Penicillin In Patients Research Articles

The impact of Post-Transplant doxycycline in AL amyloidosis – updated results after Long-Term follow up

Introduction The current treatment paradigm of AL amyloidosis lacks effective fibril-directed therapies. Doxycycline has been shown to have anti-fibril properties in preclinical models. In 2012, we reported that posttransplant prophylaxis with doxycycline was associated with improved survival compared to penicillin in patients with haematologic response. We provide here updated results after long-term follow up. Methods We included 553 patients who underwent transplant between July 24th, 1996, and June 24th, 2014. Doxycycline 100 mg daily was used for prophylaxis in patients with penicillin allergy; since 2013, doxycycline was used as the standard for prophylaxis. Prophylaxis was typically continued for a year after transplant. Results The median follow-up from transplant was 12.7 years. Doxycycline was used for prophylaxis in 33% of patients; the rest received penicillin. The median time to next treatment was 6.0 (95%CI; 4.4–8.8) years and 6.0 (95%CI; 4.9–7.1) years in the doxycycline and penicillin groups, respectively (p = .89). The median overall survival was 12.0 (95%CI: 11.0–19.6) years and 11.0 (95%CI: 9.6–12.7) years in the 2 groups, respectively (p = .17). There was a minimal trend towards improved survival with doxycycline among patients with ≥ very good partial response and among patients with organ response that was not statistically significant. Conclusion After long-term follow-up, there is no clear evidence to support benefit of doxycycline in the post-transplant setting.

O04 A systematic review of the effect of therapeutic drug monitoring on patient health outcomes during treatment with penicillins

BackgroundDosing regimens guided by therapeutic drug monitoring (TDM) may be able to improve penicillin exposure in patients. Improved penicillin exposure could result in improved patient health outcomes. This systematic review aims to describe the impact TDM in penicillin treatment has on health outcomes, including the emergence of antimicrobial resistance (AMR).MethodsA search of four databases was conducted and supplemented with a hand search of the literature. Studies that measured concentrations of penicillins in patients, adjusted dosing regimens according to the result and reported health outcomes were selected. The risk of bias was assessed according to study type: randomized controlled trials (RCTs) were assessed with the revised Cochrane risk-of-bias tool for randomized trials (RoB2) assessment tool, the risk of bias in non-randomized studies (ROBINS-1) assessment tool was used to assess observational studies, and the Office of Health Assessment and Translation (OHAT) tool was used to assess case studies. The study characteristics were tabulated and described using a narrative synthesis.ResultsThree RCTs, 16 observational cohort studies and 9 case studies were included. None of the studies showed statistically significant improvements in health outcomes, when comparing groups receiving TDM and standard care. Five observational studies showed improvement in at least one health outcome statistically significantly associated with target attainment: mortality,1–5 bacterial persistence,1,4,5 ICU length of stay,4 treatment efficacy,1,4,6 and suppression of AMR.4 However there was a high risk of bias in all of these studies for health outcomes. Most had pharmacological primary outcomes and were underpowered to detect health outcomes. All three RCTs and four (25%) observational studies found that the use of penicillin TDM was associated with improved pharmacological target attainment. Only one study was found that assessed the impact of β-lactams TDM on AMR and found that target attainment of 100% ƒT>4×MIC was significantly associated with suppression of resistance. No studies found a detrimental effect of penicillin TDM on health outcomes. A meta-analysis was not performed due to the heterogeneity of the included studies.ConclusionsThere is little evidence to suggest that TDM improves health outcomes, however neither health outcomes nor reductions in emergence of AMR were adequately addressed by currently published studies. The evaluation of health outcomes was not the primary aim of the majority of the included studies, consequently those that did include these outcomes were underpowered to detect a difference. Observational studies often did not take into account co-interventions, or confounding factors, resulting in a high risk of bias. Large variations in how TDM of penicillins was implemented and the different populations used meant that a quantitative synthesis of results was not suitable. Recommendations to standardize penicillin TDM are a challenge currently, as there is no clear evidence of optimal conditions. Suitably powered studies designed to assess clinical outcomes are required to resolve the ambiguity surrounding the impacts of TDM on clinical outcomes, and to address the gap of the impacts on AMR. Further, appropriate standardized protocols and concentration targets for penicillin TDM in humans need to be identified for it to be implemented successfully.

