Ecological aspects of antimicrobial susceptibility of anaerobic bacteria in Nicaragua
Author: Cáceres, Mercedes
Date: 1999-12-17
Location: Birkeaulan 1, Huddinge sjukhus, F-huset, plan 5
Time: 9.00
Department: Institutionen för immunologi, mikrobiologi, patologi och infektionssjukdomar / Department of Immunology, Microbiology, Pathology and Infectious Diseases
Abstract
Anaerobic bacteria are the predominant constituents of the normal flora
on the skin and the mucous membranes of the human body. They may also act
as potent pathogens in a variety of endogenous infections. Antimicrobial
resistance is an increasing problem with anaerobic and aerobic bacteria.
Different mechanisms for such resistance are known. However,
[beta]-lactamase production is the most common mechanism of resistance.
Emergence of resistant organisms in the normal flora during the
administration of antimicrobial agents has a tremendous impact on the
selection of antimicrobial agents for empirical therapy and is an
important factor in the dissemination of resistant organisms to other
patients. Anaerobic infections are common and frequently associated with
severe morbidity and mortality, so empirical therapy has to be instituted
as early as possible because of delays in obtaining the results of
culture and susceptibility studies. The appropriate therapy should be
based on local susceptibility patterns, as the prevalence of
microorganisms causing infections and the antimicrobial susceptibility
patterns may vary within geographic regions and even within hospitals.
The aims of this thesis are to determine the antimicrobial susceptibility
patterns and [beta]-lactamase production of anaerobic bacteria from the
oral and gastrointestinal microflora of (i) hospitalized antimicrobial
treated adults from Nicaragua and Sweden; (ii) antimicrobial treated and
healthy Nicaraguan children under 2 years of age; (iii) aerobic and
anaerobic bacteria isolated from Nicaraguan patients with mixed
infections; and (iv) to estimate the class-specific antibody response
against Bacteroides fragilis antigens in Nicaraguan and Swedish patients
with intraabdominal infections; and (v) to determine the prevalence of
enterotoxigenic B. fragilis in children with and without diarrhea in
order to provide the physicians with data generated in Nicaragua to
facilitate the selection of antimicrobial therapy.
Bacteroides, Clostridium and Fusobacterium species resistant to at least
one of the following antimicrobials: ampicillin, benzylpenicillin,
piperacillin, cephalotin, cefoxitin and clindamycin, were isolated from
the oral and gastrointestinal microflora of all antimicrobial treated
adults included in this study. The percentage of resistant strains
isolated from the Nicaraguan patients was higher than that found in the
Swedish patients. Bacteroides strains resistant to ampicillin or
cefoxitin were also isolated from the gastrointestinal normal flora of
the children. The percentage of resistance increased with the age of the
children (I month to 2 years of age). The resistant strains were mainly
isolated from antimicrobial treated children. No resistance to cefoxitin
was observed in the strains isolated from the healthy children until they
were 18 months of age.
The antimicrobial susceptibility pattern of anaerobic and aerobic
bacteria isolated from 219 Nicaraguan patients with different infectious
diseases was determined against the most common antimicrobial agents used
in Nicaragua. The B. fragilis group were the most commonly isolated
anaerobes and the most resistant to ampicillin, cefoxitin, and
clindamycin. Only five B. fragilis group strains were resistant to
metronidazole. Fusobacterium strains resistant to ampicillin and
cefoxitin were also isolated. However, no resistance to imipenem and
chloramphenicol was found in these anaerobes. Clostridium,
Peptostreptococcus, Propionibacterium and non-spore forming Gram-positive
rods were sensitive to all the antimicrobial agents tested. Mixed
infections were found in 66% of the patients, mainly from intraabdominal
infections. Together with B. fragilis group strains, Escherichia coli
strains were the most common bacterial association. Ampicillin,
benzylpenicillin, cefoxitin and chloramphenicol were the antimicrobial
agents less active against the E. coli, P. aeruginosa and Klebsiella
strains. Gentamicin, one of the most important antimicrobial agents used,
showed good activity. No more than 18% of the aerobic strains were
resistant. Methicillin resistant Staphylococcus aureus was also common.
No vancomycin resistance was found. Enterotoxigenic B. fragilis strains
were isolated only from children with diarrhea (8.4%) and mainly when
they were less than 2 years of age. All strains were resistant to
ampicillin and one strain was also resistant to clindamycin.
The strongest [beta]-lactamase producers among the anaerobic bacteria
isolated from normal flora and from infected sites were Bacteroides
species followed by Fusobacterium species. Almost all the Gram-negative
aerobic strains and S. aureus strains were [beta]-lactamase producers. A
[beta]-lactamase from B. distasonis strains S:10:7 isolated from the
saliva of a Nicaraguan patient was purified and characterized. The enzyme
had a broad substrate profile, capable of hydrolyzing benzylpenicillin,
ampicillin, piperacillin and cephalotin. No capacity to hydrolyze the
[beta]-lactamase stable compounds cefoxitin and imipenem was observed.
However, the B. distasonis strain S: 10:7 was resistant to cefoxitin. The
enzyme was inhibited by clavulanic acid, sulbactam and tazobactam. The
isoelectric point was 4.6 and the molecular weight 160,000 Daltons.
Elevated IgG titers were mainly seen against the B. fragilis capsular
polysaccharide (CPS) antigens in both groups of patients with
intraabdominal infections, compared with the titers observed against
lipopolysaccharide (LPS) antigens. However, when the titers in Swedish
and Nicaraguan IgG patients were compared, the Swedish titers were higher
than the Nicaraguan titers. Patients with intraabdominal abscess and
perforated appendicitis had the highest antibody responses against the B.
fragilis CPS.
In conclusion, the results of the present investigation show a high level
of resistance and B-lactamase production in Grainnegative anaerobic
bacteria. This may be a reflection of the extensive antibiotic use in
Nicaragua. In spite of these patterns, we can positively state that
therapeutic alternatives are still available for the treatment of
anaerobic bacterial infections because of the good results achieved by
metronidazole, imipenem and chloramphenicol; less active, but still
useful, were cefoxitin and clindamycin.
Issue date: 1999-11-26
Publication year: 1999
ISBN: 91-628-3801-6
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