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61. The Challenge of De-labeling Penicillin Allergy. Full Text available with Trip Pro

The Challenge of De-labeling Penicillin Allergy. Even though 8-25% of most populations studied globally are labeled as penicillin allergic, most diagnoses of penicillin allergy are made in childhood and relate to events that are either not allergic in nature, are low-risk for immediate hypersensitivity, or are a potential true allergy that has waned over time. Penicillin allergy labels directly impact antimicrobial stewardship by leading to use of less effective and broader spectrum (...) antimicrobials and are associated with antimicrobial resistance. They may also delay appropriate antimicrobial therapy, and lead to increased risk of specific adverse healthcare outcomes. Operationalizing penicillin allergy de-labeling into a new arm of antimicrobial stewardship programs (ASPs) has become an increasing global focus. We performed an evidence-based narrative review of the literature of penicillin allergy label carriage, the adverse effects of penicillin allergy labels and current approaches

2019 Allergy

62. Clinical prognoses of patients with a bloodstream infection caused by ampicillin-susceptible but penicillin-resistant <i>Enterococcus faecalis</i>: prospective observational study. Full Text available with Trip Pro

Clinical prognoses of patients with a bloodstream infection caused by ampicillin-susceptible but penicillin-resistant Enterococcus faecalis: prospective observational study. Introduction: To evaluate the clinical impacts of ampicillin-susceptible but penicillin-resistant (ASPR) phenotypes of Enterococcus faecalis on clinical outcomes in patients with a bloodstream infection (BSI).Methods: A total of 295 patients with an E. faecalis BSI from six sentinel hospitals during a two-year period (...) difference in survival was identified in a group of patients treated with ampicillin- and/or piperacillin-based regimens who were stratified according to the penicillin susceptibility of the causative pathogen (log-rank test, P = 0.011).Conclusions: ASPR E. faecalis BSIs resulted in a >2-fold higher 30-day mortality rate (26.9%, 18/67) than the BSIs caused by penicillin-susceptible strains (12.3%, 28/228). The differences in mortality rates of patients stratified by penicillin susceptibility were likely

2019 Antimicrobial Agents and Chemotherapy

63. Kinetic Profile and Molecular Dynamic Studies Show that Y229W Substitution in an NDM-1/L209F Variant Restores the Hydrolytic Activity of the Enzyme toward Penicillins, Cephalosporins, and Carbapenems. Full Text available with Trip Pro

Kinetic Profile and Molecular Dynamic Studies Show that Y229W Substitution in an NDM-1/L209F Variant Restores the Hydrolytic Activity of the Enzyme toward Penicillins, Cephalosporins, and Carbapenems. The New Delhi metallo-β-lactamase-1 (NDM-1) enzyme is the most common metallo-β-lactamase identified in many Gram-negative bacteria causing severe nosocomial infections. The aim of this study was to focus the attention on non-active-site residues L209 and Y229 of NDM-1 and to investigate

2019 Antimicrobial Agents and Chemotherapy

64. Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations. Full Text available with Trip Pro

Management of a surgical patient with a label of penicillin allergy: narrative review and consensus recommendations. Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems

2019 British Journal of Anaesthesia

65. Availability of benzathine penicillin G for syphilis treatment in Shandong Province, Eastern China. Full Text available with Trip Pro

Availability of benzathine penicillin G for syphilis treatment in Shandong Province, Eastern China. The shortage of benzathine penicillin G (BPG) worldwide presents a major challenge in the treatment of syphilis. Its availability for syphilis treatment has not been adequately evaluated in China.Two surveys were conducted among hospitals providing sexually transmitted infection clinical services in Shandong Province in 2012 and 2018. Data on the basic information and BPG availability

2019 BMC health services research

66. Determining the impact of Benzathine penicillin G prophylaxis in children with latent rheumatic heart disease (GOAL trial): Study protocol for a randomized controlled trial. (Abstract)

Determining the impact of Benzathine penicillin G prophylaxis in children with latent rheumatic heart disease (GOAL trial): Study protocol for a randomized controlled trial. Rheumatic heart disease (RHD) remains a high prevalence condition in low- and middle-income countries. Most individuals with RHD present late, missing the opportunity to benefit from secondary antibiotic prophylaxis. Echocardiographic screening can detect latent RHD, but the impact of secondary prophylaxis in screen (...) -detected individuals is not known.This trial aims to determine if secondary prophylaxis with every-4-week injectable Benzathine penicillin G (BPG) improves outcomes for children diagnosed with latent RHD. This is a randomized controlled trial in consenting children, aged 5 to 17 years in Northern Uganda, confirmed to have borderline RHD or mild definite RHD on echocardiography, according to the 2012 World Heart Federation criteria. Qualifying children will be randomized to every-4-week injectable

