Adherence to antibiotic guidelines in the treatment of acute pharyngeal infections.

INTRODUCTION: We aimed to investigate doctors' ad-herence to the local antibiotic guidelines for treatment of patients admitted with acute pharyngeal infections and to identify patient-related risk factors for non-adherence. METHODS: All patients with acute tonsillitis, peritonsillar abscess (PTA), and parapharyngeal abscess admitted to the Ear-Nose-Throat Department, Aarhus University Hospital, in the 2001-2014 period were included in the study. RESULTS: In total, 2,567 patients were hospitalised with acute pharyngeal infection. In non-allergic patients, penicillin was prescribed to 81%, either alone (48%) or in combination with metronidazole (33%). Macrolides (54%) and cefuroxime (44%) were the drugs of choice in 85 (98%) patients who were allergic to penicillin. Patients were prescribed antibiotics according to guidelines in 63% of cases. The addition of metronidazole to penicillin was the main (75% of cases) reason for non-adherence. Increasing patient age and male gender were independent risk factors for non-adherence. PTA patients treated according to the guidelines had a significantly shorter hospital stay than patients treated with additional metronidazole or broad-spectrum antibiotics. CONCLUSIONS: A significant (37%) proportion of patients with acute pharyngeal infections were treated non-adherently to antibiotic guidelines, mainly because of (inappropriate) addition of metronidazole to penicillin. FUNDING: This work was supported by the Lundbeck Foundation (Grant number R185-2014-2482). TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency.

Historical and Hygienic Aspects on Roles of Quality Requirements for Antibiotic Products in Japan : Part 3-Introduction of Technology and Knowledge in the Production Process and Quality Control of Penicillin from the United States of America.

In order to investigate the roles of quality requirements for antibiotic products in Japan, from historical and hygienic aspects, we examined and analyzed how technology and knowledge in the production and quality control of penicillin were introduced from the United States of America, applied, and further developed. Owing to the strong support of Colonel Crawford Sams, the chief of the Public Health and Welfare Section of the Supreme Commander for Allied Power/General Headquarters, via the Ministry of Welfare in Japan, the technology and knowledge were acquired from an experienced leader, Dr. Jackson W. Foster, and as a result, domestic production of penicillin was successfully achieved in amounts required to meet national demands sufficiently within three years in a devastated post-war-torn Japan. Based on the consensus that penicillin should be dealt with as "biological products" similar to vaccines and antisera, the quality standards for penicillin were enacted as the "Minimum Requirements for Penicillin (MRP)" on the 1st of May 1947. Due to the development of penicillin production technology, the quality standards of penicillin provided by the MRP were revised often to higher levels ; content of the active element from no less than 60 units/mg (purity 3.8%) to no less than 1,430 units/mg (purity 89.7%). Regarding the penicillin preparations, the content of the active ingredient per vial was changed from 30,000 units at the beginning, to 100,000 units in January 1948, to 3,000,000 units in December 1950, and two preparations containing 200,000 units and 1,000,000 units per vial are currently available, according to clinical convenience.

[Historical and Hygienic Aspects on Roles of Quality Requirements for Antibiotic Products in Japan: Part 2--Achievements of Domestic Production of Penicillin and Streptomycin].

Domestic production of penicillin was initiated in 1946 and that of streptomycin in 1950. In the early days, however, the quality of products was considerably lower and the capacity of production small. Surprisingly, there was a sufficient amount of penicillin preparations, with a purity of 85% or more, satisfying domestic demand within three years (1949). In the case of streptomycin, within three years (1953), preparations with a purity two-fold higher than initially available were produced in amounts sufficient to meet both domestic demand and create a surplus availability for exporting purposes. Such increases in quality and production were considered to be made possible by strict quality control of penicillin and streptomycin preparations, based on "Minimum Requirements for Penicillin" established in May 1947 and "Minimum Requirements for Streptomycin" established in December 1949. These requirements were also amended over time in order to provide even higher quality standards in response to the evolving improvements in production processes. Life-threatening diseases such as septicemia and pneumonia were controlled by the sufficient supply of high-quality penicillin preparations and the mortality rate of tuberculosis, regarded as a national disease at the time, markedly decreased by that of streptomycin preparations. Achievements of domestic production of penicillin and streptomycin were considered important factors that contributed greatly to the maintenance of public health in Japan.

Impact of penicillin nonsusceptibility on clinical outcomes of patients with nonmeningeal Streptococcus pneumoniae bacteremia in the era of the 2008 clinical and laboratory standards institute penicillin breakpoints.

