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BMC Infectious Diseases Sep 2023Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an...
Empirical antibiotic treatment for community-acquired pneumonia and accuracy for Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae: a descriptive cross-sectional study of adult patients in the emergency department.
BACKGROUND
Many factors determine empirical antibiotic treatment of community-acquired pneumonia (CAP). We aimed to describe the empirical antibiotic treatment CAP patients with an acute hospital visit and to determine if the current treatment algorithm provided specific and sufficient coverage against Legionella pneumophila, Mycoplasma pneumoniae, and Clamydophila pneumoniae (LMC).
METHODS
A descriptive cross-sectional, multicenter study of all adults with an acute hospital visit in the Region of Southern Denmark between January 2016 and March 2018 was performed. Using medical records, we retrospectively identified the empirical antibiotic treatment and the microbiological etiology for CAP patients. CAP patients who were prescribed antibiotics within 24 h of admission and with an identified bacterial pathogen were included. The prescribed empirical antibiotic treatment and its ability to provide specific and sufficient coverage against LMC pneumonia were determined.
RESULTS
Of the 19,133 patients diagnosed with CAP, 1590 (8.3%) patients were included in this study. Piperacillin-tazobactam and Beta-lactamase sensitive penicillins were the most commonly prescribed empirical treatments, 515 (32%) and 388 (24%), respectively. Our analysis showed that 42 (37%, 95% CI: 28-47%) of 113 patients with LMC pneumonia were prescribed antibiotics with LMC coverage, and 42 (12%, 95% CI: 8-15%) of 364 patients prescribed antibiotics with LMC coverage had LMC pneumonia.
CONCLUSION
Piperacillin-tazobactam, a broad-spectrum antibiotic recommended for uncertain infectious focus, was the most frequent CAP treatment and prescribed to every third patient. In addition, the current empirical antibiotic treatment accuracy was low for LMC pneumonia. Therefore, future research should focus on faster diagnostic tools for identifying the infection focus and precise microbiological testing.
Topics: Humans; Adult; Legionella pneumophila; Mycoplasma pneumoniae; Cross-Sectional Studies; Retrospective Studies; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination; Emergency Service, Hospital; Pneumonia; Community-Acquired Infections
PubMed: 37670282
DOI: 10.1186/s12879-023-08565-6 -
Revista Alergia Mexico (Tecamachalco,... Sep 2023To confirm the presence of allergy to penicillin and amoxicillin by in vivo exposure tests in patients with a history of immediate reaction to these drugs. Methods:... (Observational Study)
Observational Study
OBJECTIVES
To confirm the presence of allergy to penicillin and amoxicillin by in vivo exposure tests in patients with a history of immediate reaction to these drugs. Methods: Observational, cross-sectional, descriptive and prolective study. Patients between 12 and 60 years old with a history of immediate reaction after administration of penicillin and/or amoxicillin were included. Skin prick and intradermal tests were performed with benzylpenicilloyl polylysine and penicillin G, as well as oral challenge with amoxicillin.
RESULTS
Ten female and 3 male patients were included. The mean age was 39 years. In 84.6% of the cases the last adverse drug reaction occurred 10 years ago and in all cases it manifested with urticaria. Allergy to penicillin was corroborated in only 38.4% of cases. The most frequent adverse reaction after in vivo exposure tests was pruritus in 23%.
CONCLUSIONS
Patients with suspected penicillin allergy should be evaluated by in vivo exposure testing with major and minor determinants to corroborate or rule out allergic reactions and improve treatment conditions.
Topics: Humans; Male; Female; Adult; Child; Adolescent; Young Adult; Middle Aged; Cross-Sectional Studies; Skin Tests; Penicillins; Amoxicillin; Drug Hypersensitivity; Urticaria; Anti-Bacterial Agents
PubMed: 37933932
DOI: 10.29262/ram.v70i3.1261 -
The Journal of Antimicrobial... Aug 2023Methicillin-resistant Staphylococcus pseudintermedius (MRSP) lineages harbouring staphylococcal cassette chromosome (SCC) mec types IV, V and ΨSCCmec57395 usually...