2019 American Heart Journal Controlled trial quality: predicted high

67. Safety of direct drug provocation testing in adults with penicillin allergy and association with health and economic benefits. (Abstract)

Safety of direct drug provocation testing in adults with penicillin allergy and association with health and economic benefits. Nonprescription of penicillin-containing antibiotics in patients diagnosed with penicillin allergy is associated with morbidity and mortality. Adverse reactions to penicillins comprise type A and B reactions.To assess the feasibility of penicillin allergy evaluation without penicillin skin testing (PST) for adult patients with type B reactions and the health (...) and economic benefits of this process.Inpatients at an Australian tertiary hospital between April 1, 2017, and April 30, 2018, with a diagnosis of type B penicillin allergy, requiring a penicillin-containing antibiotic for treatment, were included. All patients underwent clinical history review, PST, and drug provocation testing (DPT).Seventy-one patients were enrolled. Sixty-three reported a history of type B or unknown adverse reactions. No patients had a history of anaphylaxis requiring intubation

2019 Asthma & Immunology

68. Penicillin-binding protein typing, antibiotic resistance gene identification and molecular phylogenetic analysis of meropenem-resistant <i>Streptococcus pneumoniae</i> serotype 19A-CC3111 strains in Japan. Full Text available with Trip Pro

Penicillin-binding protein typing, antibiotic resistance gene identification and molecular phylogenetic analysis of meropenem-resistant Streptococcus pneumoniae serotype 19A-CC3111 strains in Japan. Since the introduction of pneumococcal conjugate vaccines, the prevalence of non-meropenem-susceptible pneumococci has been increasing in Japan. In an earlier study, we demonstrated that the multidrug-resistant serotype 15A-ST63 in Japan has a specific pbp1a sequence (pbp1a--13) that could (...) acquisition of pbp1a-13 seemed to cause only penicillin resistance and not multidrug resistance; a combination of PBP recombination in the pbp2b and/or pbp2x region(s) with acquisition of pbp1a-13 caused multidrug resistance. Conserved amino acid motif analysis suggested that the pbp1a 370SXXK, pbp2b 448SXN and pbp2x 337SXXN motifs were the candidates for amino acid substitutions increasing the MICs of meropenem, cefotaxime and penicillin. We identified a specific clone that was correlated with multidrug

2019 Antimicrobial Agents and Chemotherapy

69. Endocarditis Caused by Highly Penicillin-Resistant Viridans Group Streptococci: Still Room for Vancomycin-Based Regimens. Full Text available with Trip Pro

Endocarditis Caused by Highly Penicillin-Resistant Viridans Group Streptococci: Still Room for Vancomycin-Based Regimens. Introduction: Optimal treatment options remain unknown for infective endocarditis (IE) caused by penicillin (PEN)-resistant viridans group streptococcal (VGS) strains. The aims of this study were to report two cases of highly-PEN-resistant-VGS-IE, perform a literature review, and to evaluate various antibiotic combinations in vitro and in vivoMaterials and Methods

2019 Antimicrobial Agents and Chemotherapy

70. Is direct oral amoxicillin challenge a viable approach for 'low-risk' patients labelled with penicillin allergy? Full Text available with Trip Pro

Is direct oral amoxicillin challenge a viable approach for 'low-risk' patients labelled with penicillin allergy? Spurious penicillin allergy (PenA) is a major public health problem. Up to 10% of the population and 20% of inpatients are labelled with PenA, but only <5%-10% have a proven allergy following comprehensive investigations. PenA tests are labour intensive and require specialist input, which may not be readily available due to limited allergy services. Therefore, patients with PenA

2019 Journal of Antimicrobial Chemotherapy

71. Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts. Full Text available with Trip Pro

