Penetration of trimethoprim and sulfamethoxazole into skin blister fluid

In 32 patients the concentrations of sulfamethoxazole and trimethoprim in whole blood, plasma and skin blister fluid were studied in the course of treatment with co-trimoxazole and trimethoprim alone. Measurements were taken on the fourth day of treatment, 3 h after administration of the morning dose of the drug. The blood contained a lower concentration of sulfamethoxazole than plasma. About 70% of the sulfonamide penetrated into the exudate from plasma. Trimethoprim administered conjointly with sulfamethoxazole to a higher degree penetrated skin blister fluid to a greater extent than when given alone.     

Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Revisiting the meaning of 'sulfa' allergy.

Celecoxib, a selective cyclo-oxygenase-2 inhibitor, is a diaryl-substituted pyrazole derivative containing a sulfonamide substituent. Because of this structural component, celecoxib is contraindicated for use in patients who have demonstrated allergic reactions to sulfonamides. However, there is a lack of data demonstrating cross-reactivity among sulfonamide medications. A sulfonamide is any compound with an SO2NH2 moiety. The major difference between sulfonamide antimicrobials and other sulfonamide-containing medications such as furosemide, thiazide diuretics and celecoxib, is that sulfonamide antimicrobials contain an aromatic amine group at the N4 position. This allows for division of the sulfonamides into 2 groups: aromatic amines (i.e., sulfonamide antimicrobials) and nonaromatic amines. In addition, sulfonamide antimicrobials contain a substituted ring at the N1-position; this group is not found with nonaromatic amine-containing sulfonamides. Adverse reactions to sulfonamide antimicrobials include type I, or immunoglobulin (Ig) E-mediated reactions, hypersensitivity syndrome reactions, and severe skin reactions such as toxic epidermal necrolysis. The aromatic amine portion of the sulfonamide antimicrobial is considered to be critical in the development of latter 2 reactions. In susceptible individuals, the hydroxylamine metabolite is unable to be detoxified leading to a cascade of cytotoxic and immunological events that eventually results in the adverse reaction. Since celecoxib does not contain the aromatic amine, adverse reactions such as hypersensitivity syndrome reactions and toxic epidermal necrolysis would not be expected to occur at the same frequency as they do with sulfonamide antimicrobials. Similarly, for IgE-mediated reactions, the N1-substituent and not the sulphonamide moiety is important in determining specificity to antibodies. Celecoxib and other nonaromatic amine-containing sulfonamide medications do not contain the N1-substituent. Cross-reactivity among the various sulfonamide-containing medications has also not been substantiated by published case reports. In fact, conflicting information exists in the literature. Reports showing lack of cross-reactivity balance the few case reports suggesting cross-reactivity. Cross-reactivity between sulfonamide medications should be based on scientific data, including chemistry, metabolism, immune responses and clinical data. Based on the current information, there is no documentation for cross-reactivity between sulfonamide antimicrobials and other sulfonamide medications, such as celecoxib.     

Comparison of Two Otitis Media Models for the Study of Middle Ear Antimicrobial Pharmacokinetics

We compared two models of acute otitis media that estimate middle ear antimicrobial pharmacokinetics. Using a crossover study design, we compared a systemic drug administration model with a diffusion model we devised that measures the disappearance of antimicrobials from the middle ear. We induced acute otitis media in 14 chinchillas by inoculating S. pneumoniae into the middle ear, then administered 3 antimicrobials: amoxicillin, trimethoprim, and sulfamethoxazole. Next we collected middle ear fluid samples to analyze drug concentrations and compare rate constants for the systemic and diffusion models by analysis of variance. We found that amoxicillin K values were not affected by model testing sequence (p = 0.827) or model type (systemic versus diffusion, p = 0.310), nor were sulfamethoxazole K values: model testing sequence (p = 0.917), model type (p = 0.963). Trimethoprim K values were also not affected by model testing sequence (p = 0/760), but were by model type (p = 0.0001). Trimethoprim elimination from the diffusion model was faster (K = 0.33 ± 0.17 versus 0.57 ± 0.09 hr^–1) than from the systemic model, although it appears this was caused by sampling before drug distribution into the middle ear was complete. In conclusion, it appears K values derived from either systemic antimicrobial administration or direct middle ear instillation are similar for assessing middle ear anitmicrobial pharmacokinetics, and these models can be used interchangeably to study factors affecting otitis media treatment response.     