The diagnosis of non-life-threatening immediate penicillin allergy should not rest upon low sIgE results between 0.10 kUA/L and 0.35 kUA/L in isolation

Uncertainties remain about the optimal decision threshold for sIgE results in patients with a penicillin allergy. Historically, the cut-off for sIgE results has been set at 0.35 kUA/L, but recently it has been suggested that lowering the threshold to 0.10 kUA/L could improve diagnosis. This study aims to assess the clinical relevance of low sIgE values between 0.10 and 0.35 kUA/L for penicillins in patients who experienced immediate reactions to amoxicillin (AmX), amoxicillin-clavulanic acid (AmC), or a non-specified penicillin and demonstrating negative skin testing.

Differences in Gut Microbiome in Hospitalized Immunocompetent vs. Immunocompromised Children, Including Those With Sickle Cell Disease.

Background: Gut microbial diversity and composition play important roles in health. This cross-sectional study was designed to test the hypothesis that hospitalized children who may be relatively immunocompromised (IC), defined as those with cancer, sickle cell disease (SCD), transplantation, or receiving immunosuppressive therapy) would have decreased microbial diversity, increased Clostridioides difficile colonization and different species composition compared to non-immunocompromised (Non-IC) children admitted to the same pediatric unit.Methods: A stool sample was obtained within 72 h of admission to a single unit at The Children's Hospital at Montefiore, Bronx, NY from March 2016 to February 2017 and the microbiome assessed by 16S rRNA sequencing. C. difficile colonization was assessed by glutamate dehydrogenase antigen and toxin polymerase chain reaction assays.Results: Stool samples were obtained from 69 IC (32 SCD, 19 cancer, 9 transplantation and 9 other) and 37 Non-IC patients. There were no significant differences in microbial alpha diversity and C. difficile colonization comparing IC vs. non-IC patients. Lower alpha diversity, however, was independently associated with the use of proton pump inhibitors or antibiotics, including prophylactic penicillin in patients with SCD. Differences in specific species abundances were observed when comparing IC vs. non-IC patients, particularly children with SCD. Non-IC patients had increased abundance of commensals associated with health including Alistipes putredinis, Alistipes ihumii, Roseburia inulinivorans, Roseburia intestinalis, and Ruminococcus albus (p < 0.005).Conclusions: Antibiotics and proton pump inhibitors, which were more commonly used in IC children, were identified as risk factors for lower microbial diversity. Non-IC patients had higher abundance of several bacterial species associated with health. Longitudinal studies are needed to determine the clinical significance of these differences in gut microbiome.

Is a positive intracutaneous test induced by penicillin mediated by histamine? A cutaneous microdialysis study in penicillin-allergic patients

BackgroundDiagnostic workup of penicillin allergy comprises skin testing with penicillins, and patients are deemed allergic if skin test is positive. However, the literature suggests that skin test-positive patients may be challenge-negative, indicating that the skin test may be falsely positive.ObjectiveTo investigate real-time histamine release from a positive intracutaneous test induced by penicillin in patients with positive and negative challenges to penicillin.MethodsSkin microdialysis was performed in 21 penicillin-allergic patients with positive skin test, 13 non-allergic volunteers serving as negative controls, and 7 grass pollen-allergic patients serving as positive controls. Histamine was measured by microdialysis after skin test with penicillin/grass/NaCl. Penicillin challenge was subsequently performed in 12 of the patients.ResultsOnly 10/21 patients (47.6%) were skin test positive at microdialysis. During microdialysis 13 single intracutaneous tests were positive and histamine was detected in 4/13 occurring in four challenge positive patients. Thirteen/21 patients (61.9%) were deemed allergic to penicillin; eight had positive skin test. Two patients with positive skin test were challenge negative. In grass pollen allergic patients, 7/7 had a positive intracutaneous test to grass and all released histamine in the wheals. All 13 negative controls had negative intracutaneous test to penicillin and no histamine release.ConclusionHistamine was only detected in the minority of positive intracutaneous tests with penicillin in penicillin-allergic patients. Other mediators may be involved.