Adherence to antibiotic guidelines and reported penicillin allergy: pooled cohort data on prescribing and allergy documentation from two English National Health Service (NHS) trusts. To investigate documentation of antimicrobial allergy and to determine prescribing adherence to local antibiotic guidelines for inpatients with and without reported penicillin allergy treated for infection in a National Health Service (NHS) context.Data were collected at two English hospital NHS trusts over two (...) as adjusted ORs.A total of 1497 patients were included, with 2645 antibiotics orders. Patients were treated for CAP (n=495; 33.1%), UTI (407; 27.2%), HAP (330; 22%) and SSTI (265; 17.7%). There were 240 (16%) patients with penicillin allergy. Penicillin allergy was recorded as allergy (n=52; 21.7%), side effect (27; 11.3%) and no documentation (161; 67.1%). Overall, 2184 (82.6%) antibiotic orders were guideline-adherent. Adherence was greatest for those labelled penicillin allergy (453 of 517; 87.6

2019 BMJ open

72. Evaluation of a pharmacist-led penicillin allergy de-labelling ward round: a novel antimicrobial stewardship intervention. (Abstract)

Evaluation of a pharmacist-led penicillin allergy de-labelling ward round: a novel antimicrobial stewardship intervention. Antibiotic allergy labels (AALs), reported by up to 25% of hospitalized patients, are a significant barrier to appropriate prescribing and a focus of antimicrobial stewardship (AMS) programmes.A prospective audit of a pharmacist-led AMS penicillin allergy de-labelling ward round at Austin Health (Melbourne, Australia) was evaluated. Eligible inpatients with a documented (...) penicillin allergy receiving an antibiotic were identified via an electronic medical report and then reviewed by a pharmacist-led AMS team. The audit outcomes evaluated were: (i) AMS post-prescription review recommendations; (ii) direct de-labelling; (iii) inpatient oral rechallenge referral; (iv) skin prick testing/intradermal testing referral; and (v) outpatient antibiotic allergy clinic assessment.Across a 5 month period, 106 patients were identified from a real-time electronic prescribing antibiotic

2019 Journal of Antimicrobial Chemotherapy

73. Efficacy of high doses of penicillin versus amoxicillin in the treatment of uncomplicated community acquired pneumonia in adults. A non-inferiority controlled clinical trial. Full Text available with Trip Pro

Efficacy of high doses of penicillin versus amoxicillin in the treatment of uncomplicated community acquired pneumonia in adults. A non-inferiority controlled clinical trial. Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries.To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAP.Multicentre, parallel, double-blind, controlled, randomized clinical trial.31 primary care centers (...) in Spain.Patients from 18 to 75 years of age with no significant associated comorbidity and with symptoms of lower respiratory tract infection and radiological confirmation of CAP were randomized to receive either penicillin V 1.6 million units, or amoxicillin 1000mg three times per day for 10 days.The main outcome was clinical cure at 14 days, and the primary hypothesis was that penicillin V would be non-inferior to amoxicillin with regard to this outcome, with a margin of 15% for the difference in proportions

2019 Atencion Primaria Controlled trial quality: predicted high

74. Implementation of a pharmacist-led penicillin allergy de-labelling service in a public hospital. (Abstract)

Implementation of a pharmacist-led penicillin allergy de-labelling service in a public hospital. Inaccurate allergy labelling results in inappropriate antimicrobial management of the patient, which may affect clinical outcome, increase the risk of adverse events and increase costs. Inappropriate use of alternative antibiotics has implications for antimicrobial stewardship programmes and microbial resistance.All adult inpatients labelled as penicillin allergic were identified and screened (...) for eligibility by the study pharmacist. An accurate allergy and medication history was taken. Patients were 'de-labelled', underwent oral challenge or were referred to an immunology clinic, if study criteria were met. All patients included in the study were followed-up 1 year after intervention.Two hundred and fifty eligible patients with a label of 'penicillin allergy' were identified. The prevalence of reported penicillin allergy at Middlemore Hospital was 11%. We found that 80% of study patients could

2019 Journal of Antimicrobial Chemotherapy

75. <i>In Vitro</i> Activity of Tebipenem (SPR859) Against Penicillin-Binding Proteins of Gram-negative and Gram-positive Bacteria. Full Text available with Trip Pro

In Vitro Activity of Tebipenem (SPR859) Against Penicillin-Binding Proteins of Gram-negative and Gram-positive Bacteria. Tebipenem (SPR859) is the microbiologically active form of SPR994, tebipenem-pivoxil, an orally available carbapenem with activity against extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae Measurement of the relative binding of SPR859 to the bacterial cell targets revealed that it is a potent inhibitor of multiple penicillin-binding proteins (PBPs