BACKGROUND
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) lineages harbouring staphylococcal cassette chromosome (SCC) mec types IV, V and ΨSCCmec57395 usually display low oxacillin MICs (0.5-2 mg/L).
OBJECTIVES
To evaluate how oxacillin MICs correlate with PBP mutations and susceptibility to β-lactams approved for veterinary use.
METHODS
Associations between MICs and PBP mutations were investigated by broth microdilution, time-kill and genome sequence analyses in 117 canine MRSP strains harbouring these SCCmec types. Clinical outcome was retrospectively evaluated in 11 MRSP-infected dogs treated with β-lactams.
RESULTS
Low-level MRSP was defined by an oxacillin MIC <4 mg/L. Regardless of strain genotype, all low-level MRSP isolates (n = 89) were cefalexin susceptible, whereas no strains were amoxicillin/clavulanate susceptible according to clinical breakpoints. Exposure to 2× MIC of cefalexin resulted in complete killing within 8 h. High (≥4 mg/L) oxacillin MICs were associated with substitutions in native PBP2, PBP3, PBP4 and acquired PBP2a, one of which (V390M in PBP3) was statistically significant by multivariable modelling. Eight of 11 dogs responded to systemic therapy with first-generation cephalosporins (n = 4) or amoxicillin/clavulanate (n = 4) alone or with concurrent topical treatment, including 6 of 7 dogs infected with low-level MRSP.
CONCLUSIONS
Oxacillin MIC variability in MRSP is influenced by mutations in multiple PBPs and correlates with cefalexin susceptibility. The expert rule recommending that strains with oxacillin MIC ≥0.5 mg/L are reported as resistant to all β-lactams should be reassessed based on these results, which are highly clinically relevant in light of the shortage of effective antimicrobials for systemic treatment of MRSP infections in veterinary medicine.
Topics: Dogs; Animals; Methicillin-Resistant Staphylococcus aureus; Cephalexin; Methicillin Resistance; Retrospective Studies; Dog Diseases; Staphylococcal Infections; Oxacillin; Amoxicillin-Potassium Clavulanate Combination; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37294541
DOI: 10.1093/jac/dkad182 -
The Lancet. Infectious Diseases Apr 2024Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence... (Randomized Controlled Trial)
Randomized Controlled Trial
Oral linezolid compared with benzathine penicillin G for treatment of early syphilis in adults (Trep-AB Study) in Spain: a prospective, open-label, non-inferiority, randomised controlled trial.
BACKGROUND
Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG).
METHODS
We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than -10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis.
FINDINGS
Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference -29·6, 95% CI -50·5 to -8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up.
INTERPRETATION
The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis.
FUNDING
European Research Council and Fondo de Investigaciones Sanitarias.
Topics: Adult; Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Linezolid; Macrolides; Penicillin G Benzathine; Prospective Studies; Reagins; Recurrence; Spain; Syphilis; Treatment Outcome
PubMed: 38211601
DOI: 10.1016/S1473-3099(23)00683-7 -
Gene Jan 2024The aim of this study was to obtain the Lactobacillus plantarum ATCC14917 with high-level resistance to penicillin and evaluate their probiotic traits using laboratory...
The aim of this study was to obtain the Lactobacillus plantarum ATCC14917 with high-level resistance to penicillin and evaluate their probiotic traits using laboratory evolution assay and whole-genome sequencing. In penicillin environment, the minimum inhibitory concentration (MIC) of L. plantarum to penicillin increased from 1 μg/mL to 16 μg/mL and remained stable after the removal of antibiotic pressure, suggesting that the resistance acquisition to penicillin was an irreversible process. Subsequently, change of probiotic characteristics was further evaluated, and the results showed that the acid tolerance, bile tolerance and adhesion ability were significantly declined in the highly resistant strains. Whole-genome sequencing indicated that genes encoding hypothetical protein, LPXTG-motif cell wall anchor domain protein and acetyltransferase were detected in highly resistant L. plantarum, and these genes were still present after the following subculture in the absence of penicillin, suggesting that these three mutants might be the main reason for the development of penicillin resistance. The homology-based analysis of surrounding DNA regions of mutant genes was further performed and indicated that no resistant genes were located on mobile elements in evolved L. plantarum strains, signifying that the spread of antibiotic resistance genes in the gut would not occur for these mutant genes. This study provided a basis for the combined use of highly resistant L. plantarum and penicillin in the treatment of pathogen induced gut diseases.
