Background <p>Pneumonia, responsible for three&#xa0;million deaths annually worldwide, remains a leading cause of death from hospital-acquired infections. Unfortunately, treatment in most cases is empirical and not based on microbiological data because of difficulty in obtaining reliable lower respiratory tract specimens as they are frequently contaminated by upper respiratory tract bacterial flora. We examined aseptically collected lung specimens from decedents with fatal pneumonia to (a) isolate the multi-drug-resistant gram-negative bacteria (MDR GNB) and analyze their antimicrobial susceptibility profiles and resistance phenotypes to beta-lactams and (b) determine the factors associated with fatal MDR GNB pneumonia.</p> Methods <p>This was a cross-sectional, descriptive autopsy-based study conducted between June-December 2024 at the Mulago National Referral Hospital mortuary and the Clinical Microbiology Laboratory at Makerere University College of Health Sciences, Kampala, Uganda. Deceased adults, within a postmortem interval not exceeding 20&#xa0;hours, with an ante-mortem diagnosis of pneumonia or other lower respiratory tract infections were included. Lung tissue and or aspirates were collected, processed, and analyzed microbiologically for bacterial identification, susceptibility testing, and detection of resistance phenotypes to beta lactams.</p> Results <p>Overall, 120 adults died during hospitalization at Mulago Hospital with a primary diagnosis of pneumonia in the period of June to December 2024; of whom 60/100 (50%) were female. The mean age was 50.2 (16.6) years, and the median duration of hospitalization was 42.5 (Inter-quartile range 19.0–80.0) hours. Nearly half (53/120, 44%) were referrals from private health care facilities while 43 (35.8%) were from public health care facilities. Thirty-two (32/120, 26.7%) were confirmed to be living with HIV and 59/120 (49%) had other co-morbidities. One hundred three (103/120, 85.8%) had received empirical antibiotic treatment without microbiological investigations. Bacteria isolated from lung tissue/aspirates were Klebshiella pneumoniae species in 54(45.0%) patients, Escherichia coli in 33(27.5%), Pseudomonas aeruginosa in 17(14.2%) and Acinetobacter species in 12(10.0%) of the patients. The bacteria isolates were resistant to most of the antibiotics used for empirical therapy with resistance to Ceftriaxone at 86.7%, Piperacillin-tazobactam at 44.2%, Coamoxiclav 46.7% and Meropenem at 21.7%. Amikacin and Tigecycline had the least resistance at 20% and 14.3% respectively. Overall, Cabarpenem resistance (defined by resistance to either Imipenem or Meropenem or Ertapenem) was observed in 60/120 (50%) of patients. Patients who had pneumonia with co-morbidities were 2.5 times more likely to have Cabarpenem resistance; Odds Ratio, OR (95% Confidence interval (CI) 2.51(1.07 to 5.87); p value =0.033 and patients who were referred from private health care facilities were almost 5 times more likely to have Cabarpenem resistance; OR 4.92 (CI 1.35 to 17.9); p-value= 0.016. </p> Conclusion <p>Multidrug resistant gram-negative bacteria were responsible for all fatal bacterial pneumonia during hospitalization. Patients with co-morbidities and referrals from private clinics had higher risk of carbapenem resistance.</p>

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Fatal multi-drug-resistant gram-negative bacterial pneumonia among adults hospitalized àt Mulago National Referral Hospital, Uganda: an autopsy study

  • Wellington Mutumba,
  • Henry Kajumbula,
  • Robert Lukande,
  • Sam Kalungi,
  • Bakeera Semmuli,
  • Grace Banturaki,
  • Damalie Nakanjako

摘要

Background

Pneumonia, responsible for three million deaths annually worldwide, remains a leading cause of death from hospital-acquired infections. Unfortunately, treatment in most cases is empirical and not based on microbiological data because of difficulty in obtaining reliable lower respiratory tract specimens as they are frequently contaminated by upper respiratory tract bacterial flora. We examined aseptically collected lung specimens from decedents with fatal pneumonia to (a) isolate the multi-drug-resistant gram-negative bacteria (MDR GNB) and analyze their antimicrobial susceptibility profiles and resistance phenotypes to beta-lactams and (b) determine the factors associated with fatal MDR GNB pneumonia.

Methods

This was a cross-sectional, descriptive autopsy-based study conducted between June-December 2024 at the Mulago National Referral Hospital mortuary and the Clinical Microbiology Laboratory at Makerere University College of Health Sciences, Kampala, Uganda. Deceased adults, within a postmortem interval not exceeding 20 hours, with an ante-mortem diagnosis of pneumonia or other lower respiratory tract infections were included. Lung tissue and or aspirates were collected, processed, and analyzed microbiologically for bacterial identification, susceptibility testing, and detection of resistance phenotypes to beta lactams.

Results

Overall, 120 adults died during hospitalization at Mulago Hospital with a primary diagnosis of pneumonia in the period of June to December 2024; of whom 60/100 (50%) were female. The mean age was 50.2 (16.6) years, and the median duration of hospitalization was 42.5 (Inter-quartile range 19.0–80.0) hours. Nearly half (53/120, 44%) were referrals from private health care facilities while 43 (35.8%) were from public health care facilities. Thirty-two (32/120, 26.7%) were confirmed to be living with HIV and 59/120 (49%) had other co-morbidities. One hundred three (103/120, 85.8%) had received empirical antibiotic treatment without microbiological investigations. Bacteria isolated from lung tissue/aspirates were Klebshiella pneumoniae species in 54(45.0%) patients, Escherichia coli in 33(27.5%), Pseudomonas aeruginosa in 17(14.2%) and Acinetobacter species in 12(10.0%) of the patients. The bacteria isolates were resistant to most of the antibiotics used for empirical therapy with resistance to Ceftriaxone at 86.7%, Piperacillin-tazobactam at 44.2%, Coamoxiclav 46.7% and Meropenem at 21.7%. Amikacin and Tigecycline had the least resistance at 20% and 14.3% respectively. Overall, Cabarpenem resistance (defined by resistance to either Imipenem or Meropenem or Ertapenem) was observed in 60/120 (50%) of patients. Patients who had pneumonia with co-morbidities were 2.5 times more likely to have Cabarpenem resistance; Odds Ratio, OR (95% Confidence interval (CI) 2.51(1.07 to 5.87); p value =0.033 and patients who were referred from private health care facilities were almost 5 times more likely to have Cabarpenem resistance; OR 4.92 (CI 1.35 to 17.9); p-value= 0.016.

Conclusion

Multidrug resistant gram-negative bacteria were responsible for all fatal bacterial pneumonia during hospitalization. Patients with co-morbidities and referrals from private clinics had higher risk of carbapenem resistance.