2019 Antimicrobial Agents and Chemotherapy

76. Relatively high rates of cefotaxime- and ceftriaxone-non-susceptible isolates among group B streptococci with reduced penicillin susceptibility (PRGBS) in Japan. (Abstract)

Relatively high rates of cefotaxime- and ceftriaxone-non-susceptible isolates among group B streptococci with reduced penicillin susceptibility (PRGBS) in Japan. We have previously identified group B Streptococcus (GBS) clinical isolates with reduced penicillin susceptibility (PRGBS) that were non-susceptible to cefotaxime; however, the rates of cefotaxime and ceftriaxone non-susceptibility among PRGBS isolates have never been reported. Therefore, we first determined the MICs of 22 (...) antibacterial drugs/compounds for 74 PRGBS isolates and then determined the rates of cefotaxime and ceftriaxone non-susceptibility among these isolates.We used 74 clinical PRGBS isolates, previously collected in Japan and confirmed to harbour relevant amino acid substitutions in PBP2X. We also used 80 penicillin-susceptible GBS (PSGBS) clinical isolates as controls. The MICs of 22 antibacterial drugs/compounds for all 154 GBS isolates were determined via microdilution and/or agar dilution methods

2019 Journal of Antimicrobial Chemotherapy

77. Direct oral amoxicillin challenge without preliminary skin testing in adult patients with allergy and at low risk with reported penicillin allergy. (Abstract)

Direct oral amoxicillin challenge without preliminary skin testing in adult patients with allergy and at low risk with reported penicillin allergy. Introduction: Ten percent of hospitalized patients report penicillin allergy; however, recent studies indicate that ∼98% of these patients are not acutely hypersensitive. Unconfirmed penicillin allergy poses public health risks, and an evaluation of penicillin allergy labels is recommended to improve antibiotic stewardship. Although the most widely (...) accepted protocol is penicillin skin testing, followed by oral amoxicillin challenge, time constraints and resources may preclude this. Recent literature supports the safety and efficacy of direct oral amoxicillin challenge in individuals at low risk. Methods: We retrospectively evaluated direct oral challenge acceptance and outcomes in eligible adult outpatients with allergy and with a penicillin allergy label over a 6-month period. Direct oral amoxicillin challenge was recommended in patients

2019 Allergy and Asthma Proceedings

78. The Effect of Non-penicillin Antibiotic Regimens on Neonatal Outcomes in Preterm Premature Rupture of Membranes. Full Text available with Trip Pro

The Effect of Non-penicillin Antibiotic Regimens on Neonatal Outcomes in Preterm Premature Rupture of Membranes. Objective  A 7-day course of a penicillin (PCN) and macrolide is standard of care (SAR) in preterm premature rupture of membranes (PPROM). Data regarding alternative antibiotic regimens are limited. We sought to assess the impact of non-PCN regimens on neonatal outcomes. Study Design  Secondary analysis of randomized controlled trial of antenatal magnesium sulfate. Singleton

2019 AJP Reports Controlled trial quality: predicted high

79. Clinical and Economic Outcomes of Penicillin Skin Testing as an Antimicrobial Stewardship Initiative in a Community Health System. Full Text available with Trip Pro

Clinical and Economic Outcomes of Penicillin Skin Testing as an Antimicrobial Stewardship Initiative in a Community Health System. Penicillin skin testing (PST) is a novel way to reduce the use of broad-spectrum agents in penicillin-allergic patients. This study evaluated the outcomes of patients with antimicrobials prescribed with and without PST in a community health system.We performed a quasi-experimental study that compared an intervention group of 100 patients who completed PST over (...) an open enrollment period beginning January 2016 with a matched control group of 100 patients who were penicillin allergic. Patients in the control group were matched to infection diagnosis codes of members of the PST group and randomly selected and matched on a 1:1 basis. The primary outcome was noncarbapenem beta-lactam days of therapy (DOT). The secondary outcome assessed the average cost of antimicrobial therapy for the intervention group before and after PST.Seventy of the 98 patients (71%) who

2019 Open forum infectious diseases Controlled trial quality: uncertain

80. Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial. Full Text available with Trip Pro

Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial. Penicillin G Benzathine (PGB) is the cornerstone of syphilis treatment. However, its intramuscular (IM) administration is associated with pain at the site of injection. The dilution of PGB with local anesthetics is recommended in some guidelines, but the evidence that supports it, particularly in adults and in HIV infection, is scarce

2019 BMC Infectious Diseases

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