Topics: Lactobacillus plantarum; Anti-Bacterial Agents; Penicillins; Probiotics; Penicillin Resistance
PubMed: 37741594
DOI: 10.1016/j.gene.2023.147823 -
The American Journal of Medicine Oct 2023
Topics: Humans; Penicillin G Benzathine; Neurosyphilis
PubMed: 37734810
DOI: 10.1016/j.amjmed.2023.05.022 -
Annals of Clinical Microbiology and... Jul 2023Hybrid therapy (HT) is a non-bismuth quadruple therapy created to surpass Helicobacter pylori's (H. pylori) resistance rates to antibiotics. HT has excellent eradication... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hybrid therapy (HT) is a non-bismuth quadruple therapy created to surpass Helicobacter pylori's (H. pylori) resistance rates to antibiotics. HT has excellent eradication rates, as well as a very good compliance and safety profile. We aim to compare HT with sequential therapy (ST) and concomitant therapy (CT) for the eradication of H. pylori.
METHODS
This systematic review was conducted following the principles of the PRISMA guidelines. Literature was electronically searched on the CENTRAL library, PubMed, Embase, Scopus, LILACS, and ClinicalTrials.gov. Only randomized controlled trials were included. The primary outcome evaluated was eradication rate of H. pylori. The secondary outcomes evaluated were adverse events and compliance rates. Meta-analyses were performed with Cochrane Review Manager 5.4. The Mantel-Haenszel method was used to estimate the pooled relative risk and 95% confidence interval of the eradication rates between HT and other regimens, as well as the secondary outcomes.
RESULTS
10 studies were included, comprising 2993 patients. The mean eradication rates achieved by HT with intention-to-treat (ITT) and per-protocol (PP) analyses were, respectively, 86% (range: 79.2-90.8%) and 91.7% (range: 82.6-96.1%). No statistically significant difference was found in ITT eradication rate between HT and CT (relative risk: 1; 95% CI: 0.96- 1.03) and between HT and ST (relative risk: 1.02; 95% CI: 0.92-1.14). PP analysis revealed similar results. HT was associated with higher compliance rates than CT and slightly lower than ST. As far as adverse events are concerned, this meta-analysis demonstrated a higher occurrence of adverse events on the group of patients treated with CT when compared with HT. HT and ST showed similar results.
CONCLUSION
HT has similar eradication, compliance and adverse event rates when compared to ST, but a better safety profile than the CT.
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Drug Therapy, Combination; Anti-Bacterial Agents; Treatment Outcome; Amoxicillin
PubMed: 37403171
DOI: 10.1186/s12941-023-00582-2 -
Sexually Transmitted Diseases Dec 2023There is a paucity of Neisseria gonorrhoeae antimicrobial resistance data from resource-constrained settings because of the lack of diagnostic testing and limited scale...
BACKGROUND
There is a paucity of Neisseria gonorrhoeae antimicrobial resistance data from resource-constrained settings because of the lack of diagnostic testing and limited scale of surveillance programs. This study aimed to determine the antimicrobial resistance profile of N. gonorrhoeae in the rural Eastern Cape province of South Africa.
METHODS
Specimens for N. gonorrhoeae culture were obtained from men with urethral discharge and women with vaginal discharge attending primary health care facilities. Direct inoculation of the agar plates was performed followed by culture and drug susceptibility testing using the Etest at the laboratory. Whole-genome sequencing of the isolates was performed to identify resistance-determining variants.
