ResearchPad - penicillin https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Successful improvement of antibiotic prescribing at Primary Care in Andalusia following the implementation of an antimicrobial guide through multifaceted interventions: An interrupted time-series analysis]]> https://www.researchpad.co/article/elastic_article_14725 Most effective strategies designed to improve antimicrobial prescribing have multiple approaches. We assessed the impact of the implementation of a rigorous antimicrobial guide and subsequent multifaceted interventions aimed at improving antimicrobial use in Primary Care.MethodsA quasi-experimental study was designed. Interventions aimed at achieving a good implementation of the guide consisted of the development of electronic decision support tools, local training meetings, regional workshops, conferences, targets for rates of antibiotic prescribing linked to financial incentives, feedback on antibiotic prescribing, and the implementation of a structured educational antimicrobial stewardship program. Interventions started in 2011, and continued until 2018. Outcomes: rates of antibiotics use, calculated into defined daily doses per 1,000 inhabitants-day (DID). An interrupted time-series analysis was conducted. The study ran from January 2004 until December 2018.ResultsOverall annual antibiotic prescribing rates showed increasing trends in the pre-intervention period. Interventions were followed by significant changes on trends with a decline over time in antibiotic prescribing. Overall antibiotic rates dropped by 28% in the Aljarafe Area and 22% in Andalusia between 2011 and 2018, at rates of -0.90 DID per year (95%CI:-1.05 to -0.75) in Aljarafe, and -0.78 DID (95%CI:-0.95 to -0.60) in Andalusia. Reductions occurred at the expense of the strong decline of penicillins use (33% in Aljarafe, 25% in Andalusia), and more precisely, amoxicillin clavulanate, whose prescription plummeted by around 50%. Quinolones rates decreased before interventions, and continued to decline following interventions with more pronounced downward trends. Decreasing cephalosporins trends continued to decline, at a lesser extent, following interventions in Andalusia. Trends of macrolides rates went from a downward trend to an upward trend from 2011 to 2018.ConclusionsMultifaceted interventions following the delivering of a rigorous antimicrobial guide, maintained in long-term, with strong institutional support, could led to sustained reductions in antibiotic prescribing in Primary Care. ]]> <![CDATA[Antibiotic use for Australian Aboriginal children in three remote Northern Territory communities]]> https://www.researchpad.co/article/N999fa4e6-a15c-456a-862e-2e1ce88316a9

Objective

To describe antibiotic prescription rates for Australian Aboriginal children aged <2 years living in three remote Northern Territory communities.

Design

A retrospective cohort study using electronic health records.

Setting

Three primary health care centres located in the Katherine East region.

Participants

Consent was obtained from 149 mothers to extract data from 196 child records. There were 124 children born between January 2010 and July 2014 who resided in one of the three chosen communities and had electronic health records for their first two years of life.

Main outcome measures

Antibiotic prescription rates, factors associated with antibiotic prescription and factors associated with appropriate antibiotic prescription.

Results

There were 5,675 Primary Health Care (PHC) encounters for 124 children (median 41, IQR 25.5, 64). Of the 5,675 PHC encounters, 1,542 (27%) recorded at least one infection (total 1,777) and 1,330 (23%) had at least one antibiotic prescription recorded (total 1,468). Children had a median five (IQR 2, 9) prescriptions in both their first and second year of life, with a prescription rate of 5.99/person year (95% CI 5.35, 6.63). Acute otitis media was the most common infection (683 records, 38%) and Amoxycillin was the most commonly prescribed antibiotic (797 prescriptions, 54%). Of the 1,468 recorded prescriptions, 398 (27%) had no infection recorded and 116 (8%) with an infection recorded were not aligned with local treatment guidelines.

Conclusion

Prescription rates for Australian Aboriginal children in these communities are significantly higher than that reported nationally for non-Aboriginal Australians. Prescriptions predominantly aligned with treatment guidelines in this setting where there is a high burden of infectious disease.