Anaphylaxis to lidocaine with tolerance to articaine in a 12 year old girl

True allergic reactions to local anesthetics are extremely rare and constitute less than 1% of all reactions. In addition, many of those allergic reactions are caused by the preservative constituents of the local anesthetics. Here we report a 12 year old girl with anaphylaxis to lidocaine (an amide local anesthetic) on two occasions. The allergy was confirmed by positive skin prick test to the drug. Skin testing and challenge to another amide local anesthetic (articaine) were negative. Subsequently, its use was well tolerated in a dental procedure. Up to our knowledge, this is the first report of a patient who is allergic to lidocaine and tolerant to articaine.Abbreviations: LA, local anesthetic; SPT, skin prick test; SQ, subcutaneous     

Effect of Streptococcus pneumoniae and Influenza A Virus on Middle Ear Antimicrobial Pharmacokinetics in Experimental Otitis Media

Antimicrobial treatment failures in children with acute otitis media and concomitant viral respiratory tract infection prompted us to study the effects of influenza A virus infection on middle ear antimicrobial drug penetration. Using a chinchilla model of Streptococcus pneumoniae we compared middle ear elimination rates in 4 groups of chinchillas: (1) control, (2) influenza A virus inoculation alone intranasally, (3) both influenza A and S. pneumoniae inoculation directly into the middle ear, and (4) S. pneumoniae inoculation alone into the middle ear. After infection was established, a solution containing amoxicillin, sulfamethoxazole, and trimethoprim was instilled into the middle ear and removed 4 hours later. The rate constant of elimination and half-life were calculated from measured drug concentrations initially and at 4 hours. S. pneumoniae infection alone significantly shortened the middle ear elimination half-life compared with the control group: amoxicillin, 2.65 ± 0.73 vs. 6.63 ± 2.55 hr; sulfamethoxazole, 1.75 ± 0.28 vs. 2.74 ± 0.6 hr; and trimethoprim, 1.06 ± 0.14 vs. 1.56 ± 0.34 hr (n = 16 ears, p values all <0.01). The combined influenza virus and S. pneumoniae infection significantly lengthened the half-life compared with the S. pneumoniae infection alone: amoxicillin, 5.65 ± 6.44 vs. 2.65 ± 0.73 hr; sulfamethoxazole, 2.5 ± 0.85 vs. 1.75 ± 0.28 hr; and trimethoprim, 1.26 ± 0.42 vs. 1.06 ± 0.14 hr (n = 16 ears, p values all <0.01). Influenza virus produced the longest half-lives for all 3 antimicrobials: amoxicillin 25.52 ± 14.96 hr; sulfamethoxazole, 5.46 ± 0.87 hr; and trimethoprim, 2.57 ± 0.75 hr. These effects demonstrate that influenza and S. pneumoniae infections alone and together affect middle ear antimicrobial penetration. The decreased penetration of antimicrobials that occurred with the combined viral and bacterial infection vs. the bacteria alone supports the clinical observation that patients with infections caused by both organisms may have decreased middle ear antimicrobial concentrations, producing treatment failures.     