RESULTS
One hundred N. gonorrhoeae isolates were obtained. Most strains were nonsusceptible to ciprofloxacin (76%), tetracycline (75%), and penicillin G (72%). The gyrA S91F mutation was present in 68 of 72 ciprofloxacin-resistant isolates (94%), with concurrent parC mutations in 47 of 68 (69%); gyrA I250M was the only mutation in 4 other resistant strains. One azithromycin-resistant isolate was identified with a minimal inhibitory concentration (MIC) of 8.0 mg/L and the 23S rDNA gene mutation C2597T. The median MIC of cefixime was 0.016 mg/L (range, 0.016-0.064 mg/L), and that of ceftriaxone was 0.016 mg/L (range, 0.016 mg/L). Whole-genome sequencing showed 58 sequence types as revealed in N. gonorrhoeae sequence typing for antimicrobial resistance and 70 sequence types in N. gonorrhoeae multiantigen sequence typing.
CONCLUSIONS
This study confirmed high rates of N. gonorrhoeae antimicrobial resistance to ciprofloxacin, penicillin G, and tetracycline in our setting. The MICs of cephalosporins are reassuring for ceftriaxone use in syndromic treatment regimens, but the identification of azithromycin resistance warrants further attention.
Topics: Male; Female; Humans; Anti-Bacterial Agents; Neisseria gonorrhoeae; Azithromycin; Ceftriaxone; Microbial Sensitivity Tests; South Africa; Drug Resistance, Bacterial; Mycobacterium tuberculosis; Gonorrhea; Ciprofloxacin; Tetracycline; Penicillin G; Molecular Typing
PubMed: 37820114
DOI: 10.1097/OLQ.0000000000001877 -
Internal Medicine (Tokyo, Japan) Aug 2023
Topics: Humans; Metronidazole; Helicobacter pylori; Japan; Anti-Bacterial Agents; Clarithromycin; Helicobacter Infections; Amoxicillin; Drug Therapy, Combination; Proton Pump Inhibitors
PubMed: 36631099
DOI: 10.2169/internalmedicine.1282-22 -
Clinical Medicine (London, England) Mar 2024The overdiagnosis of penicillin allergy and misclassification of non-truly allergic reactions is a growing public health problem, associated with the overuse of...
BACKGROUND
The overdiagnosis of penicillin allergy and misclassification of non-truly allergic reactions is a growing public health problem, associated with the overuse of broad-spectrum and restricted antimicrobials. We aimed to evaluate the impact of penicillin allergy status on antimicrobial prescribing.
METHODS
A retrospective study of inpatients with a documented penicillin allergy receiving antimicrobials was conducted from 1 April to 1 July 2021. Antimicrobial prescribing and clinical characteristics were compared between patients with an active penicillin allergy label and those whose label was removed following antimicrobial stewardship team review. Antimicrobials were classified in two categories: i) 'Access' (recommended), ii) 'Watch and Reserve' (restricted) according to WHO AWaRe classification, a tool to guide appropriate antibiotic use.
RESULTS
437 patients with a documented penicillin allergy receiving antimicrobials were included. 353 patients with an active penicillin allergy label, more frequently received antimicrobials from the 'Watch and Reserve list' (283;80% vs 30;37%; p<0.001). In contrast, 84 patients who were de-labelled received more often antimicrobials from the 'Access list' (53;63% vs 64;18%; p<0.001).
CONCLUSIONS
Penicillin allergy reviews and de-labelling strategies may reduce the use of restricted antimicrobials under the 'Watch and Reserve list'. This practice should be encouraged and reinforced in all hospitals.
Topics: Humans; Retrospective Studies; Penicillins; Male; Female; Drug Hypersensitivity; Middle Aged; Aged; Anti-Bacterial Agents; Antimicrobial Stewardship; Aged, 80 and over; Adult; Hospitalization
PubMed: 38382835
DOI: 10.1016/j.clinme.2024.100024