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<![CDATA[A novel cell-free method to culture Schistosoma mansoni from cercariae to juvenile worm stages for in vitro drug testing]]> https://www.researchpad.co/article/5c58d63ed5eed0c484031973

Background

The arsenal in anthelminthic treatment against schistosomiasis is limited and relies almost exclusively on a single drug, praziquantel (PZQ). Thus, resistance to PZQ could constitute a major threat. Even though PZQ is potent in killing adult worms, its activity against earlier stages is limited. Current in vitro drug screening strategies depend on newly transformed schistosomula (NTS) for initial hit identification, thereby limiting sensitivity to new compounds predominantly active in later developmental stages. Therefore, the aim of this study was to establish a highly standardized, straightforward and reliable culture method to generate and maintain advanced larval stages in vitro. We present here how this method can be a valuable tool to test drug efficacy at each intermediate larval stage, reducing the reliance on animal use (3Rs).

Methodology/Principal findings

Cercariae were mechanically transformed into skin-stage (SkS) schistosomula and successfully cultured for up to four weeks with no loss in viability in a commercially available medium. Under these serum- and cell-free conditions, development halted at the lung-stage (LuS). However, the addition of human serum (HSe) propelled further development into liver stage (LiS) worms within eight weeks. Skin and lung stages, as well as LiS, were submitted to 96-well drug screening assays using known anti-schistosomal compounds such as PZQ, oxamniquine (OXM), mefloquine (MFQ) and artemether (ART). Our findings showed stage-dependent differences in larval susceptibility to these compounds.

Conclusion

With this robust and highly standardized in vitro assay, important developmental stages of S. mansoni up to LiS worms can be generated and maintained over prolonged periods of time. The phenotype of LiS worms, when exposed to reference drugs, was comparable to most previously published works for ex vivo harvested adult worms. Therefore, this in vitro assay can help reduce reliance on animal experiments in search for new anti-schistosomal drugs.

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<![CDATA[Associations between use of macrolide antibiotics during pregnancy and adverse child outcomes: A systematic review and meta-analysis]]> https://www.researchpad.co/article/5c75abfad5eed0c484d07f62

Background

Evidence on adverse effects of maternal macrolide use during pregnancy is inconsistent. We conducted a systematic review and meta-analysis to investigate the association between macrolide use during pregnancy and adverse fetal and child outcomes.

Methods and findings

We included observational studies and randomised controlled trials (RCTs) that recorded macrolide use during pregnancy and child outcomes. We prioritized comparisons of macrolides with alternative antibiotics (mainly penicillins or cephalosporins) for comparability of indication and effect. Random effects meta-analysis was used to derive pooled odds ratios (OR) for each outcome. Subgroup analyses were performed according to specific types (generic forms) of macrolide.

Of 11,186 citations identified, 19 (10 observational, 9 RCTs) studies were included (21 articles including 228,556 participants). Macrolide prescribing during pregnancy was associated with an increased risk of miscarriage (pooled ORobs 1·82, 95% CI 1·57–2·11, three studies, I2 = 0%), cerebral palsy and/or epilepsy (ORobs 1·78, 1·18–2·69; one study), epilepsy alone (ORobs 2·02, 1·30–3·14, one study; ORRCT 1.03, 0.79–1.35, two studies), and gastrointestinal malformations (ORobs 1·56, 1·05–2·32, two studies) compared with alternative antibiotics. We found no evidence of an adverse effect on 12 other malformations, stillbirth, or neonatal death. Results were robust to excluding studies with high risk of bias.

Conclusions

Consistent evidence of an increased risk of miscarriage in observational studies and uncertain risks of cerebral palsy and epilepsy warrant cautious use of macrolide in pregnancy with warnings in drug safety leaflets and use of alternative antibiotics where appropriate. As macrolides are the third most commonly used class of antibiotics, it is important to confirm these results with high quality studies.

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<![CDATA[A cross-sectional study on the prevalence of antibiotic use prior to laboratory tests at two Ghanaian hospitals]]> https://www.researchpad.co/article/5c478c46d5eed0c484bd141b

