Objectives: To determine the nature, prevalence and description accuracy of recorded antibiotic allergy labels (AALs) in a cohort of general medical inpatients, and to assess the feasibility of an oral antibiotic re‐challenge study. Design: Multicentre cross‐sectional study. Setting and participants: All patients admitted to the general medical units of Austin Health and Alfred Health, 18 May – 5 June 2015. Main outcome measures: Baseline demographics, medical and allergy history, infection diagnoses and antibiotic prescribing data for general medical inpatients were collected. A questionnaire was administered to clarify AAL history, followed by correlation of responses with electronic and admissions record descriptions. A hypothetical oral re‐challenge in a supervised setting was offered to patients with low risk allergy phenotypes (non‐immediate reaction, non‐severe cutaneous adverse reaction, or unknown reaction more than 10 years ago). Results: Of the 453 inpatients, 107 (24%) had an AAL (median age, 82 years; interquartile range, 74–87 years); 160 individual AALs were recorded, and there was a mismatch in AAL description between recording platforms in 25% of cases. Most patients with an AAL were women (64%; P < 0.001), and more presented with concurrent immunosuppression than those without an AAL (23% v 8%; P < 0.001). β‐Lactam penicillins were employed less frequently in patients with an AAL (16% v 35%; P = 0.02), while ceftriaxone (32% v 20%; P = 0.02) and fluoroquinolones (6% v 2%; P = 0.04) were used more often. Fifty‐four per cent of patients with AALs were willing to undergo oral re‐challenge, of whom 48% had a low risk allergy phenotype. Conclusions: AAL prevalence in general medical inpatients was 24%, and was associated with excessive use of broad spectrum antibiotics. Allergies in a large proportion of patients with AALs were incorrectly documented, and were non‐immune‐mediated and potentially amenable to oral re‐challenge. A direct oral re‐challenge study in carefully selected patients with low risk allergy phenotypes appears feasible.
Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is recommended to address the variability in exposure observed in critical illness. However, the impact of TDM-guided dosing on clinical outcomes remains unknown. We conducted systematic review and meta-analysis on TDM-guided dosing and clinical outcomes (all-cause mortality, clinical cure, microbiological cure, treatment failure, hospital and ICU length of stay, target attainment, antibiotic-related adverse events, and emergence of resistance) in critically ill patients with suspected or proven sepsis. Eleven studies (n = 1463 participants) were included. TDM-guided dosing was associated with improved clinical cure (Relative Risk 1.17; 95% Confidence Interval [1.04, 1.31]), microbiological cure (1.14; [1.03, 1.27]), treatment failure (0.79; [0.66, 0.94]), and target attainment (1.85; [1.08, 3.16]). No associations with mortality and length of stay were found. TDM-guided dosing improved clinical and microbiological cure, and treatment response. Larger, prospective randomized trials are required to better assess the utility of beta-lactam TDM in critically ill patients.
Introduction. Chromobacterium violaceum is an opportunistic human pathogen, associated with significant mortality, and has been reported in patients with chronic granulomatous disease (CGD), a genetic condition causing impaired phagocytosis.Case presentation. A 28-year-old man with a history of CGD presented with fever, pharyngitis, cervical lymphadenopathy and internal jugular vein thrombosis, following travel to the rural Solomon Islands. C. violaceum was recovered from his blood. The patient recovered after treatment with meropenem and trimethoprim/sulfamethoxazole.Conclusion. To the best of our knowledge, this is the first case report of internal jugular vein thrombophlebitis (Lemierre’s syndrome) caused by C. violaceum in a patient with CGD. A review of the literature demonstrated that the diagnosis of C. violaceum preceded the diagnosis of CGD in the majority of cases. This case emphasizes the importance of this organism in patients with CGD who live in or visit tropical areas.
Objectives: People with HIV (PWH) experience a greater risk of morbidity and mortality following COVID-19 infection, and poorer immunological responses to several vaccines. We explored existing evidence regarding the immunogenicity, effectiveness, and safety of SARS-CoV-2 vaccines in PWH compared with controls. Methods: We conducted a systematic search of electronic databases from January 2020 until June 2022, in addition to conference databases, to identify studies comparing clinical, immunogenicity, and safety in PWH and controls. We compared results between those with low (<350 cells/μl) and high (>350 cells/μl) CD4+ T-cell counts where possible. We performed a meta-analysis of seroconversion and neutralization responses to calculate a pooled risk ratio as the measure of effect. Results: We identified 30 studies, including four reporting clinical effectiveness, 27 immunogenicity, and 12 reporting safety outcomes. PWH were 3% [risk ratio 0.97, 95% confidence interval (95% CI) 0.95–0.99] less likely to seroconvert and 5% less likely to demonstrate neutralization responses (risk ratio 0.95, 95% CI 0.91–0.99) following a primary vaccine schedule. Having a CD4+ T-cell count less than 350 cells/μl (risk ratio 0.91, 95% CI 0.83–0.99) compared with a CD4+ T-cell count more than 350 cells/μl, and receipt of a non-mRNA vaccine in PWH compared with controls (risk ratio 0.86, 95% CI 0.77–0.96) were associated with reduced seroconversion. Two studies reported worse clinical outcomes in PWH. Conclusion: Although vaccines appear well tolerated in PWH, this group experience poorer immunological responses following vaccination than controls, particularly with non-mRNA vaccines and low CD4+ T-cell counts. PWH should be prioritized for mRNA COVID-19 vaccines, especially PWH with more advanced immunodeficiency.
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