Pharmacodynamic Effect of Different Dosage Regimes of #Oseltamivir in Severe #Influenza Patients Requiring Mechanical #Ventilation: A Multicentre Randomised Controlled Trial

ABSTRACT

Background and Objectives

This randomised controlled trial evaluated whether higher doses of oseltamivir would improve virological and clinical outcomes in severe influenza patients requiring invasive mechanical ventilation.

Methods

Forty intubated adult patients with severe influenza A or B from four intensive care units in Hong Kong were enrolled and randomised to receive either a double dose (300 mg/day) or a triple dose (450 mg/day) of oseltamivir for 10 days. Baseline data were collected, and outcomes were assessed daily using SOFA and Murray scores. Viral RNA was quantified from nasopharyngeal and tracheal aspirates. The primary outcome was the viral clearance rate after 5 days of treatment; secondary outcomes included 28-day and hospital mortality rates, changes in viral load, and serial SOFA and Murray scores.

Results

Viral clearance rates after 5 days of treatment were low and similar between the double (3/20, 15%) and triple-dose groups (2/20, 10%). No significant differences were observed in 28-day mortality, hospital mortality, ICU length of stay or duration of mechanical ventilation between the double and triple-dose groups. However, patients receiving triple doses exhibited a faster decline in influenza A viral load but had a longer hospital length of stay.

Conclusions

Triple doses of oseltamivir did not significantly improve virological or clinical outcomes compared with double doses in severe influenza.

Source: Influenza and Other Respiratory Viruses, https://onlinelibrary.wiley.com/doi/10.1111/irv.70109

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#Mycoplasma pneumoniae #infection in #adult inpatients during the 2023–24 #outbreak in #France (MYCADO): a national, retrospective, observational study

Summary

Background

An epidemic of Mycoplasma pneumoniae infection has been observed in France since September, 2023. We aimed to describe the characteristics of adults hospitalised for M pneumoniae infection and identify factors associated with severe outcomes of infection.

Methods

MYCADO is a retrospective observational study including adults hospitalised for 24 h or more in 76 hospitals in France for a M pneumoniae infection between Sept 1, 2023, and Feb 29, 2024. Clinical, laboratory, and imaging data were collected from medical records. We identified factors associated with severe outcomes of infection, defined as a composite of intensive care unit (ICU) admission or in-hospital death, using multivariable logistic regression.

Findings

1309 patients with M pneumoniae infection were included: 718 (54·9%) were men and 591 (45·1%) were women; median age was 43 years (IQR 31–63); 288 (22·0%) had chronic respiratory failure; 423 (32·3%) had cardiovascular comorbidities; and 105 (8·0%) had immunosuppression. The most common symptoms were cough (1098 [83·9%]), fever (1023 [78·2%]), dyspnoea (948 [72·4%]), fatigue (550 [42·0%]), expectorations (473 [36·1%]), headache (211 [16·1%]), arthromyalgia (253 [19·3%]), ear, nose, and throat symptoms (202 [15·4%]), diarrhoea (138 [10·5%]), and vomiting (132 [10·1%]). 156 (11·9%) of 1309 patients had extra-respiratory manifestations, including 36 (2·8%) with erythema multiforme, 19 (1·5%) with meningoencephalitis, 44 (3·4%) with autoimmune haemolytic anaemia, and 17 (1·3%) with myocarditis. The median hospital stay was 8 days (IQR 6–11). 424 (32·4%) patients had a severe outcome of infection, including 415 (31·7%) who were admitted to the ICU and 28 (2·1%) who died in hospital. Those more likely to present with severe outcomes of infection were patients with hypertension, obesity, chronic liver failure, extra-respiratory manifestations, pulmonary alveolar consolidation or bilateral involvement on CT scan, as well as elevated inflammatory markers, lymphopenia or neutrophilic polynucleosis, and those who did not versus did receive any antibiotic active against M pneumoniae before admission.

Interpretation

This national, observational study highlighted unexpected, atypical radiological presentations, a high proportion of transfers to the ICU, and an association between severity and delayed administration of effective antibiotics. This should remind clinicians that no radiological presentation can rule out M pneumoniae infection, and encourage them to reassess patients early after prescribing a β-lactam, or even to discuss prescribing macrolides as first-line treatment in the context of an epidemic.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00805-3/abstract?rss=yes

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