There has been a significant rise in global antibiotic use in recent years. Development of resistance has been linked to easy accessibility, lack of regulation of sale, increased tendency to self-medicate and the lack of public knowledge. The increase in antibiotic misuse, including self-medication, has not been well documented in developing countries. Antibiotic use prior to visiting health facilities has been found to be prevalent in developing countries. It has been identified by some studies to increase the likelihood of missed diagnoses and influence the outcome of bacteriological tests. This study is aimed at determining the prevalence of prior antibiotic use through a cross-sectional survey of patients undergoing laboratory tests at two health facilities in Ghana. Face-to-face questionnaires were used to interview 261 individuals chosen by random sampling of patients visiting the bacteriology laboratory of the hospitals within a two-month period. The questionnaire investigated participant demographic characteristics, knowledge about antibiotics and the nature of antibiotic use. Antibiotic property detection bioassay was performed on patient’s urine sample using a disk diffusion method to accurately determine antibiotic use within 72 hours. Culture results were used as an index to evaluate the effect of prior antibiotic use on bacteriological tests. Out of a 261 participants enrolled, 19.9% (95% CI, 14.9–24.9) acknowledged using antibiotics prior to their visit to the laboratory during the study period. On the contrary, 31.4% (95% CI, 25.7–37.5) of participants’ urine samples were positive for antimicrobial activity. Participants within the age ranges of 20–30, 31–40 and 41–50 years had significantly lower odds of urine antimicrobial activity. Participants who had urine antimicrobial activity were more likely to have no growth on their culture plates than participants who had no urine antimicrobial activity [OR 2.39(1.37–4.18), p = 0.002]. The most commonly used antibiotics were the penicillins, fluoroquinolones and metronidazole. Although, majority of the participant (54.8%) had knowledge of antibiotics, most of them had inadequate information on their proper use. The commonest indications for antibiotic use were aches and pains (30.3%), diarrhoea (43.3%) and urinary tract infections (28.0%). Prior antibiotic use was found to increase the likelihood of obtaining a culture negative result and can affect the outcome of bacteriological tests.

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<![CDATA[Topical treatment with gallium maltolate reduces Treponema pallidum subsp. pertenue burden in primary experimental lesions in a rabbit model of yaws]]> https://www.researchpad.co/article/5c366801d5eed0c4841a6d64

Background

Gallium is a semi-metallic element known since the 1930s to have antimicrobial activity. This activity stems primarily from gallium's ability to mimic trivalent iron and disrupt specific Fe(III)-dependent pathways, particularly DNA synthesis (due to inhibition of ribonucleotide reductase). Because of its novel mechanism of action, gallium is currently being investigated as a new antibacterial agent, particularly in light of the increasing resistance of many pathogenic bacteria to existing antibiotics. Gallium maltolate (GaM) is being developed as an orally and topically administrable form of gallium. Yaws is a neglected tropical disease affecting mainly the skin and skeletal system of children in underprivileged settings. It is currently the object of a WHO-promoted eradication campaign using mass administration of the macrolide azithromycin, an antibiotic to which the yaws agent Treponema pallidum subsp. pertenue has slowly begun to develop genetic resistance.

Methods

Because yaws transmission is mainly due to direct skin contact with an infectious skin lesion, we evaluated the treponemicidal activity of GaM applied topically to skin lesions in a rabbit model of yaws. Treatment efficacy was evaluated by measuring lesion diameter, treponemal burden in lesion aspirates as determined by dark field microscopy and amplification of treponemal RNA, serology, and immunohistochemistry of biopsied tissue samples.

Results

Our results show that topical GaM was effective in reducing treponemal burden in yaws experimental lesions, particularly when applied at the first sign of lesion appearance but, as expected, did not prevent pathogen dissemination.

Conclusion

Early administration of GaM to yaws lesions could reduce the infectivity of the lesions and thus yaws transmission, potentially contributing to current and future yaws control campaigns.

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<![CDATA[Penicillin skin testing in methicillin-sensitive staphylococcus aureus bacteremia: A cost-effectiveness analysis]]> https://www.researchpad.co/article/5c3d0135d5eed0c48403937e

Background

Beta-lactams are the mainstay for treating methicillin-susceptible Staphylococcus aureus (MSSA) infections complicated by bacteremia due to superior outcomes compared with vancomycin. With approximately 11% of inpatients reporting a penicillin (PCN) allergy, many patients receive suboptimal treatment for MSSA bacteremia.

Objective

Evaluate the cost-effectiveness of penicillin skin testing (PST) in adult patients with self-reported PCN allergy in an inpatient setting undergoing treatment for MSSA bacteremia.

Methods

A decision analytic model was developed comparing an acute care PST intervention to a scenario with no confirmatory allergy testing. The primary outcome was the incremental cost-effectiveness ratio (ICER) from the health-sector perspective over a 1-year time horizon using quality-adjusted life years (QALYs) as the measure for effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty of the ICER estimation.

