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JAMA Jan 2019β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of... (Review)
Review
IMPORTANCE
β-Lactam antibiotics are among the safest and most effective antibiotics. Many patients report allergies to these drugs that limit their use, resulting in the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance and adverse events.
OBSERVATIONS
Approximately 10% of the US population has reported allergies to the β-lactam agent penicillin, with higher rates reported by older and hospitalized patients. Although many patients report that they are allergic to penicillin, clinically significant IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity is uncommon (<5%). Currently, the rate of IgE-mediated penicillin allergies is decreasing, potentially due to a decreased use of parenteral penicillins, and because severe anaphylactic reactions to oral amoxicillin are rare. IgE-mediated penicillin allergy wanes over time, with 80% of patients becoming tolerant after a decade. Cross-reactivity between penicillin and cephalosporin drugs occurs in about 2% of cases, less than the 8% reported previously. Some patients have a medical history that suggests they are at a low risk for developing an allergic reaction to penicillin. Low-risk histories include patients having isolated nonallergic symptoms, such as gastrointestinal symptoms, or patients solely with a family history of a penicillin allergy, symptoms of pruritus without rash, or remote (>10 years) unknown reactions without features suggestive of an IgE-mediated reaction. A moderate-risk history includes urticaria or other pruritic rashes and reactions with features of IgE-mediated reactions. A high-risk history includes patients who have had anaphylaxis, positive penicillin skin testing, recurrent penicillin reactions, or hypersensitivities to multiple β-lactam antibiotics. The goals of antimicrobial stewardship are undermined when reported allergy to penicillin leads to the use of broad-spectrum antibiotics that increase the risk for antimicrobial resistance, including increased risk of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Broad-spectrum antimicrobial agents also increase the risk of developing Clostridium difficile (also known as Clostridioides difficile) infection. Direct amoxicillin challenge is appropriate for patients with low-risk allergy histories. Moderate-risk patients can be evaluated with penicillin skin testing, which carries a negative predictive value that exceeds 95% and approaches 100% when combined with amoxicillin challenge. Clinicians performing penicillin allergy evaluation need to identify what methods are supported by their available resources.
CONCLUSIONS AND RELEVANCE
Many patients report they are allergic to penicillin but few have clinically significant reactions. Evaluation of penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship.
Topics: Amoxicillin; Anti-Bacterial Agents; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Immunoglobulin E; Immunologic Tests; Patient Acuity; Penicillins; Pregnancy; beta-Lactams
PubMed: 30644987
DOI: 10.1001/jama.2018.19283 -
JAMA Nov 2014The incidence of syphilis in the United States is increasing; it is estimated that more than 55,000 new infections will occur in 2014. Treatment regimens are... (Review)
Review
IMPORTANCE
The incidence of syphilis in the United States is increasing; it is estimated that more than 55,000 new infections will occur in 2014. Treatment regimens are controversial, especially in specific populations, and assessing treatment response based on serology remains a challenge.
OBJECTIVE
To review evidence regarding penicillin and nonpenicillin regimens, implications of the "serofast state," and treatment of specific populations including those with neurosyphilis or human immunodeficiency virus (HIV) infection and pregnant women.
EVIDENCE REVIEW
We searched MEDLINE for English-language human treatment studies dating from January 1965 until July 2014. The American Heart Association classification system was used to rate quality of evidence.
FINDINGS
We included 102 articles in our review, consisting of randomized trials, meta-analyses, and cohort studies. Case reports and small series were excluded unless they were the only studies providing evidence for a specific treatment strategy. We included 11 randomized trials. Evidence regarding penicillin and nonpenicillin regimens was reviewed from studies involving 11,102 patients. Data on the treatment of early syphilis support the use of a single intramuscular injection of 2.4 million U of benzathine penicillin G, with studies reporting 90% to 100% treatment success rates. The value of multiple-dose treatment of early syphilis is uncertain, especially in HIV-infected individuals. Less evidence is available regarding therapy for late and late latent syphilis. Following treatment, nontreponemal serologic titers should decline in a stable pattern, but a significant proportion of patients may remain seropositive (the "serofast state"). Serologic response to treatment should be evident by 6 months in early syphilis but is generally slower (12-24 months) for latent syphilis. Evidence defining treatment for HIV-infected persons and for pregnant women is limited, but available data support penicillin as first-line therapy.