Identification of sulfonamide-like adverse drug reactions to celecoxib in the World Health Organization database

BACKGROUND: The selective COX-2 inhibitor celecoxib has a sulfonamide structure and is contraindicated for patients with known sulfa allergy. However, there is currently no standard available for the identification of sulfonamide-related adverse drug reactions (ADRs) and the occurrence of such ADRs with celecoxib has not been established. THE AIMS OF THIS STUDY WERE: (1) to identify the typical pattern of sulfonamide ADRs from literature and verify this pattern in the World Health Organization (WHO) ADR database; and (2) to examine whether these sulfonamide ADRs occur more frequently with celecoxib than with the non-sulfonamide, COX-2 inhibitor rofecoxib. METHODS: A sulfonamide ADR pattern was derived from the most extensive textbook source of ADRs and applied to the WHO database for the three groups of sulfonamide drugs: short- and intermediate-acting sulfonamides, and sulfasalazine. ADRs reported three or more times for each of these groups were included in a 'sulfonamide template' comprising 19 ADRs relating to the skin, the blood, the liver, and anaphylaxis. This template was then applied to celecoxib and rofecoxib. RESULTS: Overall, the relative reporting rate of a sulfonamide-type ADR with celecoxib was 80% higher than with rofecoxib, whether this was based on total number of reports (RR 1.8, 95% Cl 1.6-1.9) or restricted to reports that listed coxibs as the sole suspected drugs (RR 1.8, 95% Cl 1.6-1.9). There were numerically more ADRs for celecoxib than for rofecoxib in 15 of the 19 terms. Within the ADRs in the sulfonamide template, relative reporting rate of fatal reactions was 80% higher with celecoxib (RR 1.8, 95% Cl 0.9-4.0). Even though serious sulfonamide reactions are rare, their clinical impact on patient safety warrants close monitoring as more data becomes available. Physicians should be aware of possible sulfonamide allergy when prescribing celecoxib.     

Identification of Sulfonamide-like Adverse Drug Reactions to Celecoxib in the World Health Organization Database

Summary

Background: The selective COX-2 inhibitor celecoxib has a sulfonamide structure and is contraindicated for patients with known sulfa allergy. However, there is currently no standard available for the identification of sulfonamide-related adverse drug reactions (ADRs) and the occurrence of such ADRs with celecoxib has not been established.

The aims of this study were: (1) to identify the typical pattern of sulfonamide ADRs from literature and verify this pattern in the World Health Organization (WHO) ADR database; and (2) to examine whether these sulfonamide ADRs occur more frequently with celecoxib than with the non-sulfonamide, COX-2 inhibitor rofecoxib.

Methods: A sulfonamide ADR pattern was derived from the most extensive textbook source of ADRs and applied to the WHO database for the three groups of sulfonamide drugs: short- and intermediate-acting sulfonamides, and sulfasalazine. ADRs reported three or more times for each of these groups were included in a ‘sulfonamide template’ comprising 19 ADRs relating to the skin the blood the liver and anaphylaxis. This template was then applied to celecoxib and rofecoxib.

Results: Overall, the relative reporting rate of a sulfonamide-type ADR with celecoxib was 80% higher than with rofecoxib, whether this was based on total number of reports (RR 1.8, 95% CI 1.6-1.9) or restricted to reports that listed coxibs as the sole suspected drugs (RR 1.8, 95% CI 1.6-1.9). There were numerically more ADRs for celecoxib than for rofecoxib in 15 of the 19 terms. Within the ADRs in the sulfonamide template, relative reporting rate of fatal reactions was 80% higher with celecoxib (RR 1.8, 95% CI 0.9-4.0). Even though serious sulfonamide reactions are rare, their clinical impact on patient safety warrants close monitoring as more data becomes available. Physicians should be aware of possible sulfonamide allergy when prescribing celecoxib.     

Celecoxib-induced erythema multiforme with glyburide cross-reactivity

Erythema multiforme is an acute inflammatory skin reaction that often is caused by drugs, especially sulfonamides and their derivatives. Celecoxib, a cyclooxygenase-2 inhibitor, is a sulfonamide derivative commonly prescribed to treat arthritis in patients who cannot tolerate or who have a contraindication for taking traditional nonsteroidal antiinflammatory agents. A 57-year-old man with a previously undocumented sulfa allergy experienced an allergic skin reaction and had difficulty breathing secondary to throat swelling. His condition was believed to be erythema multiforme associated with the introduction of celecoxib into his drug regimen. His drug therapy was discontinued, but a subsequent reaction occurred when the sulfonamide derivative glyburide was reintroduced. It is important for clinicians to obtain a careful history and perform a thorough medical evaluation in all patients receiving sulfonamides and their derivatives, as a potentially life-threatening allergic reaction may be prevented.     

