCC for cows treated with penethamate hydriodide or tylosin, respectively) or production of milk solids (1.45 vs. 1.48±0.02 kg/d of milk fat + protein, for the penethamate hydriodide or tylosin treatment, respectively). Overall, there was no difference in the proportions of clinical failure (17.3 vs. 16.5% of cows treated with penethamate hydriodide or tylosin, respectively) or bacteriological cure (79.8 vs. 82.0% of cows treated with penethamate hydriodide or tylosin, respectively), or in SCC or milk production between dairy cows with clinical mastitis and those treated for clinical mastitis with 1 of 2 parenteral antibiotic therapies.

Deacetoxy/deacetylcephalosporin C synthase (acDAOC/DACS) from Acremonium chrysogenum is a bifunctional enzyme that catalyzes both the ring-expansion of penicillin N to deacetoxycephalosporin C and the hydroxylation of the latter to deacetylcephalosporin C. The R308 residue located in close proximity to the C-terminus of acDAOC/DACS was mutated to the other 19 amino acids. In the resulting mutant pool, R308L, R308I, R308T and R308V showed significant improvement in their ability to convert penicillin analogs, thus confirming the role of R308 in controlling substrate selectivity, the four amino acids all possess short aliphatic sidechains that may improve hydrophobic interactions with the substrates. The mutant R308I showed the highest reactivity for penicillin G, with 3-fold increase in kcat/Km ratio and 7-fold increase in relative activity.