CONCLUSIONS AND RELEVANCE
The mainstay of syphilis treatment is parenteral penicillin G despite the relatively modest clinical trial data that support its use.
Topics: Adult; Anti-Bacterial Agents; Female; Humans; Injections, Intramuscular; Male; Penicillin G Benzathine; Pregnancy; Syphilis
PubMed: 25387188
DOI: 10.1001/jama.2014.13259 -
Acta Otorrinolaringologica Espanola 2015Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among... (Review)
Review
Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A β-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy.
Topics: Acute Disease; Adult; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Humans; Inappropriate Prescribing; Macrolides; Penicillins; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes
PubMed: 25772389
DOI: 10.1016/j.otorri.2015.01.001 -
The Cochrane Database of Systematic... Mar 2021Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020.
OBJECTIVES
To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis.
SEARCH METHODS
We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020.
SELECTION CRITERIA
Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.
MAIN RESULTS
We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence). Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better in preventing serious but rare complications. AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amoxicillin; Ampicillin; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Child; Child, Preschool; Clindamycin; Humans; Infant; Macrolides; Middle Aged; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Streptococcal Infections; Streptococcus pyogenes; Sulfonamides; Young Adult
PubMed: 33728634
DOI: 10.1002/14651858.CD004406.pub5 -
The Journal of Allergy and Clinical... May 2021Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic...
BACKGROUND
Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic fibrosis.
OBJECTIVE
Detailed clinical characterization of a patient cohort referred with suspected piperacillin-tazobactam hypersensitivity.
METHODS
Retrospective analysis of the demographic characteristics, clinical presentation, investigation, and management of 87 patients presenting to 5 European allergy centers. Patients underwent skin prick and intradermal testing with piperacillin/tazobactam, major (penicilloyl-polylysine) and minor (sodium penilloate) determinants, amoxicillin, benzylpenicillin, flucloxacillin, co-amoxiclav, clavulanic acid, and meropenem with immediate and, where appropriate, delayed reading of tests. Skin test-negative patients underwent drug provocation to piperacillin/tazobactam and/or other penicillins. A multistep protocol was used, depending on risk assessment.
RESULTS
Forty-eight of 87 (55%) patients were diagnosed with hypersensitivity to piperacillin/tazobactam with either positive skin or drug provocation test results, of whom 10 (21%) had a diagnosis of cystic fibrosis. Twenty-six (54%) patients presented with immediate and 22 (45%) with nonimmediate hypersensitivity. Patients with cystic fibrosis predominantly presented with nonimmediate hypersensitivity (70%). Reactions were severe in 52% of immediate reactors (Brown's anaphylaxis grade 3) and moderately severe (systemic involvement) in 75% of nonimmediate reactors. The number of patients with negative skin test results tolerating reintroduction was comparable in immediate (80%) and nonimmediate (88%) hypersensitivity. One-third of patients were cross-sensitized to other penicillins. The cross-sensitization pattern raised the possibility of tazobactam allergy in 3 patients. In 21 patients selectively sensitized to piperacillin/tazobactam (12 immediate, 9 nonimmediate), tolerance to other beta-lactams was demonstrated by drug provocation testing.
CONCLUSIONS
Piperacillin-tazobactam caused immediate and nonimmediate hypersensitivity with similar frequency. Most patients were selectively sensitized and tolerated other penicillins. Some patients may be allergic to the beta-lactamase inhibitor only.