Results

Over a 1-year time horizon, PST services applied to all MSSA bacteremia patients reporting a PCN-allergy would result in a cost per patient of $12,559 and 0.73 QALYs while no PST services would have a higher cost per patient of $13,219 and 0.66 QALYs per patient. This resulted in a cost-effectiveness estimate of -$9,429 per QALY gained. Varying the cost of implementing PST services determined a break-even point of $959.98 where any PST cost less than this amount would actually be cost saving.

Conclusions

Patients reporting a PCN allergy on admission may receive sub-optimal alternative therapies to beta-lactams, such as vancomycin, for MSSA bacteremia. This economic analysis demonstrates that inpatient PST services confirming PCN allergy are cost-effective for patients with MSSA bacteremia.

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<![CDATA[Ixodes pacificus Ticks Maintain Embryogenesis and Egg Hatching after Antibiotic Treatment of Rickettsia Endosymbiont]]> https://www.researchpad.co/article/5989db02ab0ee8fa60bc7023

Rickettsia is a genus of intracellular bacteria that causes a variety of diseases in humans and other mammals and associates with a diverse group of arthropods. Although Rickettsia appears to be common in ticks, most Rickettsia-tick relationships remain generally uncharacterized. The most intimate of these associations is Rickettsia species phylotype G021, a maternally and transstadially transmitted endosymbiont that resides in 100% of I. pacificus in California. We investigated the effects of this Rickettsia phylotype on I. pacificus reproductive fitness using selective antibiotic treatment. Ciprofloxacin was 10-fold more effective than tetracycline in eliminating Rickettsia from I. pacificus, and quantitative PCR results showed that eggs from the ciprofloxacin-treated ticks contained an average of 0.02 Rickettsia per egg cell as opposed to the average of 0.2 in the tetracycline-treated ticks. Ampicillin did not significantly affect the number of Rickettsia per tick cell in adults or eggs compared to the water-injected control ticks. We found no relationship between tick embryogenesis and rickettsial density in engorged I. pacificus females. Tetracycline treatment significantly delayed oviposition of I. pacificus ticks, but the antibiotic’s effect was unlikely related to Rickettsia. We also demonstrated that Rickettsia-free eggs could successfully develop into larvae without any significant decrease in hatching compared to eggs containing Rickettsia. No significant differences in the incubation period, egg hatching rate, and the number of larvae were found between any of the antibiotic-treated groups and the water-injected tick control. We concluded that Rickettsia species phylotype G021 does not have an apparent effect on embryogenesis, oviposition, and egg hatching of I. pacificus.

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<![CDATA[Colonization prevalence and antibiotic susceptibility of Group B Streptococcus in pregnant women over a 6-year period in Dongguan, China]]> https://www.researchpad.co/article/5aafc6bf463d7e7d7e2e875f

This study investigated the prevalence of recto-vaginal Group B Streptococcus (GBS) colonization, serotype distribution, and antimicrobial susceptibility patterns among pregnant women in Dongguan, China. Recto-vaginal swabs were collected from pregnant women at gestational age 35–37 weeks between January 1st 2009 and December 31st 2014. Isolates were serotyped by latex-agglutination and were tested against seven antimicrobials by disk diffusion. Of 7,726 pregnant women who completed GBS testing, 636 (8.2%) were GBS carriers. Of 153 GBS isolates available for typing, 6 serotypes (Ia, Ib, III, V, VI and VIII) were identified with type III being predominant, while 9 (5.9%) were non-typable isolates. All isolates were sensitive to penicillin, ceftriaxone, linezolid and vancomycin, whereas 52.4% were resistant to clindamycin, 25.9% were resistant to levofloxacin and 64.9% were resistant to erythromycin. This study showed the recto-vaginal colonization prevalence of GBS in Dongguan is significant. Due to 100% susceptibility to penicillin of all GBS samples, penicillin remains the first recommendation for treatment and prevention against GBS infection. Susceptibility testing should be performed for women allergic to penicillin in order to choose the most appropriate antibacterial agents for treatment and prevention of vertical transmission to neonates. In addition, we suggest establishing standard processes for GBS culture and identification in China as early as possible.