Variation in Reporting of Penicillin Allergy and its Consequences: an Evaluation of 13 Hospitals

BackgroundPenicillin allergy is the most common antibiotic allergy noted within medical records, and its inaccurate reporting leads to increased use of alternative antibiotics that may be less effective, broader in spectrum, more toxic, and costly.MethodsWe retrospectively reviewed the reported allergies to penicillin in patients cared for at 13 hospitals within one health system over a 3 month period (June-August 2016). The data were abstracted from the electronic medical records on penicillin allergy status for both inpatient and outpatient visits. Hospitals were compared on their use of systemic antibiotics for inpatients. The proportions of total defined daily doses (DDD) for quinolones, aztreonam, carbapenems, cephalosporins, and penicillins were compared. Spearman’s rank and Pearson’s correlation were used to evaluate the strength of the relation between increased penicillin allergy reported and the use of the different antibiotic classes.Results23,290 of 169,912 (13.7%; range 8%–20%) patients from 13 hospitals were reported penicillin allergic. There was a strong correlation between the proportion of patients with penicillin allergy and quinolone use (rho=0.77; P = 0.002; Figure 1), cephalosporins excluding fourth-generation (r=0.70; P = 0.007; Figure 2), and a weaker correlation with carbapenem use (rho=0.52; P = 0.168) and aztreonam (r=0.53; P = 0.06). On the other hand, penicillins had a moderate negative correlation (r=-0.58; P = 0.036; Figure 3), and extended spectrum penicillins had a strong negative correlation (r=-0.72; P < 0.005). Fourth-generation cephalosporin use did not correlate with the penicillin allergy rate (rho=-0.03; P = 0.92).ConclusionReported penicillin allergy varies between hospitals and higher reported allergy is associated with more quinolone and cephalosporin use, and less use of penicillin-based regimens. Adequate documentation of penicillin allergy may promote the choice of more optimal regimens when treating patients.Disclosures All authors: No reported disclosures.

Risk of Allergic Reactions to Recurrent Intravenous Penicillin Administration in Penicillin Skin Test Negative Patients

Patients with a history of penicillin allergy who are found to be skin test negative to penicillin are able to tolerate repeated oral doses of penicillin with low rates of resensitization. However, the resensitization rate after repeated doses of intravenous penicillin is less clear. We sought to evaluate the risk of allergic reactions to repeated doses of intravenous penicillin in patients who previously reported penicillin allergy and were found to be penicillin skin test and oral challenge negative. A retrospective review was conducted between 2010 and 2016 of adult patients who were treated at our academically affiliated hospitals. Patients included in the review had negative penicillin allergy testing and were treated with 2 or more courses of intravenous penicillins. Charts were evaluated to identify any adverse drug reactions. Thirty-two patients met our inclusion criteria. The index penicillin-associated reactions ranged from rash to hypotension and were, for the most part, remote as 75% had reported reactions more than 10 years previously. More than 50% of patients received 3 or more courses of intravenous penicillins. The most frequently repeated intravenous penicillin overall was piperacillin/tazobactam. Thirty-two patients received a total of 111 courses of intravenous penicillins and none developed an immediate hypersensitivity reaction. In patients who report penicillin allergy and have negative penicillin allergy testing, repeated administration of intravenous penicillin antibiotics appears to be safe. Larger prospective studies should be performed to confirm these observations.