Topics: Amoxicillin; Anti-Bacterial Agents; Drug Hypersensitivity; Humans; Hypersensitivity, Immediate; Penicillins; Retrospective Studies; Skin Tests
PubMed: 33444815
DOI: 10.1016/j.jaip.2020.12.051 -
Harefuah Oct 2022Syphilis is also known as 'the great imitator' for its ability to mimic many diseases due to its extensive range of clinical manifestations. This review aims to provide... (Review)
Review
Syphilis is also known as 'the great imitator' for its ability to mimic many diseases due to its extensive range of clinical manifestations. This review aims to provide an update on the clinical presentation, diagnosis and treatment of ocular syphilis. It manifests in a spectrum of ways that can occur at any stage of the disease, and may be the only presenting feature of systemic syphilis, with the most common finding being panuveitis. The diagnosis is usually aided by serology testing: nonspecific treponemal antibodies (for screening and follow-up) and specific treponemal antibodies for confirmation of the diagnosis. The treatment for ocular syphilis is similar to neurosyphilis and includes intravenous aqueous crystalline penicillin.
Topics: Humans; Syphilis; Eye Infections, Bacterial; Penicillin G
PubMed: 36315214
DOI: No ID Found -
The American Journal of Medicine Apr 2018
Topics: Humans; Penicillin G; Penicillins; Staphylococcal Infections; Staphylococcus aureus
PubMed: 29555040
DOI: 10.1016/j.amjmed.2017.12.003 -
The Lancet. Infectious Diseases Oct 2021Intravenous benzylpenicillin is the gold-standard treatment for neurosyphilis, but it requires prolonged hospitalisation. Ceftriaxone is a possible alternative...
BACKGROUND
Intravenous benzylpenicillin is the gold-standard treatment for neurosyphilis, but it requires prolonged hospitalisation. Ceftriaxone is a possible alternative treatment, the effectiveness of which remains unclear. We aimed to assess the effectiveness of ceftriaxone compared with benzylpenicillin in the treatment of neurosyphilis.
METHODS
We did a retrospective multicentre study including patients with neurosyphilis who were treated at one of eight tertiary care centres in France, from Jan 1, 1997, to Dec 31, 2017. We defined neurosyphilis as positive treponemal and non-treponemal tests and at least one of otic syphilis, ocular syphilis, either neurological symptom with a positive result on cerebrospinal fluid (CSF)-VDRL or CSF-PCR tests, or more than five leukocytes in a CSF cell count. Patients with neurosyphilis were identified from the medical information department database of each centre and assigned to one of two groups on the basis of the initial treatment received (ie, benzylpenicillin group or ceftriaxone group). The primary outcome was the overall clinical response (ie, proportion of patients with a complete or partial response) 1 month after treatment initiation. The secondary endpoints were proportions of patients with a complete response at 1 month and serological response at 6 months, and length of hospital stay.
FINDINGS
Of 365 patients with a coded diagnosis of neurosyphilis in one of the eight care centres during 1997-2017, 208 were included in this study (42 in the ceftriaxone group and 166 in the benzylpenicillin group). The mean age of patients was 44·4 years (SD 13·4), and 193 (93%) were men. We observed 41 instances of overall clinical response (98%) in the ceftriaxone group versus 125 (76%) in the benzylpenicillin group (crude odds ratio [OR] 13·02 [95% CI 1·73-97·66], p=0·017). After propensity score weighting, overall clinical response rates remained different between the groups (OR 1·22 [95% CI 1·12-1·33], p<0·0001). 22 (52%) patients in the ceftriaxone group and 55 (33%) in the benzylpenicillin group had a complete response (crude OR 2·26 [95% CI 1·12-4·41], p=0·031), with no significant difference after propensity score weighting (OR 1·08 [95% CI 0·94-1·24], p=0·269). Serological response at 6 months did not differ between the groups (21 [88%] of 24 in the ceftriaxone group vs 76 [82%] of 93 in the benzylpenicillin group; crude OR 1·56 [95% CI 0·42-5·86], p=0·50), whereas hospital stay was shorter for patients in the ceftriaxone group than for those in the benzylpenicillin group (mean 13·8 days [95% CI 12·8-14·8] vs 8·9 days [5·7-12·0], p<0·0001). No major adverse effects were reported in either group.
