1006. Association of Development of Pneumonia and Virulence Gene Expression in Acinetobacter baumannii Isolated from Clinical Specimens

Abstract Background Not all Acinetobacter baumannii isolated from respiratory specimens are true pathogens. Distinguishing between true pathogens and colonizers is important to initiate early treatment and to reduce the unnecessary prescription of antibiotics. To determine the microbiological factors contributing to the development of A. baumannii pneumonia, we investigated the association between the expression level of known A. baumannii virulence genes such as ompA and hisF and pneumonia. Methods Patients in whose respiratory specimens A. baumannii was identified between January 2018 and January 2019 in a tertiary university hospital were recruited into this study. Relevant radiologic findings and more than 5 days of susceptible antibiotic prescription started within 3 days of bacterial isolation were considered as having pneumonia. The absence of radiologic findings of pneumonia until 7 days after the isolation of A. baumannii was defined as colonization. The expression of ompA and hisF was determined with quantitative reverse-transcription polymerase chain reaction. Host factors known to be associated with pneumonia and expression levels of virulent genes were compared between the groups. Results Overall, 246 patients in whose respiratory specimens A. baumannii was identified were recruited into this study. Among them, 17 and 24 patients were assigned to the pneumonia and colonizer groups, respectively. In the univariable analysis, ompA, ICU stay, and mechanical ventilation were significantly associated with pneumonia (p = 0.03, < 0.01, < 0.01 respectively). In the multivariable analysis, mechanical ventilation was significantly associated with pneumonia (OR = 9.75, p = 0.03). ompA expression was not significantly associated with pneumonia in the multivariable analysis (OR = 1.12, p = 0.75) (Table 1). ompA and hisF were significantly associated with the 30-day in-hospital mortality (p = 0.02, < 0.01). Table 1. Univariable and multivariable analysis of factors related to pneumonia Conclusion The association between increased ompA expression in A. baumannii and the development of pneumonia was not statistically significant after adjusting for patient factors. However, the relatively high expression of ompA in pneumonia patients and their association with increased mortality suggests the need for larger-scale prospective studies to draw a conclusion. Disclosures All Authors: No reported disclosures

Background. Not all Acinetobacter baumannii isolated from respiratory specimens are true pathogens. Distinguishing between true pathogens and colonizers is important to initiate early treatment and to reduce the unnecessary prescription of antibiotics. To determine the microbiological factors contributing to the development of A. baumannii pneumonia, we investigated the association between the expression level of known A. baumannii virulence genes such as ompA and hisF and pneumonia.
Methods. Patients in whose respiratory specimens A. baumannii was identified between January 2018 and January 2019 in a tertiary university hospital were recruited into this study. Relevant radiologic findings and more than 5 days of susceptible antibiotic prescription started within 3 days of bacterial isolation were considered as having pneumonia. The absence of radiologic findings of pneumonia until 7 days after the isolation of A. baumannii was defined as colonization. The expression of ompA and hisF was determined with quantitative reverse-transcription polymerase chain reaction. Host factors known to be associated with pneumonia and expression levels of virulent genes were compared between the groups.
Results. Overall, 246 patients in whose respiratory specimens A. baumannii was identified were recruited into this study. Among them, 17 and 24 patients were assigned to the pneumonia and colonizer groups, respectively. In the univariable analysis, ompA, ICU stay, and mechanical ventilation were significantly associated with pneumonia (p = 0.03, < 0.01, < 0.01 respectively). In the multivariable analysis, mechanical ventilation was significantly associated with pneumonia (OR = 9.75, p = 0.03). ompA expression was not significantly associated with pneumonia in the multivariable analysis (OR = 1.12, p = 0.75) ( Table 1). ompA and hisF were significantly associated with the 30-day in-hospital mortality (p = 0.02, < 0.01).

Table 1. Univariable and multivariable analysis of factors related to pneumonia
Conclusion. The association between increased ompA expression in A. baumannii and the development of pneumonia was not statistically significant after adjusting for patient factors. However, the relatively high expression of ompA in pneumonia patients and their association with increased mortality suggests the need for larger-scale prospective studies to draw a conclusion.
Disclosures. Background. Hypermutator (HM) bacteria exhibit high spontaneous mutation rates due to DNA mismatch repair (MMR) gene mutations, which may facilitate antibiotic resistance. HM is best described for chronic infections or colonization, in particular with P. aeruginosa. HM K. pneumoniae (KP) and carbapenem resistant Enterobacterales (CRE) are rarely studied.
Methods. Longitudinal isolates from 5 patients (pts) with long-term ST258 CRKP infections (median: 1.4 yr, 0.5-4.1 yr) underwent Illumina HiSeq whole genome sequencing. Strains from 1 pt were tested for HM and resistance. Mutant strains were created by complementation and CRISPR.
SNP matrix of 11 clinical isolates from a single patient with recurrent KPC-Kp infections The first 6 isolates were recovered within 6 months of transplant (Tinitial). The later 5 isolates were recovered ~40 months after intial GI colonization. Number of SNPs for each pariwise comparision on isolates are shown. Gray highlighted boxes shown SNP defferences between the 5 later strains.
Serial passages of 4 clinical isolates.
T1 and T4 harbored ΔpmutS. Ti=Tinitial (baseline) isolates Conclusion. MMR mutations emerged in longitudinal CRKP, which conferred HM phenotypes and were associated with CAZ and other anti-CRE antibiotic resistance. mutH V76 is crucial in MMR. Long-term colonization or recurrent infections in face of antibiotic exposure might predispose CRKP strains to HM.

Presence of Antibody Dependent Cell Cytotoxicity (ADCC) Functional Antibodies that Target a Complex Gp41 Epitope Correlates with Long-term Nonprogression and ADCC is Maintained with Mutants Using Germline Heavy Chain Variable Gene Sequence of VH1-02 Gene
Sarah Baron, BA 1 ; Meghan Garrett, PhD 2 ; Mark D. Hicar, PhD 1 ; 1 University at Buffalo, Buffalo, New York; 2 University of Washington, Seattle, Washington

Session: P-56. Microbial Pathogenesis
Background. Recent data supports that improved qualitative antibody responses correlate with elite controllers (EC) of HIV. As ADCC has been associated with protection in vaccine studies, thorough exploration of antibodies that facilitate ADCC is warranted. In studies on monoclonal antibodies from long-term non-progressors (LTNPs), our laboratory has previously described highly mutated antibodies against