Penicillin skin testing as an antimicrobial stewardship initiative

An initiative to determine the effects of penicillin skin testing (PST) from an antimicrobial stewardship perspective is described. Penicillin allergy is one of the most frequently reported allergies; however, only about 10% of self-reports of penicillin allergy are accurate. Incorrect penicillin allergies are therefore a significant barrier to antimicrobial stewardship, with important clinical and economic implications, including increased antimicrobial resistance, an increased overall cost of care, increased length of stay, and, ultimately, increased mortality. As part of its antimicrobial stewardship program, a community health system launched a PST initiative in order to optimize therapy, reduce adverse events acquisition costs, and minimize development of antibiotic resistance. The PST program involves the use of a standardized protocol for the assessment of hypersensitivity to penicillin in patients with suspected penicillin allergy. Among 36 patients who completed the PST protocol during an eight-month period, all had a negative result; in 27 of those patients, a conversion of antimicrobial therapy to a penicillin or cephalosporin was implemented as a direct result of PST. In patients with a self-reported penicillin allergy, PST led to a reduction in the use of carbapenems, aztreonam, vancomycin, and other broad-spectrum agents within a health system. A decrease in drug costs was documented in a sample of patients switched to a penicillin or a cephalosporin after PST.

Phenotypic and Genotypic Characteristics of Listeria monocytogenes Isolated From Dairy and Meat Products

Background: Listeria monocytogenes is a foodborne pathogen and a serious threat to the public health in the world. Consumption of traditional foods such as dairy and meat products can be a major reason for relative abundance and isolation of these bacteria. Objectives: The purpose of this study was to determine the phenotypic and genotypic characteristics of L. monocytogenes strains isolated from dairy and meat products. Materials and Methods: A total of 317 dairy products and meat-processed samples were collected. Antibiotic susceptibility test was performed on each sample by the disk diffusion method (Kirby Bauer). Five reference loci were used for typing of L. monocytogenes strains by MLVA (Multiple Locus VNTR Analysis) Technique. Results: A total of 24 L. monocytogenes isolates were collected from the dairy and meat products. Resistance of isolated L. monocytogenes strains to penicillin G were 54.54% (from dairy products) and 46.15% (from processed meat). Genetic relatedness of isolates were assessed by MLVA. Out of 13 different types, type 2 with 6 strains and type 3 with 4 strains, were the most common types. Conclusions: MLVA analysis showed that samples obtained from different sources could have similar genetic profile. As a result, administration of penicillin in patients with listeriosis (especially pregnant women) and antibiotic susceptibility test are recommended. The fast and accurate methods such as MLVA for tracking of pollution sources of L. monocytogenes are recommended during outbreaks.

Physician approaches to beta-lactam use in patients with penicillin hypersensitivity

Beta-lactam antibiotics are widely used, but hypersensitivity reactions are common and difficult to manage. This study was designed to identify lack of knowledge regarding the safe use of alternative beta-lactams in penicillin-allergic patients and assess management differences between allergists and nonallergists. An electronic physician survey was sent to 623 providers in allergy, internal medicine, pediatrics, and family medicine, querying beta-lactam use in patients with a history of penicillin allergy. A total of 110 (17.7%) surveys were completed. For patients with a prior maculopapular rash to penicillin, most providers were uncomfortable prescribing penicillins again, although they would use other beta-lactams. In patients with an exfoliative dermatitis to penicillin, 46% of responders would not prescribe any beta-lactam again. For patients with a positive skin test to penicillin, only 45.1% of nonallergists were comfortable prescribing monobactams versus 62.5% of allergists; 30.3% of all responders would give a carbapenem. In patients with urticaria to penicillin, pediatricians were the most comfortable prescribing third- or fourth-generation cephalosporins. Providers (both allergists and nonallergists) were unfamiliar with the safety of prescribing penicillin in patients with history of maculopapular rash, the safety of monobactams, and low cross-reactivity with carbapenems in penicillin-allergic individuals. Nonallergists were also unfamiliar with the usefulness of penicillin skin testing. Improved education is needed to address these areas. Additionally, we found variability in responses regarding exfoliative dermatitis and comfort prescribing cephalosporins in patients with suspected IgE-mediated drug allergy to penicillin, highlighting the need for additional research in these areas.

