Background Microbiologic cure is a common outcome in pneumonia clinical trials, but its clinical significance is incompletely understood. Methods We conducted a retrospective cohort study of adult patients hospitalized with bacterial pneumonia who achieved clinical cure. Rates of recurrent pneumonia and death were compared between patients with persistent growth of the index pathogen at the time of clinical cure (microbiologic failure) and those with pathogen eradication (microbiologic cure). Results Among 441 patients, 237 experienced microbiologic cure and 204 experienced microbiologic failure. Prevalences of comorbidities, ventilator dependence, and severity of acute illness were similar between groups. Patients with microbiologic failure experienced significantly higher rates of recurrent pneumonia or death following clinical cure than patients with microbiologic cure, controlling for comorbid conditions, severity of acute illness, appropriateness of empiric antibiotics, intensive care unit placement, tracheostomy dependence, and immunocompromised status (90-day multivariable adjusted odds ratio [OR], 1.56; 95% confidence interval [CI], 1.04–2.35). This association was observed among patients with pneumonias caused by Staphylococcus aureus (90-day multivariable adjusted OR, 3.69; 95% CI, 1.73–7.90). A trend was observed among pneumonias caused by nonfermenting gram-negative bacilli, but not Enterobacteriaceae or other pathogens. Conclusions Microbiologic treatment failure was independently associated with recurrent pneumonia or death among patients with bacterial pneumonia following clinical cure. Microbiologic cure merits further study as a metric to guide therapeutic interventions for patients with bacterial pneumonia.

BackgroundEpidemiologic studies have linked antibiotic exposure to subsequent sepsis, suggesting that microbiome disruption may be in the causal pathway and an independent risk factor. This study tests whether variation in the gut microbiota associates with risk of sepsis onset and its outcomes.MethodsUsing a validated surveillance definition, patients with an archived rectal swab from intensive care and hematology units were screened for sepsis. After confirmation by chart review, cases were matched to controls in a 1:2 ratio based on age, gender, and collection date. Relative taxon abundance was measured by sequence analysis of 16S rRNA gene amplicons; total bacterial abundance was measured by qPCR of the 23S rRNA gene. Conditional logistic regression identified clinical and microbiota variables associated with sepsis.ResultsThere were 103 sepsis cases matched to 206 controls. In a final model adjusting for exposure to broad-spectrum antibiotics and indwelling vascular catheters, high relative abundance (RA) of Enterococcus (Odds Ratio (OR) 1.36 per 10% increase, P=.016) and high total bacterial abundance (OR 1.50 per 10-fold increase in 23S copies/μL, P =.001) were independently associated with sepsis. Decreased RA of butyrate-producing bacteria also independently associated with sepsis (OR 1.20 for 10% decrease in RA, P =.041), and mortality in unadjusted analysis (OR=1.47 for 10% decrease in RA, P=.034).ConclusionsThis study indicates that the microbiota is altered at sepsis onset. The decreased RA of butyrate-producing bacteria in sepsis also associates with mortality, suggesting a therapeutic role for prebiotics and probiotics in the prevention and treatment of sepsis.ImportanceEarly detection of patients at risk for sepsis could enable interventions to prevent or rapidly treat this life-threatening condition. Prior antibiotic treatment is associated with sepsis, suggesting that disruption of the bacterial population in the gut (the intestinal microbiome) could be an important step leading to disease. To investigate this theory, we matched hospitalized patients with and without sepsis and characterized the patients’ microbiomes close to or at onset of sepsis. We found that several microbiome alterations, including having more total bacteria in the gut was associated with onset, regardless of prior antibiotic treatment. This signature of microbiome disruption brings us closer to identifying the biological causes of sepsis and could be used to develop new diagnostic tests to identify patients at risk of sepsis.

Background Respiratory cultures are often obtained as part of a “pan-culture” in mechanically ventilated patients in response to new fevers or leukocytosis, despite an absence of clinical or radiographic evidence suggestive of pneumonia. Methods This was a propensity score-stratified cohort study of hospitalized mechanically-ventilated adult patients between 2014-2019, with new abnormal temperature or serum white blood cell count (NATW), but without radiographic evidence of pneumonia, change in ventilator requirements or documentation of purulent secretions. Two patient groups were compared: those with respiratory cultures performed within 36 hours following NATW, and those without respiratory cultures performed. The co-primary outcomes were the proportion of patients receiving >2 days of total antibiotic therapy and >2 days of broad-spectrum antibiotic therapy within 1 week following NATW. Results Of 534 included patients, 113 (21.2%) had respiratory cultures obtained and 421 (78.8%) did not. Patients with respiratory cultures performed were significantly more likely to receive antibiotics for >2 days within 1 week following NATW than those without respiratory cultures performed (total antibiotic adjusted odds ratio 2.57, 95% confidence interval 1.39-4.75; broad-spectrum antibiotic adjusted odds ratio 2.47, 95% confidence interval 1.46-4.20). Discussion Performance of respiratory cultures for fever/leukocytosis in mechanically-ventilated patients without increasing ventilator requirements, secretion burden or radiographic evidence of pneumonia was associated with increased antibiotic use within one week following incident abnormal temperature and/or WBC. Diagnostic stewardship interventions targeting performance of unnecessary respiratory cultures in mechanically-ventilated patients may reduce antibiotic overuse within intensive care units.

Purpose To report a case of an adult who developed toxic shock syndrome following COVID-19 infection. Observations A 28-year-old female tested positive for COVID-19. 19 days later, she developed a fever, rash and a burning sensation in both eyes. Her examination revealed mild ocular inflammation with bilateral eyelid and conjunctival involvement. Skin biopsy favored a diagnosis of toxic shock syndrome. She was initiated on corticosteroid eye drops and her ocular symptoms resolved three days later. Conclusion and importance Toxic shock syndrome is almost always associated with conjunctival inflammation. To our knowledge, this is the first report of an adult patient with toxic shock syndrome following COVID-19 infection. The association between toxic shock syndrome and COVID-19 is unclear; however, patients should be vigilant for symptoms as toxic shock syndrome can progress rapidly and cause multi-organ failure.

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Recommended antimicrobial treatment durations for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa have evolved over the past few decades. In this Viewpoint, we provide a narrative review of landmark trials investigating antimicrobial treatment durations for VAP caused by P. aeruginosa, and appraise iterations of expert consensus guidelines based on these data. We highlight strengths and weaknesses of existing data on this topic and provide recommendations for future avenues of study.

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Novel targeted pharmacotherapies have ushered in a new era in the management of chronic lymphocytic leukemia (CLL). Postmarketing surveillance indicates that some of these agents are associated with unexpected increases in opportunistic infections. In this report, we present a case of primary genitourinary invasive aspergillosis in a patient with CLL treated with venetoclax. We briefly review both genitourinary aspergillosis and infection risks associated with venetoclax treatment for CLL.