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<![CDATA[Antibacterial Compounds of Canadian Honeys Target Bacterial Cell Wall Inducing Phenotype Changes, Growth Inhibition and Cell Lysis That Resemble Action of β-Lactam Antibiotics]]> https://www.researchpad.co/article/5989db4eab0ee8fa60bdb4f8

Honeys show a desirable broad spectrum activity against Gram-positive and negative bacteria making antibacterial activity an intrinsic property of honey and a desirable source for new drug development. The cellular targets and underlying mechanism of action of honey antibacterial compounds remain largely unknown. To facilitate the target discovery, we employed a method of phenotypic profiling by directly comparing morphological changes in Escherichia coli induced by honeys to that of ampicillin, the cell wall-active β-lactam of known mechanism of action. Firstly, we demonstrated the purity of tested honeys from potential β-lactam contaminations using quantitative LC-ESI-MS. Exposure of log-phase E. coli to honey or ampicillin resulted in time- and concentration-dependent changes in bacterial cell shape with the appearance of filamentous phenotypes at sub-inhibitory concentrations and spheroplasts at the MBC. Cell wall destruction by both agents, clearly visible on microscopic micrographs, was accompanied by increased permeability of the lipopolysaccharide outer membrane as indicated by fluorescence-activated cell sorting (FACS). More than 90% E. coli exposed to honey or ampicillin became permeable to propidium iodide. Consistently with the FACS results, both honey-treated and ampicillin-treated E. coli cells released lipopolysaccharide endotoxins at comparable levels, which were significantly higher than controls (p<0.0001). E. coli cells transformed with the ampicillin-resistance gene (β–lactamase) remained sensitive to honey, displayed the same level of cytotoxicity, cell shape changes and endotoxin release as ampicillin-sensitive cells. As expected, β–lactamase protected the host cell from antibacterial action of ampicillin. Thus, both honey and ampicillin induced similar structural changes to the cell wall and LPS and that this ability underlies antibacterial activities of both agents. Since the cell wall is critical for cell growth and survival, honey active compounds would be highly applicable for therapeutic purposes while differences in the mode of action between honey and ampicillin may provide clinical advantage in eradicating β-lactam-resistant pathogens.

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<![CDATA[Broad-Spectrum Antibiotic Treatment and Subsequent Childhood Type 1 Diabetes: A Nationwide Danish Cohort Study]]> https://www.researchpad.co/article/5989da05ab0ee8fa60b75ab7

Background

Studies link antibiotic treatment and delivery by cesarean section with increased risk of chronic diseases through changes of the gut-microbiota. We aimed to evaluate the association of broad-spectrum antibiotic treatment during the first two years of life with subsequent onset of childhood type 1 diabetes and the potential effect-modification by mode of delivery.

Materials and Methods

A Danish nationwide cohort study including all singletons born during 1997–2010. End of follow-up by December 2012. Four national registers provided information on antibiotic redemptions, outcome and confounders. Redemptions of antibiotic prescriptions during the first two years of life was classified into narrow-spectrum or broad-spectrum antibiotics. Children were followed from age two to fourteen, both inclusive. The risk of type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 858,201 singletons contributed 5,906,069 person-years, during which 1,503 children developed type 1 diabetes.

Results

Redemption of broad-spectrum antibiotics during the first two years of life was associated with an increased rate of type 1 diabetes during the following 13 years of life (HR 1.13; 95% CI 1.02 to 1.25), however, the rate was modified by mode of delivery. Broad-spectrum antibiotics were associated with an increased rate of type 1 diabetes in children delivered by either intrapartum cesarean section (HR 1.70; 95% CI 1.15 to 2.51) or prelabor cesarean section (HR 1.63; 95% CI 1.11 to 2.39), but not in vaginally delivered children. Number needed to harm was 433 and 562, respectively. The association with broad-spectrum antibiotics was not modified by parity, genetic predisposition or maternal redemption of antibiotics during pregnancy or lactation.

Conclusions

Redemption of broad-spectrum antibiotics during infancy is associated with an increased risk of childhood type 1 diabetes in children delivered by cesarean section.

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<![CDATA[Subfamily-Specific Adaptations in the Structures of Two Penicillin-Binding Proteins from Mycobacterium tuberculosis]]> https://www.researchpad.co/article/5989dab5ab0ee8fa60bac79b

Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows that Rv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis.