Leptospirosis-associated acute kidney injury: penicillin at the late stage is still controversial

Some antimicrobial agents are active in vitro against Leptospiras. The use of penicillins at the late stage of leptospirosis is still controversial. We aimed to evaluate the use of penicillin in patients with leptospirosis-associated acute kidney injury (AKI). A retrospective study was conducted of patients with leptospirosis admitted to two hospitals in Fortaleza city, Brazil, between 1985 and 2008. AKI was defined according to the RIFLE and AKIN classifications. Patients were divided in two groups according to whether they were treated with a penicillin or not. Two hundred and eighty-seven patients were included, with an average age of 36·8±15·6 years and mostly male (80·8%). One hundred and twelve patients (39%) received a penicillin. Patients treated with a penicillin were younger (32±14 years vs. 39±16 years, P=0·0002) and had a shorter hospital stay (8·4±5·0 vs. 11±7·7 days, P<0·0001). There was no difference in the onset of symptoms before hospital admission between the two groups (6·5±3·0 vs. 7·7±4·7, P=0·33). Systolic blood pressure was lower in the penicillin group (111±21 vs. 119±22 mmHg, P=0·04). AKI, need of dialysis and renal recovery at the time of hospital discharge were more frequent in patients who did not use a penicillin (P<0·05). Mortality was similar in both groups (11·6% vs. 13·7%, P=0·60). Treatment of leptospirosis with antibiotics, including the penicillin, remains controversial. The main benefit of using penicillin in the present study was a reduction in the length of hospital stay and fewer complications, such as AKI, but its use was not associated with a decrease in mortality. On balance of risks and benefits, we recommend the use of penicillin in late-stage leptospirosis.

A qualitative study of perceptions of using prophylactic penicillin in patients with sickle cell disease

Mina Abedian and colleagues examine why patients do not necessarily comply with prescribed regimens even when they understand the benefits

Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins

Skin test sensitivity in patients with immediate allergy to penicillins tends to decrease over time, but no information is available concerning in vitro tests. We analysed the negativization rates of two in vitro methods that determine specific immunoglobulin E (IgE) antibodies, the basophil activation test using flow cytometry (BAT) and the radioallergosorbent test (RAST), in immediate allergic reactions to penicillins. Forty-one patients with immediate allergic reactions to amoxicillin were followed up over a 4-year period. BAT and RAST were performed at 6-month intervals. Patients were randomized into groups: Group I, skin tests carried out at regular intervals; Group II, skin tests made only at the beginning of the study. Differences were observed between RAST and BAT (P < 0.01), the latter showing earlier negativization. Considering different haptens, significant differences for the rate of negativization were only found for amoxicillin (P < 0.05). Comparisons between Groups I (n = 10) and II (n = 31) showed a tendency to become negative later in Group I with RAST. Levels of specific IgE antibodies tended to decrease over time in patients with immediate allergic reactions to amoxicillin. Conversion to negative took longer for the RAST assay, although the differences were only detected with the amoxicillin hapten. Skin testing influenced the rate of negativization of the RAST assay, contributing to maintenance of in vitro sensitivity. Because of the loss of sensitivity over time, the determination of specific IgE antibodies to penicillins in patients with immediate allergic reactions must be done as soon as possible after the reaction.

P2102 Pre-admission penicillin in patients with meningitis or meningococcal disease

P2102 Pre-admission penicillin in patients with meningitis or meningococcal disease

Re-prescription of penicillin in patients who have had allergic-like reactions: Investigation using a large electronic medical record

Rationale To determine the frequency of re-prescription of penicillin to penicillin-allergic individuals and the risk of a second reaction in those who had a previous reaction. Methods A retrospective cohort study was conducted within the UK General Practice Research Database, an electronic medical record. All patients who had received a prescription for penicillin, 1987 through 9/2001, and those who had received a second prescription for a penicillin at least 60 days later, were selected. Patients with events consistent with a hypersensitivity (allergic-like) reaction within 30 days after the first prescription were compared to those without such events. Results 3,375,162 patients received at least one prescription for penicillin. Of 6212(0.18%) who experienced an allergic-like reaction to the initial penicillin prescription, 48.5% were given a second prescription for penicillin, compared with 59.8% of those without an initial allergic reaction (OR 0.6, 95% CI 0.6, 0.7). 2,017,957 patients were given two or more prescriptions for penicillin. 3014 (0.15%) experienced an allergic-like reaction with the first prescription and 57 (1.89%) of those had another reaction after the second prescription. The unadjusted OR of an allergic-like reaction with the second prescription for those who experienced an allergic-like reaction following the first prescription, compared with those who had no initial reaction, was 11.2 (95% CI 8.6, 14.6). Adjusting for confounding had no substantive effect on this result. Conclusions The risk of an allergic-like reaction to penicillin is markedly increased in those who have had a prior event. Re-prescription of penicillin to such patients is more frequent than anticipated.