Investigation on possible allergenicity of 19 different commercial enzymes used in the food industry.

The aim of the study was to investigate the safety to allergic patients of 19 commercially available and authority-approved enzymes used in the food industry. Enzymes produced by genetically modified organisms were included. Four hundred consecutive adult patients with a diagnosed allergy to inhalation allergens, food allergens, bee or wasp were included. All had at least one positive skin prick test to the above allergens. Skin prick testing with the 19 enzymes was performed on the forearm and if positive (in 13 patients), in vitro histamine release from blood basophils were performed. Patients with positive results in skin prick test were subsequently reinvestigated with further purified enzymes and finally challenged orally with the enzymes in a double-blind, placebo-controlled protocol. Only one reaction to a placebo challenge was seen. In some instances a positive skin prick test result or a positive histamine release was seen elicited by the enzymes, but since none of the patients were positive to any of the commercial enzymes in the subsequent oral challenges using exaggerated dosages of the enzymes compared to normal daily intake, the findings are without clinical relevance. A wide variety of enzyme classes and origins was included in the study. Because there were no allergenic findings of clinical relevance it is concluded that ingestion of food enzymes in general is not considered to be a concern with regard to food allergy.     

Pharmacist-managed service providing penicillin allergy skin tests.

PURPOSE: A penicillin allergy skin-testing service run by pharmacists is described. SUMMARY: A board-certified allergist trained pharmacists at a tertiary care teaching hospital to administer penicillin allergy skin tests and interpret the results. A major objective of the service was to avoid unnecessary use of vancomycin and quinolones in patients claiming but not actually having a penicillin allergy. Patients with a severe type I reaction to penicillin during the preceding five years, patients with a confirmed history of a type II-IV reaction to penicillin, and severely immunosuppressed patients were not eligible for testing. As of July 2003, 26 patients had been enrolled in the service. A type I penicillin reaction was ruled out by the drug allergy history for 3 patients. The results were negative in 22 of the 23 patients who received skin testing, and in 1 the result was indeterminate. A penicillin or a beta-lactam antibiotic was administered to all 26 patients. No patient had a significant adverse reaction to skin testing or drug administration. CONCLUSION: A pharmacist-managed penicillin allergy skin-testing service was well received by physicians and showed potential to avoid unnecessary use of alternative antibiotics.     

Susceptibility patterns of Streptococcus pneumoniae isolates in North America (2002-2003): contemporary in vitro activities of amoxicillin/clavulanate and 15 other antimicrobial agents

A contemporary (2002-2003) national collection of 2100 strains of Streptococcus pneumoniae obtained from 30 sites in the nine United States (US) census regions were tested to determine the comparative antimicrobial properties of amoxicillin/clavulanate and 15 other antimicrobials. The rank order of antimicrobials with the lowest susceptibility rates was: penicillin (67.9%)or=41.1%), trimethoprim/sulphamethoxazole (38.9%), tetracyclines (22.2%) and clindamycin (10.0%). Geographical variation in the susceptibility patterns among US census zones was present with lowest penicillin and erythromycin susceptibility noted for West South Central and West North Central zones (or=+0.9%), sinus isolates (+2.7%), middle ear fluid isolates (+5.5%), penicillin-resistant strains (>or=+5.8%) and strains from patients <2 years of age (>or=+2.4%). Local and global surveillance studies of common respiratory pathogens such as S. pneumoniae remain instrumental to guide clinicians in appropriate empirical treatments and to emphasize the need for prudent antimicrobial use.     