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<![CDATA[Lactobacillus rhamnosus GG Intake Modifies Preschool Children’s Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use]]> https://www.researchpad.co/article/5989dac1ab0ee8fa60bb0b1d

Antibiotic use is considered among the most severe causes of disturbance to children’s developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children’s microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children’s antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2–7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use.

Trial Registration: ClinicalTrials.gov NCT01014676

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<![CDATA[Documenting Penicillin Allergy: The Impact of Inconsistency]]> https://www.researchpad.co/article/5989d9f8ab0ee8fa60b71127

Background

Allergy documentation is frequently inconsistent and incomplete. The impact of this variability on subsequent treatment is not well described.

Objective

To determine how allergy documentation affects subsequent antibiotic choice.

Design

Retrospective, cohort study.

Participants

232,616 adult patients seen by 199 primary care providers (PCPs) between January 1, 2009 and January 1, 2014 at an academic medical system.

Main Measures

Inter-physician variation in beta-lactam allergy documentation; antibiotic treatment following beta-lactam allergy documentation.

Key Results

15.6% of patients had a reported beta-lactam allergy. Of those patients, 39.8% had a specific allergen identified and 22.7% had allergic reaction characteristics documented. Variation between PCPs was greater than would be expected by chance (all p<0.001) in the percentage of their patients with a documented beta-lactam allergy (7.9% to 24.8%), identification of a specific allergen (e.g. amoxicillin as opposed to “penicillins”) (24.0% to 58.2%) and documentation of the reaction characteristics (5.4% to 51.9%). After beta-lactam allergy documentation, patients were less likely to receive penicillins (Relative Risk [RR] 0.16 [95% Confidence Interval: 0.15–0.17]) and cephalosporins (RR 0.28 [95% CI 0.27–0.30]) and more likely to receive fluoroquinolones (RR 1.5 [95% CI 1.5–1.6]), clindamycin (RR 3.8 [95% CI 3.6–4.0]) and vancomycin (RR 5.0 [95% CI 4.3–5.8]). Among patients with beta-lactam allergy, rechallenge was more likely when a specific allergen was identified (RR 1.6 [95% CI 1.5–1.8]) and when reaction characteristics were documented (RR 2.0 [95% CI 1.8–2.2]).

Conclusions

Provider documentation of beta-lactam allergy is highly variable, and details of the allergy are infrequently documented. Classification of a patient as beta-lactam allergic and incomplete documentation regarding the details of the allergy lead to beta-lactam avoidance and use of other antimicrobial agents, behaviors that may adversely impact care quality and cost.

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<![CDATA[Comparison of Serotype Prevalence of Pneumococci Isolated from Middle Ear, Lower Respiratory Tract and Invasive Disease Prior to Vaccination in Iceland]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdba26

Background

Information on pneumococcal serotype distribution before vaccination is a prerequisite for evaluation of vaccine effect. The aim was to investigate the prevalence of pneumococcal serotypes isolated from middle ear (ME), lower respiratory tract (LRT) and from invasive disease (IPD) in Iceland prior to implementation of ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV-10) into the infant vaccination program (April 2011).

Methods and findings

All isolates cultured 2007–2011 from ME, LRT and IPD identified as pneumococci were serotyped and tested for susceptibility at the Clinical Microbiology Department, Landspitali University Hospital that serves approximately 85% of the Icelandic population. Pneumococcal isolates were 1711 and 1616 (94.4%) were available for serotyping and included. Isolates belonging to PHiD-CV10 serotypes (VTs) were 1052 (65.1%). Isolates from ME were 879 (54.4%), with 639 (72.7%) from 0–1 year old patients and 651 of VTs (74%). Isolates from LRT were 564 (34.9%), with 292 (51.8%) from ≥65 years old patients, and 300 (53.2%) of VTs. IPD isolates were 173 (10.7%), although more evenly distributed according to age than isolates from the other sites most were from adults and the youngest age group,101 (58.4%) isolates were of VTs. The most common serotype was 19F, 583 (36.1%). Its prevalence was highest in ME, 400 (45.5%), 172 (30.5%) in LRT and 11 isolates (6.4%), in IPD. Penicillin non-susceptible isolates were 651 (40.3%), mainly belonging to VTs, 611 (93.9%), including 535 (82.2%) of 19F.

