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Ampicillin-chloramphenicol-resistant Haemophilus influenzae: plasmid-mediated resistance in bacterial meningitis
G D Overturf1, D Cable, J Ward
1Department of Pediatrics, University of California, Los Angeles School of Medicine 90024.
Abstract:
A 4-month-old infant with congenital heart disease and sepsis and arthritis, and subsequently meningitis, caused by an antibiotic-resistant strain of Haemophilus influenzae type b, failed to respond to sequential therapy with ampicillin and trimethoprim/sulfamethoxazole. Following treatment with ceftizoxime, the infant was well for 42 days, until he returned to the hospital and died. A total of 10 Haemophilus influenzae type b isolates, all outer membrane protein subtype 51, was isolated from the pretreatment blood and synovium, cerebrospinal fluid and subdural fluids, and the petrous pyramids at autopsy. Pretreatment isolates had no detectable plasmid DNA, chloramphenicol acetyltransferase or beta-lactamase; the minimal inhibitory concentration for ampicillin (AM) and chloramphenicol (CM) was 0.2 and 0.8 microgram/ml, respectively. However, all cerebrospinal fluid isolates had a 42-44 mD plasmid and produced chloramphenicol acetyltransferase and beta-lactamase; the minimal inhibitory concentration of these isolates to AM and CM were 12.5 and 25 micrograms/ml, respectively, and were also resistant to tetracycline and sulfonamide. Resistance to AM and CM was cotransferred by filter-mating conjugation at a frequency of one to two transconjugants per 10(5) to an Rd haemophilus recipient. Posttreatment isolates from the petrous pyramids also were resistant to AM and CM and produced chloramphenicol acetyltransferase and beta-lactamase activity, but had no plasmid DNA. These findings and data from genetic studies suggested that plasmid-bearing antibiotic-resistant Haemophilus influenzae type b was selected from a heterogenous population, and that the AM/CM resistance transposons were incorporated into the bacterial chromosome.
Insights
Antibiotic-resistant Haemophilus influenzae type b emerged in an infant, developing resistance to ampicillin and chloramphenicol. This resistance was linked to plasmid acquisition and chromosomal integration, highlighting challenges in treating severe bacterial infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- A 4-month-old infant with congenital heart disease experienced sepsis, arthritis, and meningitis due to Haemophilus influenzae type b.
- Initial treatment with ampicillin and trimethoprim/sulfamethoxazole was ineffective against the antibiotic-resistant bacteria.
Observation:
- Haemophilus influenzae type b isolates from cerebrospinal fluid exhibited resistance to ampicillin and chloramphenicol.
- These resistant isolates possessed a 42-44 mD plasmid encoding chloramphenicol acetyltransferase and beta-lactamase.
- Resistance determinants were transferable via conjugation, indicating plasmid-mediated spread.
Findings:
- Pre-treatment isolates lacked plasmids and resistance enzymes, while CSF isolates acquired them.
- Post-treatment isolates showed resistance but lacked plasmids, suggesting chromosomal integration of resistance genes.
- Genetic analysis indicated selection of a resistant subpopulation and transposon integration into the bacterial chromosome.
Implications:
- This case highlights the rapid emergence and selection of antibiotic resistance in Haemophilus influenzae type b during infection.
- The findings underscore the importance of monitoring resistance mechanisms, including plasmid-mediated and chromosomal integration.
- Understanding these dynamics is crucial for developing effective therapeutic strategies against resistant bacterial pathogens.