Friday asthma crisis in the daughter of two bakers

The prevalence of sesame food allergy continues to increase worldwide. The diagnostic tools to confirm such allergy include skin prick tests, specific IgEs and food challenge. We report the case of a 7-year-old girl who presented recurrent episodes of wheezing and dyspnoea. After performing skin tests and evaluating specific IgEs we hypothesised an allergy to sesame. Our patient actually benefitted from avoiding any contact with sesame and sesame seeds. We confirmed our diagnosis through an inhalation food challenge. Further, by reviewing her personal history, we suspect inhalation was the mechanism in which the girl became sensitised to sesame.     

Adverse reactions to β-lactam antimicrobials

INTRODUCTION: Beta-lactam antibiotics are among the most clinically useful antimicrobials used in medicine. Unfortunately, adverse events related to their use remain poorly understood by many clinicians and, in particular, the misdiagnosis of β-lactam allergy and misunderstanding of crossreactivity among members of the β-lactam antibiotics may effectively eliminate a whole class of antimicrobials from use and require the use of broader spectrum agents with less well-established safety profiles. AREAS COVERED: This review describes the range, diagnosis and management of adverse events associated with β-lactam antimicrobials, particularly focusing on recognition, diagnosis and management of true allergy and risk of cross-sensitivity between β-lactam antibiotics. A literature review was undertaken using PubMed, focusing primarily on literature published in the past 10 years relating to β-lactam adverse events and allergy. EXPERT OPINION: Beta-lactams are generally safe drugs and serious adverse events are rare and allergy is overdiagnosed. Accurate diagnosis can usually be achieved through careful history and in some instances skin or in vitro testing is required. Even among individuals with true immediate-type allergy to penicillin, most cephalosporins are readily tolerated and desensitization is usually an option in cases where no alternate antimicrobials are available. Other allergic reactions (Type II, III and IV) are rare and avoidance of the culprit agent is generally recommended. Nonallergic or morbilliform rashes are generally not allergic in nature and should not prompt drug or class avoidance. Other adverse events are frequently dose-related and can be avoided by appropriate dosing and consideration of renal function.     

Antimicrobial susceptibility of Escherichia coli from community-acquired urinary tract infections in Europe: the ECO·SENS study revisited

This study determined the antimicrobial susceptibility of Escherichia coli causing community-acquired, acute, uncomplicated, non-recurrent urinary tract infection in unselected women aged 18-65 years and compared the results with those obtained 8 years earlier in the first ECO·SENS study (1999-2000). During 2007-2008, urine samples were taken from 1697 women in Austria, Greece, Portugal, Sweden and the UK. The countries were chosen to represent areas of Europe indicated to have more (Greece and Portugal) or less (UK, Austria and Sweden) problems with resistance. Antimicrobial susceptibility testing of 903 E. coli isolates (150-200 isolates per country) to 14 antimicrobials was performed by disk diffusion using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. In E. coli, resistance to mecillinam, cefadroxil (representing oral cephalosporins), nitrofurantoin, fosfomycin trometamol, gentamicin and the third-generation cephalosporins cefotaxime and ceftazidime was <2%, with the following exceptions: gentamicin in Portugal (2.8%); fosfomycin in Greece (2.9%); and cephalosporins in Austria (2.7-4.1%). Resistance levels were higher for amoxicillin/clavulanic acid (2.0-8.9%) and ciprofloxacin (0.5-7.6%) and much higher to ampicillin (21.2-34.0%), sulfamethoxazole (21.2-31.3%), trimethoprim (14.9-19.1%) and trimethoprim/sulfamethoxazole (14.4-18.2%). Resistance to quinolones and trimethoprim increased between the ECO·SENS I (1999-2000) and ECO·SENS II (2007-2008): nalidixic acid 4.3% to 10.2%; ciprofloxacin 1.1% to 3.9%; and trimethoprim 13.3% to 16.7%. In the previous study, no isolates with extended-spectrum β-lactamase were found; however, in the present study 11 isolates were identified as having either CTX-M or AmpC.     