Conclusions

Multiresistant isolates of serotype 19F were highly prevalent, especially from ME of young children but also from LRT of adults. Serotype 14 was the most common serotype in IPD. The rate of VTs was high and almost all PNSP were of VTs. There was great difference in vaccine coverage between sampling sites, also reflecting difference in vaccine coverage by age groups.

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<![CDATA[In Vitro Selective Growth-Inhibitory Effect of 8-Hydroxyquinoline on Clostridium perfringens versus Bifidobacteria in a Medium Containing Chicken Ileal Digesta]]> https://www.researchpad.co/article/5989db47ab0ee8fa60bd8c65

Clostridium perfringens-induced necrotic enteritis is generally controlled by antibiotics. However, because of increasing antibiotic resistance, other antibacterial agents are required, preferably ones that do not affect the beneficial intestinal microbiota of the host. This study evaluated the in vitro selective growth-inhibitory effect of 8-hydroxyquinoline (8HQ) on C. perfringens vs. bifidobacteria in a medium containing chicken ileal digesta. Prior to the experiments, the minimum inhibitory concentrations of 8HQ and penicillin G were determined by broth microdilution assay. The minimum inhibitory concentration values of 8HQ for C. perfringens were 16–32 times lower than the values for bifidobacteria. Treatment of autoclaved and non-autoclaved chicken ileal digesta with 8HQ showed a selective anticlostridial effect. After incubation of C. perfringens with autoclaved ileal digesta for 3 h, all 8HQ concentrations tested (32–2048 μg/mL) significantly reduced C. perfringens bacterial count. In contrast, the same treatment had no or only a slight effect on bifidobacteria counts. Unlike 8HQ, penicillin G did not exhibit any selectivity. Similar results were obtained after incubation for 24 h. In non-autoclaved ileal digesta, all 8HQ concentrations tested significantly reduced C. perfringens bacterial counts after incubation for 30 min and 3 h, while no effect was observed on bifidobacteria. These results suggest that 8HQ may serve as a prospective veterinary compound for use against necrotic enteritis in poultry.

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<![CDATA[Nasopharyngeal Pneumococcal Carriage among Healthy Children in Cyprus Post Widespread Simultaneous Implementation of PCV10 and PCV13 Vaccines]]> https://www.researchpad.co/article/5989db40ab0ee8fa60bd674f

The objective of the study was to describe the incidence of pneumococcal nasopharyngeal carriage, serotype distribution and antibiotic resistance profile of pneumococcal nasopharyngeal isolates in healthy children aged 6 to 36 months following the implementation of conjugate vaccines. A nasopharyngeal swab was collected from 1105 healthy children following a stratified random sampling between September 2013 and April 2014. Demographics, vaccination status and data on possible risk factors were recorded. Isolates were serotyped and tested for antibiotic susceptibility. The nasopharyngeal carriage rate was 25.3%. Among 1105 children enrolled, 393 had received PCV13 and 685 PCV10. The prevailing isolated serotypes were: 23A (14.3%), 15A (8.9%), 6C (8.6%), 23B (7.5%), 19A (5.4%) and 15B (5%). The proportion of non-vaccine serotypes, PCV10 serotypes, PCV13 additional serotypes (3, 6A, 19A) was 76.8%, 2.1% and 10.4% respectively. Although children, who were fully or partially vaccinated with PCV13, were 63% less likely to be colonized with additional PCV13 serotypes compared to those vaccinated with PCV10, the difference is not significant (95%Cl = 0.14–1.02, p = 0.053). The highest antibiotic non-susceptible rates were found for erythromycin (28.2%) and penicillin (27.9%). The overall multidrug resistance rate was 13.2%, with serotypes 24F (4/6), 15A (14/25) and 19A (6/15) being the main contributors. Carriage rate was similar between children vaccinated with PCV10 or PCV13. The high incidence of 15A serotype which is also multidrug resistant should be underlined. Ongoing surveillance is needed to monitor the dynamics on nasopharyngeal carriage.

