Bacterial colonization and infection studies in the premature baboon with bronchopulmonary dysplasia

Microbial colonization and infection patterns were prospectively evaluated in premature baboons with and without bronchopulmonary dysplasia (BPD) to assess if prolonged hyperoxia would predispose to a different pattern of microbial colonization and/or a higher risk of respiratory infection. Forty baboons were delivered by hysterotomy at 75% of gestation and randomized into two groups. Group I (control or PRN) animals were placed immediately on high- frequency oscillation at 15 Hz; I:E ratio 1:2, and changed to positive- pressure ventillation at 48 to 72 h. They were maintained on clinically appropriate oxygen at minimal ventilator settings for the remainder of the 21-day experimental period. Group II (oxygen-treated or BPD) animals were ventilated with PPV and FI(O₂) 1.0 for 7 days followed by FI(O₂) 0.8 for 14 days. All animals were treated with antibiotics during some portion of the 21-day course. Specimens from nose, oropharynx, trachea, and rectum were cultured for both aerobes and anaerobes throughout the neonatal intensive care unit (NICU) course. A subset of animals from both groups were killed at 21 days and lung, liver, spleen, and gastric contents were cultured quantitatively at autopsy. Findings showed that coagulase-negative staphylococci were the predominant organisms that colonized the neonate in the NICU. Lung infections were seen to evolve through sequential pathogenetic steps: colonization of the upper respiratory tract, with concomitant or subsequent colonization of the trachea with comparable organism and ultimate recovery of the same organisms at autopsy in the lungs of animals with pneumonia. Although gram-positive bacteria dominated the flora during the first 10 days of the 21-day NICU period, gram-negative organisms became more prevalent during the latter half of the study period. The more severe pneumonias were associated with gram-negative organisms, whereas milder infections were seen in those animals with coagulase-negative staphylococci. We were unable to document that the hyperoxic insult influenced the colonization and infection patterns in these neonates, except for the finding that the more severe histologic pneumonias were seen in the oxygen-treated group. The data suggest that intubation and ventilation alone can lead to abnormal colonization patterns and subsequent infection in neonates receiving prophylactic antibiotics.