To investigate the impact of penicillin nonsusceptibility on clinical outcomes of patients with nonmeningeal Streptococcus pneumoniae bacteremia (SPB), a retrospective cohort study was performed. The characteristics of 39 patients with penicillin-nonsusceptible SPB (PNSPB) were compared to those of a group of age- and sex-matched patients (n = 78) with penicillin-susceptible SPB (PSSPB). Susceptibility to penicillin was redetermined by using the revised Clinical and Laboratory Standards Institute (CLSI) penicillin breakpoints in CLSI document M100-S18. Although the PNSPB group tended to have more serious initial manifestations than the PSSPB group, the two groups did not differ significantly in terms of their 30-day mortality rates (30.8% versus 23.1%; P = 0.37) or the duration of hospital stay (median number of days, 14 versus 12; P = 0.89). Broad-spectrum antimicrobial agents, such as extended-spectrum cephalosporins, vancomycin, and carbapenem, were frequently used in both the PNSPB and PSSPB groups. Multivariate analysis revealed that ceftriaxone nonsusceptibility (adjusted odds ratio [aOR] = 4.88; 95% confidence interval [CI] = 1.07 to 22.27; P = 0.041) was one of the independent risk factors for 30-day mortality. Thus, when the 2008 CLSI penicillin breakpoints are applied and the current clinical practice of using wide-spectrum empirical antimicrobial agents is pursued, fatal outcomes in patients with nonmeningeal SPB that can be attributed to penicillin nonsusceptibility are likely to be rare. Further studies that examine the clinical impact of ceftriaxone nonsusceptibility in nonmningeal SPB may be warranted.

Quality and bioavailability of ampicillin capsules dispensed in a Nigerian semi-urban community.

Five samples of ampicillin capsules with a label claim of 250 mg were purchased from different dispensing points in a small town in Nigeria. The pharmaceutical quality of the products and a sample from a batch produced by a local manufacturer was evaluated and five of the capsule samples were employed in an in vivo bioavailability study. Three of the five capsule samples from dispensing points were found to be of lower quality than the officially prescribed standards of pharmaceutical quality. The quality lapses observed were sufficient to bring about determinable differences in biological availability. The results demonstrate that ampicillin capsules of sub-standard chemical quality are being dispensed within the study sources from authorised and unauthorised sources and that this may have biological, clinical and epidemiological consequences.

Associations between off-label feed additives and farm size, veterinary consultant use, and animal age.

Data from the United States National Swine Survey collected by the National Animal Health Monitoring System were used to describe the use of feed additives in swine feeds. Data were collected from 710 farms. The concentration of feed additives expressed in grams per ton of complete feed was described by stage of production, and the use of feed additives above the labeled treatment levels (i.e. off-label) was identified. Of the 3328 feeds, about 79% contained feed additives used in the labeled manner. For all classes of pigs, the prevalence of labeled feed additive use was greater than 75%. Penicillin was used according to its label most often, followed by apramycin, bacitracin, tetracyclines, lincomycin, and tylosin. Carbadox had the highest prevalence of off-label use. Of the 699 feeds that included feed additives in an off-label manner, about 57% included additives at greater than the recommended concentrations or were fed to an incorrect class of pig. About 56% of the feeds had off-label combinations of additives. Small farms were more likely to use rations with no feed additives than intermediate or large farms (P < 0.001). Of those farms using feed additives, the odds of a small farm using all feed additives in the labeled manner was 7.7 times that of an intermediate or large farm (P < 0.0001). After controlling for herd size, producers who used a veterinary consultant were 2.1 times more likely to use feeds with feed additives (P < 0.0001).

Susceptibility testing of anaerobic bacteria. Regression lines for six antibiotics determined with and without prediffusion.

The relationship between susceptibility testing by an agar dilution test and a tablet diffusion test was studied for 60 anaerobic bacteria (20 B. fragilis, 20 anaerobic cocci, 20 Clostridium species). For cefoxitin, no prediffusion and prediffusion times of one h, three h, 12 h, 24 h and 48 h were examined. For metronidazole, erythromycin, clindamycin, penicillin and imipenem, only 24 h prediffusion and no prediffusion were studied. Measurements were made after incubation for 24 h and 48 h. Prediffusion improved the correlation for all antibiotics tested, and 24 h prediffusion gave the best results. The slope of the regression line increased and the influence of the individual growth parameters on zone size was reduced. Prediction of susceptibility based on three zone breakpoints to estimate MIC was also better with 24 h prediffusion. However, the variation about the regression line for many of the antibiotics was still extremely high. Measurements after 24 h and 48 h incubation times showed almost identical regression equations, except for erythromycin, where the regression lines differed.

Antigenic high molecular weight material in penicillin preparations.

Using a radioimmunoassay, RIA, small amounts of high molecular weight antigens have been reproducibly identified in both biosynthetic and semisynthetic brands of penicillin. These impurities were found to be eliminated by simple chemical means. Measures to avoid this type of contaminants in penicillin preparations should be undertaken because of the immunogenic nature of the contaminants resulting in increased risk of sensitization of patients to penicillin.

Experimental evidence of a decreased incidence of penicillin allergy through use of pure penicillins.

The results revealed the presence of high molecular weight impurities in commercially available penicillins, measured with a radioimmuno assay. The impurities had penicilloyl specificity and induced antibody formation in mice when the contaminated penicillin was administered in 50 mg/kg body weight daily for ten day periods with a 20 to 30 day interval. Penicillin of high purity similarly administered produced very few antibodies. Furthermore, experimentally contaminated penicillin given according to the same schedule caused IgE antibody formation against the penicilloyl moiety, while pure penicillin did not. These findings were explained by the weak immunogenicity of isologous penicilloylated serum albumin in rabbits both regarding the IgE and the IgG/IgM antibody formation compared to the immunogenicity of heterologous bovine serum albumin similarly penicilloylated.