A Randomized Clinical Trial of Bayesian-Guided Beta-Lactam Infusion Strategy and Associated Bacterial Resistance and Clinical Outcomes in Patients With Severe Pneumonia.

BACKGROUND: Antimicrobial resistance is a growing health concern worldwide. The objective of this study was to evaluate the effect of beta-lactam infusion on the emergence of bacterial resistance in patients with severe pneumonia in the intensive care unit. METHODS: Adult intensive care patients receiving cefepime, meropenem, or piperacillin-tazobactam for severe pneumonia caused by Gram-negative bacteria were randomized to receive beta-lactams as an intermittent (30 minutes) or continuous (24 hours) infusion. Respiratory samples for culture and susceptibility testing, with minimum inhibitory concentrations (MIC), were collected once a week for up to 4 weeks. Beta-lactam plasma concentrations were measured and therapeutic drug monitoring was performed using Bayesian software as the standard of care. RESULTS: The study was terminated early owing to slow enrollment. Thirty-five patients were enrolled in this study. Cefepime (n = 22) was the most commonly prescribed drug at randomization, followed by piperacillin (n = 8) and meropenem (n = 5). Nineteen patients were randomized into the continuous infusion arm and 16 into the intermittent infusion arm. Pseudomonas aeruginosa was the most common respiratory isolate (n = 19). Eighteen patients were included in the final analyses. No differences in bacterial resistance were observed between arms ( P = 0.67). No significant differences in superinfection ( P = 1), microbiological cure ( P = 0.85), clinical cure at day 7 ( P = 0.1), clinical cure at end of therapy ( P = 0.56), mortality ( P = 1), intensive care unit length of stay ( P = 0.37), or hospital length of stay ( P = 0.83) were observed. Achieving 100% ƒT > MIC ( P = 0.04) and ƒT > 4 × MIC ( P = 0.02) increased likelihood of clinical cure at day 7 of therapy. CONCLUSIONS: No differences in the emergence of bacterial resistance or clinical outcomes were observed between intermittent and continuous infusions. Pharmacokinetic/pharmacodynamic target attainment may be associated with a clinical cure on day 7.

Post-COVID seizure: A new feature of "long-COVID".

Novel coronavirus SARS-CoV-2 has created unprecedented healthcare challenges. Neurologic deficits are often an important presenting symptom. To date, the only reported post-infectious COVID-19 manifestations of neurologic disease include cognitive deficits and dysfunction of the peripheral nervous system. Here we report that seizure can also be a post-COVID-19 or "long-COVID" complication. We present a 71-year-old man with hypertension, diabetes mellitus, and COVID-19 diagnosed by RT-PCR who initially presented with posterior circulation stroke-like symptoms, which completely resolved after emergent thrombolysis. Six days later, the patient returned with seizure activity, supported by radiographic and electroencephalographic studies. Notably, he was negative for SARS-CoV-2, and no other provoking factor was uncovered after a comprehensive work-up. To our knowledge, this is the first report of post-infectious seizures after a case of COVID-19, highlighting the potential importance of monitoring for neurologic symptoms in COVID-19 patients, even after convalescence.

Pseudomonal Meningoencephalitis With Ventriculitis Secondary to Bacteremia in a Burn Patient: A Novel Case.

Burn patients with large burn surface area involvement are at increased risk of infection due to the presence of large wounds, multiple surgeries, prolonged intensive care unit admission, and immunosuppression. Pseudomonas aeruginosa is the most commonly isolated organism in this population. Even with frequent infections in the burn population, meningitis and encephalitis are rare, and ventriculitis is exceptional. We report the case of a 66-year-old woman who developed P. aeruginosa bacteremia during her hospital course, causing secondary meningoencephalitis with ventriculitis. She was admitted for partial- and full-thickness burns affecting the neck, chest, abdomen, upper medial arms, and bilateral anteromedial thighs for an estimated 20% total body surface area burn. She met sepsis criteria and broad-spectrum antimicrobial coverage was initiated. Magnetic resonance imaging of the brain, performed for altered mental status, revealed meningitis and ventriculitis. Cerebrospinal fluid analysis demonstrated findings consistent with bacterial meningitis, with cultures positive for P. aeruginosa. Serial neuroimaging with computerized tomography revealed new areas of ischemia concerning for septic emboli. In the presence of altered mental status and fever of unknown origin, workup should remain broad. Even in the presence of another source, it is important to keep an open mind for the rarer intracerebral infection as it requires different management, including urgent evaluation of antibiotic selection and dosing to ensure central nervous system penetration, and neurosurgical evaluation.

Single-Tablet Combination Therapy for HIV Infection in Pregnancy.

Advances in the management of human immunodeficiency virus infection during pregnancy have led to improved maternal health and significant declines in rates of mother-to-child transmission of human immunodeficiency virus. A critical contributor to this success has been the development of better tolerated, safer, and more convenient antiretroviral medication regimens. Today, 12 fixed-dose, single-tablet combination antiretroviral regimens are available in the United States. These regimens are commonly used in nonpregnant individuals. However, because of altered pharmacokinetics of many drugs during pregnancy and concerns regarding short- and long-term fetal safety, few of these regimens are appropriate for routine use in pregnancy.