Knowledge and attitudes of American pharmacists concerning sulfonamide allergy cross-reactivity

Objective Pharmacists are commonly confronted with patients with a history of sulfonamide allergy. Basic immunologic and clinical data suggest a low likelihood of a patient with a history of sulfonamide hypersensitivity developing an allergic reaction to a non-antimicrobial sulfonamide drug. We conducted a survey to describe the knowledge and attitudes of licensed pharmacists concerning sulfonamide allergy cross-reactivity. Methods A survey instrument was developed and sent to all licensed pharmacists in the state of Iowa. The survey recorded demographic information and included six patient scenarios designed to elicit responses concerning sulfonamide allergy cross-reactivity with a number of non-antimicrobial sulfonamides. Results A total of 421 surveys were returned for a 39% response rate. There was a wide discrepancy in approaches to patients with a history of sulfonamide allergy prescribed a sulfonamide containing non-antibiotic. Differences depended on previous history of tolerating the medication in question, the degree of cautionary statements in product literature, and the familiarity the pharmacist had with the product. Conclusion Our survey suggests a significant diversity in knowledge and attitudes of pharmacists concerning cross-reactivity of sulfonamide antimicrobials and other drugs with a sulfonamide moiety. Depth of training in this area may be an associative factor.     

Delayed allergy to aminopenicillins: clinical and immunological findings

Aminopenicillins are the most used beta-lactam antibiotics. Morbilliform or maculopapular rashes are rather frequent during therapy with aminopenicillins. The pathogenesis of these reactions is often due to a cell-mediated allergy. The aim of this work is to characterize patients with cell-mediated allergy to aminopenicillins and to identify alternative beta-lactam drugs that can be safely administered to these patients. We studied 27 subjects affected by cell-mediated allergy to aminopenicillins. The diagnosis was made on the basis of positivity of patch tests with aminopenicillins. These patients then underwent an allergological evaluation (skin and patch tests, oral and/or intramuscular challenge tests) with a wide spectrum of beta-lactam antibiotics. Our work highlights the following main characteristics of cell-mediated allergy to aminopenicillins: time elapsing between drug administration and onset of symptoms of about 2 days; the maculopapular rash and delayed appearance of urticaria/angioedema were the most typical symptoms (82.8 percent of cases); a cross-reactivity with aminocephalosporins is usually absent, or it is limited to cephalexin (in our study, in fact, just 3 out of 20 patients challenged with cephalexin showed a positive oral challenge test); all the beta-lactams, other than aminopenicillins, are well tolerated. Patch tests represent a specific diagnostic tool with a good predictive value of identifying alternative drugs that can be safely administered to patients with beta-lactam allergy. Our patients could tolerate other beta-lactam drugs after a complete allergological evaluation. On the basis of our study, cell-mediated allergy to aminopenicillins should be considered a well-defined nosologic entity.     

Effects of drugs on aminophylline elimination in rats

Effects of phenobarbital, phenytoin, carbamazepine, cimetidine, erythromycin, combination of sulfamethoxazole + trimethoprim (5:1), and rifampicin (rifampin) on the elimination of aminophylline were examined in female rats. Aminophylline was administered i.p. in a dose of 13.33 mg/kg. Blood samples were collected 0.5, 2, 4 and 7 h after the administration of the injection; one measurement was performed from one blood sample. Plasma aminophylline levels were measured by a modified HPLC method. The elimination half-life of the untreated control group (n = 27) was 4.62 h. The pretreatments with drugs examined were carried out by a gastric tube. The half-life of aminophylline after phenobarbital (10 mg/kg, 7 days, n = 29) was 2.09 h; after phenytoin (10 mg/kg, 7 days, n = 29), 2.47 h; after carbamazepine (400 mg/d, 7 days, n = 25), 2.19 h; after cimetidine (in cimetidine-treated group the blood samples were collected 0.5, 4 and 7 h after the aminophylline injection) (40 mg/kg, 7 days, n = 13), 1.77 h; after erythromycin (800 mg/d, 7 days, n = 28), 2.51 h; after the combination of sulfamethoxazole + trimethoprim in ratio of 5:1 (50 mg/kg, 7 days, n = 23), 2.85 h; and after rifampicin (300 mg/kg, 21 days, n = 23), 2.74 h. Sulfamethoxazole presumably interfered with the HPLC examination of aminophylline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antimicrobial Activity of Tebipenem and Comparators against Enterobacterales from diverse Outpatient Centers and Nursing Homes in the United States