INTERPRETATION
Our results suggest that ceftriaxone is similarly effective to benzylpenicillin for the treatment of neurosyphilis, potentially decreasing the length of hospital stay. Randomised, controlled trials should be done to confirm these results.
FUNDING
None.
Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Female; France; Humans; Male; Middle Aged; Neurosyphilis; Penicillin G; Retrospective Studies; Treatment Outcome
PubMed: 34051142
DOI: 10.1016/S1473-3099(20)30857-4 -
Paediatric Respiratory Reviews Sep 2022Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Actinomycosis develops when there is disruption of the mucosal barrier, and... (Review)
Review
Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Actinomycosis develops when there is disruption of the mucosal barrier, and invasion and systemic spread of the organism, which can lead to endogenous infection affecting numerous organs. It is known to spread in tissue through fascial planes and most often involves the cervicofacial (55%), abdominopelvic (20%) and thoracic (15%) soft tissue. Pulmonary actinomycosis is rare in patients under the age of five years, with the median reported age in the fifth decade. Clinical findings include chest wall mass (49%), cough (40%), pain (back, chest, shoulders) (36%), weight loss (19%), fever (19%), Draining sinuses (15%) and hemoptysis (9%). Chest x-ray findings in pulmonary actinomycosis are mostly nonspecific and can overlap with pulmonary tuberculosis, foreign body aspiration and malignancy. Endobronchial tissue aggregates may show sulphur granules, with yellow to white conglomerate areas of gram positive Actinomyces. Removal or biopsy of these large endobronchial masses must be done with care, because of the risk of bleeding and large airway obstruction. The cytology on bronchoalveolar lavage fluid may show Periodic acid-Schiff (PAS) positive stain, ZN negative and Gram-positive filamentous bacilli which is morphologically suggestive of Actinomycosis. Actinomyces spp is highly susceptible to beta lactam antibiotics, penicillin G, and amoxicillin. A minimum of 3-6 months is needed but up to 20 months of treatment may be needed. Early diagnosis and correct treatment can lead to a good prognosis with a low mortality.
Topics: Humans; Child; Child, Preschool; Periodic Acid; Actinomycosis; Actinomyces; Lung Diseases; Penicillin G; Amoxicillin; Sulfur
PubMed: 34610895
DOI: 10.1016/j.prrv.2021.09.001 -
The Journal of Antibiotics Apr 2015Because some Actinobacteria, especially Streptomyces species, are β-lactam-producing bacteria, they have to have some self-resistant mechanism. The β-lactam... (Review)
Review
Because some Actinobacteria, especially Streptomyces species, are β-lactam-producing bacteria, they have to have some self-resistant mechanism. The β-lactam biosynthetic gene clusters include genes for β-lactamases and penicillin-binding proteins (PBPs), suggesting that these are involved in self-resistance. However, direct evidence for the involvement of β-lactamases does not exist at the present time. Instead, phylogenetic analysis revealed that PBPs in Streptomyces are distinct in that Streptomyces species have much more PBPs than other Actinobacteria, and that two to three pairs of similar PBPs are present in most Streptomyces species examined. Some of these PBPs bind benzylpenicillin with very low affinity and are highly similar in their amino-acid sequences. Furthermore, other low-affinity PBPs such as SCLAV_4179 in Streptomyces clavuligerus, a β-lactam-producing Actinobacterium, may strengthen further the self-resistance against β-lactams. This review discusses the role of PBPs in resistance to benzylpenicillin in Streptomyces belonging to Actinobacteria.
Topics: Actinobacteria; Amino Acid Sequence; Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Multigene Family; Penicillin G; Penicillin-Binding Proteins; Phylogeny; Streptomyces; beta-Lactamases; beta-Lactams
PubMed: 25351947
DOI: 10.1038/ja.2014.148