Unveiling the Hidden Impact: How Biological Sex Influences Acinetobacter baumannii Pneumonia Outcomes
- Ray Sullivan
- Jun 22
- 3 min read

Acinetobacter baumannii is a formidable adversary in healthcare settings, recognized by the World Health Organization as a critical priority pathogen due to its strong association with multidrug-resistant invasive infections and high mortality rates, sometimes reaching 40% to 60%. In 2019, it was the leading bacterial cause of death in four countries, contributing to over 452,000 deaths. Despite its significant global threat, our understanding of how host biological sex influences the course of A. baumannii infections in humans has been limited.
Biological sex refers to variations between males and females stemming from distinct sex chromosomes, which impact immune responses to infection and vaccines. Historically, women have been underrepresented in clinical trials, contributing to knowledge gaps regarding how biological sex affects infectious diseases.
Prior research using mouse models had suggested that female mice were more susceptible to A. baumannii pneumonia, exhibiting decreased survival rates and higher bacterial counts in various tissues. This led researchers to investigate if similar patterns held true for human patients.
A recent retrospective cohort study led by Dane Parker’s Lab at the Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation at Rutgers New Jersey Medical School aimed to address this question. They examined 220 adult patients with A. baumannii pneumonia at a tertiary-care academic center in Newark, NJ. The study aimed to determine if there was a sex bias in patient outcomes by reviewing demographic and clinical data from electronic medical records; it was the first of its kind.
Contrary to the findings in mice, the human data revealed a different story:
Male patients experienced a significantly longer overall length of stay (LOS) in the hospital (median of 32 days for males versus 24 days for females).
Males also had a longer intensive care unit (ICU) LOS (median of 23 days for males versus 17 days for females). The differences were statistically significant.
Younger male patients (18-50 years) had a higher Pneumonia Severity Index (PSI) score upon admission compared to younger females.
For patients over 50 years old, males had a longer median ICU LOS (23 days) compared to females (14 days).
Older males also required more interventions at discharge, such as supplemental oxygen and ventilation, than younger males.
Males were more likely to have evidence of other organisms growing on respiratory cultures, indicating a higher rate of co-infection (71% of males versus 48% of females).
Male patients were more frequently diagnosed with hospital-acquired A. baumannii infections (89% versus 74% in females). Hospital-acquired infections generally lead to worse clinical outcomes.
When stratifying outcomes by the primary reason for hospitalization, the research found that a respiratory primary diagnosis was particularly significant. Males with a respiratory diagnosis had a longer median ICU LOS (24 days) compared to females (13 days).
Despite the differences in LOS and severity, there was no significant difference in overall in-hospital mortality rates between male and female patients (30% for males vs. 26% for females).
The research also highlighted several factors that negatively impact patient outcomes, regardless of sex:
Patients with chronic obstructive pulmonary disease (COPD) had higher mortality rates.
Patients with renal disease also experienced increased mortality rates.
Patients who had recently undergone surgery had longer overall LOS.
Alcohol use within 30 days prior to admission was associated with longer overall and ICU LOS.
Smoking within 30 days prior to admission negatively impacted ICU LOS.
The stark contrast between human and mouse data regarding sex bias in A. baumannii pneumonia outcomes raises important questions. While humanized mouse models might offer increased utility for future research, possible explanations for these differences include hormonal and environmental factors, microbiome-mediated interactions that affect mice and humans differently, and behavioral patterns that vary between sexes.
This groundbreaking study underscores the critical importance of conducting sex- and gender-based studies in infectious diseases. By identifying that men, the elderly, and patients with specific underlying conditions and risk factors experience worse outcomes in A. baumannii pneumonia, the findings can directly guide clinical management strategies during inpatient admission. While the study is limited by its retrospective, single-center design, it provides crucial insights that pave the way for more comprehensive, multi-center, prospective research.
Linz MS, Collins L, Keenan E, Biswas R, Levine D, Mattappallil A, Finkel D, Parker D. Biological sex influences severity and outcomes in Acinetobacter baumannii pneumonia. Microbiol Spectr. 2025 Jun 3;13(6):e0319924. doi: 10.1128/spectrum.03199-24. Epub 2025 Apr 16. PMID: 40237468; PMCID: PMC12131798.
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