IntroductionTebipenem is a potential option for the treatment of a range of infections because of its oral dosing coupled with the safety profile of the β-lactam antimicrobial class.ObjectivesTo evaluate tebipenem in vitro activity against a challenge set of clinical Enterobacterales collected from outpatient and community settings.Methods618 Enterobacterales isolates were submitted by 11 geographically dispersed U.S medical centers that processed cultures from affiliated outpatient centers in 2022. Susceptibility tests for tebipenem and comparator agents were performed by broth microdilution. Extended-spectrum-β-lactamase (ESBL)-like isolates were identified phenotypically. Multidrug-resistant isolates were non-susceptible to ≥1 agent in ≥3 antimicrobial classes. Genotypic testing (CarbaR) was conducted on select isolates.ResultsIsolates (59% Escherichia coli) were recovered from patients seen predominantly in urology/nephrology (24%), nursing home/long-term care (21%), and ambulatory/primary care (21%) clinics. Comparator agent susceptibility rates against all isolates were as follows: levofloxacin (67.5%), amoxicillin/clavulanate (73.6%), cefixime (70.4%), cefpodoxime (70%), cephalexin (61.7%), ceftriaxone (74.4%), cefazolin (63.8%), ertapenem (97.6%), meropenem (99.7%), nitrofurantoin (64.9%), and sulfamethoxazole/trimethoprim (70.9%). Overall, 90.3% (558/619) of isolates were inhibited at a tebipenem MIC of ≤0.125 mg/L (MIC_50/90, 0.016/0.125 mg/L), including 85.7% inhibition of ESBL-phenotype isolates (n=161; MIC_50/90, 0.03/0.25 mg/L), 86.3% of levofloxacin and sulfamethoxazole/trimethoprim co-resistant isolates (n=95; MIC_50/90, 0.016/0.25 mg/L) and 84.3% of multidrug-resistant isolates (n = 172; MIC_50/90, 0.03/0.25 mg/L). Carbapenemase genes were observed in 2 ESBL-phenotype isolates with a tebipenem MIC of ≥0.5 mg/L.ConclusionRelative to common oral comparators, these data demonstrate excellent tebipenem in vitro activity against Enterobacterales isolated from patients receiving care in outpatient settings, including urology clinics and nursing homes.     

磺胺类药物过敏和交叉过敏的研究进展

磺胺类药物是指含有-SO2NH2结构的药物。磺胺类药物的交叉过敏仍是困扰临床的一个用药难题。有磺胺类抗菌药过敏史的患者在临床上并不罕见,这些患者是否可以使用其他磺胺类药物,相关药品说明书的描述并不一致,也无标准的操作流程或指南。本文回顾了磺胺类抗菌药发生超敏反应的机制,发现其发生主要与磺胺类抗菌药N4位的芳香胺取代基和N1位的杂环取代基有关,而多数磺胺类非抗菌药(如呋塞米、噻嗪类利尿剂、塞来昔布等)并不含有这两个取代基,因此磺胺类抗菌药和非抗菌药之间发生交叉过敏的可能性较低。此外,本文也对磺胺类药物交叉过敏的相关临床研究进行了回顾。一个大规模的回顾性研究提示,有磺胺类抗菌药过敏史者使用磺胺类非抗菌药过敏反应的发生率较无磺胺过敏史者高,但并非与磺胺基团有关,而是和患者本身过敏反应易感性高有关。磺胺类抗菌药和非抗菌药之间发生交叉过敏的理论和循证依据尚不充分,但鉴于有磺胺类抗菌药过敏史的患者对药物过敏的易感性较高,这些患者是否可使用其他磺胺类药物,取决于相关药品说明书的规定、既往发生过敏反应的严重程度以及是否有其他替代药物。