Intramuscular penicillin is more effective than oral penicillin in secondary prevention of rheumatic fever--a systematic review.

People with a history of rheumatic fever (RF) are at high risk of recurrent attacks and of developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of RF and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin. To assess the effects of different penicillin regimens and formulations for preventing streptococcal infection and RF recurrence. We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), Medline (January 1966-July 2000), Embase (January 1985-July 2000), reference lists of articles, and contacted experts in the field. Randomised and quasi-randomised studies comparing: (i) oral with intramuscular penicillin; and (ii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous RF. Two reviewers independently assessed trial quality and extracted data. Six studies were included (1,707 patients). Data were not pooled because of clinical and methodological heterogeneity of the trials. Four trials (1,098 patients) compared intramuscular with oral penicillin and all showed that intramuscular penicillin was more effective in reducing RF recurrence and streptococcal throat infections than oral penicillin. One trial (360 patients) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every 2 weeks was better at reducing RF recurrence (relative risk (RR) 0.52, 95% confidence interval (CI): 0.33-0.83) and streptococcal throat infections (RR 0.60, 95% CI: 0.42-0.85). One trial (249 patients) showed that 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI: 0.48-0.92) compared with 4-weekly intramuscular penicillin. Intramuscular penicillin seemed to be more effective than oral penicillin in preventing RF recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor-quality trials and the use of outdated formulations of oral penicillin.

Moxifloxacino frente a amoxicilina en el tratamiento de la neumonía adquirida en la comunidad en América Latina. Resultados de un ensayo clínico multicéntrico

Since community-acquired pneumonia (CAP) is a common disease with a high morbidity rate, it is important to obtain information concerning its etiology and susceptibility to antibiotics across different geographic areas. This study presents data obtained in 5 Latin American counties in the course of an international clinical trial that evaluated the efficacy and safety of treatment with either moxifloxacin or amoxicillin administered for 10 days to patients suspected of having CAP caused by a pneumococcal infection. Details are given of the pathogens identified, the patterns of sensitivity to antibiotics observed, and the clinical and microbiological results obtained.A total of 84 patients were studied, of whom 70 (83.3%) were evaluated at the end of the trial to determine the efficacy and safety of the treatment received. Gram-positive bacteria were found in samples from 29 patients (80.5%). The pathogen was Streptococcus pneumoniae in 28 of those cases (77.7%). Gram-negative bacteria were found in 7 patients (19.4%), the most common being Haemophilus influenzae in 3 patients (8.3%). The presence of atypical microorganisms was detected in 18 of the 70 patients (25%), mainly Mycobacterium pneumoniae (n=11), and in 6 cases (8.5%) the infection was mixed. Ten strains of S. pneumoniae (35.7%) were shown to be susceptible to penicillin, 2 (7.1%) were highly resistant, and 16 (57.1%) showed moderate resistance. The clinical success rate at the final visit after treatment was 94.1% for moxifloxacin and 91.7% for amoxicillin. The results of this trial demonstrate a high prevalence of S. pneumoniae with reduced susceptibility to penicillin in patients with CAP in Latin America. It also revealed a high incidence of atypical pathogens and mixed infection in 8.6% of patients. This information should be taken into account when establishing protocols for empirical treatment of CAP in Latin America.

Penicillin for secondary prevention of rheumatic fever.

