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OBJECTIVES: Penicillin allergies are the most commonly reported drug allergy. However, recent research has supported the concept that reported penicillin allergy does not equal true allergy. False penicillin allergies and associated alternative antibiotic use can result in inferior clinical outcomes. Determination of true versus self-reported allergy can be determined through skin testing to penicillin and oral challenge to amoxicillin. Penicillin allergy evaluations improve antibiotic utilization but penicillin skin testing (PST) requires more resources than oral amoxicillin challenge alone. Because amoxicillin challenge without preceding PST may be safe in low-risk patients, we assessed a risk stratification tool for outpatient penicillin allergy evaluations that stratify low-risk patients to receive amoxicillin challenge without prior skin testing. METHODS: The patient population was identified using the Massachusetts General Hospital Allergy Associates clinic schedule in EPIC from the beginning of January 2017 through the end of July 2018. Patients were classified into one of two evaluation methods based on allergy history, using the MGH Allergy Associates Outpatient Penicillin Allergy Pathway. Patients deemed low-risk were evaluated with direct 2-step oral amoxicillin challenge. Intermediate-risk patients were evaluated with PST and subsequent oral amoxicillin challenge. Skin testing (ST) was performed using epi-cutaneous prick tests with a major and minor determinate of penicillin, histamine (positive) and saline (negative) controls, followed by intradermal injections of the same reagents. ST was followed by one oral dose of 500mg amoxicillin. Direct oral challenge involved doses of 50mg of amoxicillin in the first step or 500mg of amoxicillin in the second step. These patients’ charts were retrospectively reviewed for information regarding the initial antibiotic allergic reaction, type of allergy testing administered, and outcomes of the outpatient allergy testing. Analysis was performed to assess and significant differences in patient characteristics, safety, and outcomes in patients given preceding skin testing or direct oral amoxicillin challenge. RESULTS: Overall, 509 eligible patients were reviewed. Four hundred twenty-six patients underwent PST with subsequent oral amoxicillin challenge. The remaining 83 patients received direct, two-step oral amoxicillin challenge. Across both groups, 43 adverse drug reactions (ADRs) were observed, 26 of which were considered hypersensitivity reactions (HSRs). The proportion of patients in each testing group that experienced ADRs was near equal, 8.5% of the skin tested group and 8.4% of the direct challenge group. One patient in each group had an HSR requiring treatment with epinephrine. Using multivariate logarithmic analysis to evaluate potential predictors for ADRs and HSRs, female sex was the only variable associated with significant increased odds for an ADR. There were no significant findings for increased odds for HSRs, including evaluation method with direct drug challenge. The proportion of patients considered to have a true penicillin allergy was similar in the two groups. DISCUSSION: PST is a vitally important aspect of antibiotic stewardship, especially when conducted before antibiotic treatment is required. Though the standard procedure is skin testing with penicillin, followed by oral amoxicillin challenge, direct oral challenges can be considered for appropriately selected low-risk patients presenting for penicillin allergy evaluation. PST is nonetheless advisable for patients with higher risk allergy histories, pregnant patients, and patients with tenuous cardiac or pulmonary status.

Staphylococcus aureus is the most clinically important Staphylococcus species and is associated with high mortality in patients with positive blood cultures. S. aureus bacteria may cause a variety of disease manifestations ranging from minor skin infections to life-threatening conditions such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome (TSS) and sepsis. This microorganism belonging to the gram positive cocci may also be part of the normal flora. In Sweden, penicillinase-stable penicillins are the primary alternatives to treat S. aureus infection. Mutations in genes encoding the penicillin binding proteins (PBP2) in the bacteria which lead to a lower affinity for the  beta-lactam antibiotics define  methicillin resistant S. aureus (MRSA) which is a significant global health problem. Other resistance mechanisms of S. aureus are present, and one of these is penicillinase production which is associated with resistance to penicillin G. In order to detect penicillinase production in S. aureus, there are several methods but the European guidelines recommend disc diffusion and the clover-leaf test for follow-up if the zone diameter for benzylpenicillin (PcG) is 26 mm or more. There are no modern Swedish studies on the prevalence of S. aureus susceptible to PcG and this has recently attained interest from infectious disease physicans. Thus, the purpose of this study was to investigate the frequency of S. aureus susceptible to PcG from blood cultures isolated during 2012 from the Kalmar county.    Disc diffusion testing showed that 32% of 90 unique isolates tested had an inhibition zone diameter of PcG that was ≥ 26 mm in diameter. All of these isolates were confirmed as PcG sensitive with clover-leaf test. Internal controls showed little variation and external control isolates showed full agreement with the results obtained from a Danish study, suggesting that PcG zone diameter of ≥ 26 mm in combination with cloverleaf test can be used to detect penicillin susceptibility of S. aureus.    In conclusion, this study shows that nearly 1 /3 of the blood culture isolates of S. aureus from Kalmar are sensitive to benzylpenicillin.

Thesis (Doctoral)--Technische Universität Carolo-Wilhelmina zu Braunschweig, 1983.

Thesis (Masters Diploma(Technology))--Cape Technikon, Cape Town, 2000 / Streptococcus pneumoniae (S.pneumoniae) infections are an important cause of morbidity and mortality in adults and children worldwide. Mortality rates are highest amongst the very young and the elderly. Streptococcus pneumoniae is the most common form of community acquired bacterial pneumonia. Other diseases commonly caused by Streptococcus pneumoniae include meningitis, pericarditis, bacteraemia and septicaemia. Penicillin is today still consid3red the drug of choice when treating pneumococcal infections. The emergence of resistant pneumococcal strains has made it necessary to adapt antimicrobial regimens when treating pneumococcal infections. Hansman (1967) reported the first penicillin resistant strain, which was isolated from a woman in Australia in 1967. Since then penicillin and multi-resistant Streptococcus pneumoniae strains have been observed worldwide, including South Africa. Streptococcus pneumoniae infections may be caused by anyone of the 84 serotypes recognized to date. The distribution of serotypes varies, depending on geographical area, age and site of infection. High-level penicillin resistance and multiple resistant Streptococcus pneumoniae strains have been recognised worldwide in a few pneumococcal serotypes. Pneumococcal vaccines have been used since the seventies. These capsular polysaccharide vaccines are generally recommended for at risk population such as the elderly and immunocompromised patients. This vaccine is not effective in children under 2 years old. The current vaccine in South Africa (Pneumovax, MSD) consists of purified capsular polysaccharides of 23 pneumococcal serotypes. Conjugated polysaccharide vaccines have been developed to overcome the problems of efficacy in children < 2 years old. These vaccines consist of a capsular polysaccharide linked to a protein carrier, which makes them immunogenic in infants. Clinical trials of these vaccines are currently under way to demonstrate safety, efficacy and immunogenicity. Knowledge of serotype distribution and antimicrobial susceptibility patterns are important in relation to the treatment of pneumococcal diseases and vaccination programmes.

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