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<![CDATA[Comparable Effectiveness of First Week Treatment with Anti-Staphylococcal Penicillin versus Cephalosporin in Methicillin-Sensitive Staphylococcus aureus Bacteremia: A Propensity-Score Adjusted Retrospective Study]]> https://www.researchpad.co/article/5989db4eab0ee8fa60bdb269

The objective was to compare the prognostic impact of first week treatment with anti-staphylococcal penicillin (ASP) versus cephalosporin in methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB). Altogether 580 patients were retrospectively followed and categorized according to first week treatment; 84% (488) received ASP (cloxacillin) and 16% (92) cephalosporin (cefuroxime or ceftriaxone). SAB management was optimized with formal bedside infectious disease specialist consultation in 88%, deep infection foci diagnosed in 77% and adjunctive rifampicin therapy given to 61% of patients. The total case fatality in 580 patients was 12% at 28 days and 18% at 90 days. When comparing effectiveness of first week ASP versus cephalosporin treatment there were no significant differences in 28-days (11% vs. 12%, OR; 1.05, 95% CI, 0.53–2.09) or 90-days (17% vs. 21% OR; 1.25, 95% CI, 0.72–2.19) outcome. In univariate analysis no prognostic impact of either first week ASP or cephalosporin treatment was observed for 28-days (OR; 0.96, 95% CI, 0.48–1.90 and OR; 1.05, 95% CI, 0.53–2.09) or 90-days (OR; 0.80, 95% CI, 0.46–1.39 and OR; 1.25, 95% CI, 0.72–2.19) outcome. Propensity-score adjusted Cox proportional regression analysis for first week treatment with cephalosporin demonstrated no significant prognostic impact at 28-days (HR 1.54, 95% CI 0.72–3.23) or 90-days (HR 1.56, 95% CI 0.88–2.86). In conclusion: There is a comparable effectiveness with respect to 28- and 90-days outcome for first week treatment with ASP versus cephalosporin in MS-SAB. The results indicate that the difference in prognostic impact between first week ASP and cephalosporin may be non-significant in patient cohorts with SAB management optimized by infectious disease specialist consultation.

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<![CDATA[Risk Factors of Early Otitis Media in the Danish National Birth Cohort]]> https://www.researchpad.co/article/5989da59ab0ee8fa60b8f73d

Objective

To assess risk factors of otitis media (OM) in six-months-old children.

Method

The sample consisted of 69,105 mothers and their children from the Danish National Birth Cohort. The women were interviewed twice during pregnancy and again 6 months after birth. The outcome “one or more” maternal reported episodes of OM at age six months. In total 37 factors were assessed, covering prenatal, maternal, perinatal and postnatal factors.

Results

At age six months 5.3% (95% CI 5.1–5.5) of the children had experienced one or more episodes of OM. From the regression analysis, 11 variables were associated with a risk of OM. When a Bonferroni correction was introduced, gender, prematurity, parity, maternal age, maternal self-estimated health, taking penicillin during pregnancy, and terminating breastfeeding before age six months, was associated with a risk of early OM. The adjusted ORs of OM for boys versus girls was 1.30 (95% CI 1.18–1.44). The OR having one sibling versus no siblings was 3.0 (95% CI 2.64–3.41). If the woman had been taking penicillin during pregnancy, the OR was 1.35 (95% CI 1.15–1.58). Children born before 38th gestational week had an increased OR for early OM of 1.49 (95% CI 1.21–1.82). Children of young women had an increased OR of early OM compared to children of older women. Additionally, children of women who rated their own health low compared to those rating their health as high, had an increased OR of 1.38 (95% CI 1.10–1.74). Finally, children being breastfeed less than 6 months, had an increased OR of 1.42 (95% CI 1.28–1.58) compared to children being breastfeed beyond 6 months.

Conclusion

These findings indicate that prenatal factors are of less importance regarding early OM before the age of six months. Postnatal risk factors seem to pose the main risk of early OM.

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<![CDATA[A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcef5

Background

Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting.

Methodology

We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1–15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%.

Findings

The mean age of participants was 9.5 years (S.D.3.1, range: 1–15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2–100) in the azithromycin group and 96.9% (95% CI: 94.1–99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9–64.9) in the azithromycin group and 49.1% (95% CI: 41.2–56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority.

Conclusions

A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular benzathine penicillin for the treatment of early yaws among Ghanaian patients, and provides additional support for the WHO policy for use of oral azithromycin for the eradication of yaws in resource-poor settings.

Trial Registration

Pan African Clinical Trials Registry PACTR2013030005181 http://www.pactr.org/

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