People with a history of rheumatic fever are at high risk of recurrent attacks of rheumatic fever and developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of rheumatic fever and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin. To assess the effects of penicillin compared to placebo and the effects of different penicillin regimens and formulations for preventing streptococcal infection and rheumatic fever recurrence. We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE (1997 to July 2000), EMBASE (1998 to July 2000), reference lists of articles and we contacted experts in the field. Randomised and quasi-randomised studies comparing (i) penicillin with control, (ii) oral with intramuscular penicillin (iii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous rheumatic fever. Two reviewers independently assessed trial quality and extracted data. Nine studies were included (n=3008). Data were not pooled because of heterogeneity. Overall, the methodological quality of included studies was poor. Three trials (n= 1301) compared penicillin with control. Only one of three studies showed that penicillin reduced rheumatic fever recurrence (RR 0.45, 95% CI 0.22 to 0.92) and streptococcal throat infection (RR 0.84, 95% CI 0.72 to 0.97). Four trials (n=1098) compared intramuscular with oral penicillin and all showed that intramuscular penicillin reduced rheumatic fever recurrence and streptococcal throat infections compared to oral penicillin. One trial (n= 360) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every two-weeks was better at reducing rheumatic fever recurrence (RR 0.52, 95% CI 0.33 to 0.83) and streptococcal throat infections (RR 0.60, 95% CI 0.42 to 0.85). One trial (n= 249) showed 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI 0.48 to 0.92) compared to 4-weekly intramuscular penicillin. Intramuscular penicillin seemed to be more effective than oral penicillin in preventing rheumatic fever recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor quality of trials.

Knowledge of pneumococcal resistance rates in Spain by family doctors

To know the knowledge of Spanish physicians related to pneumococcal resistance rates in an a country known to be one of the places with higher pneumococcal resistance rates and to know as well the choice of antibiotics in cases of suspected high penicillin-resistant pneumococcal pneumonia. A cross-sectional survey was set out in November during the Spanish Conference on Medicine Family held in Donosti (Basque). All the participants who filled up a questionnaire were given a present at the Aventis Pharma's stand at the Conference. They were asked about the perception of resistance rates of Streptococcus pneumoniae towards penicillins and macrolides in Spain and whether they agreed on using macrolides and quinolones in cases of suspected high penicillin-resistant pneumococcal infections. 843 family doctors filled up the questionnaire and 35 inquiries were dropped out because of illegibility or non responses. Out of 750 doctors who answered the question about the pneumococcal resistance towards penicillins, 312 stated to be greater than 30% (41.6) and only 90 thought to be less than 15% (12%). However, 153 doctors stated that pneumococcal resistance to macrolides was greater than 30% (23%) and 28 greater than 45% (4.2%). Respondents prefer the use of penicillins in patients with community-acquired pneumonia (344, 42.6%) but were reluctant to prescribe them in case of pneumonias suspected to be caused by resistant pneumococci (82, 10.3%). In these cases family doctors prefer the use of macrolides (251, 31.5%) and quinolones (321, 40.3%). Family doctors are aware of high resistance patterns but they think that higher pneumococcal resistance rates are reported towards penicillins than to macrolides; however, 30% of the Spanish pneumococcal strains isolated are currently resistant to macrolides and only 5% are highly resistant to penicillins. They also think that penicillin still is the first antibiotic choice in pneumococcal infections unless a resistant pneumococcus is suspected. Surprisingly, in suspected penicillin-resistant pneumococcal pneumonias too many doctors recommend the prescribing of macrolides instead of quinolones.

Incidence of imipenem hypersensitivity reactions in febrile neutropenic bone marrow transplant patients with a history of penicillin allergy.

The purpose of this retrospective study was to assess cross-hypersensitivity between imipenem/cilastatin and penicillin in patients with reported penicillin allergies. Medical records of febrile neutropenic, penicillin-allergic bone marrow transplant recipients who received imipenem/cilastatin treatment were retrospectively reviewed. The findings of this study indicate the incidence of cross-reactivity between imipenem/cilastatin and penicillin among patients with a history of penicillin allergy may be lower than previously reported.