Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery.

OBJECTIVE: To describe the relationship between serum concentration of group B streptococcal capsular polysaccharide-specific immunoglobulin (Ig) G, colonization status, race or ethnicity, and age in pregnant women. METHODS: Pregnant women (n = 3307) were enrolled from geographically and ethnically diverse populations. At the time of admission for delivery, swabs of the lower vagina and rectum were obtained for isolation of group B streptococci. In a subset of women whose sera were available, capsular polysaccharide-specific IgG concentrations were quantified by serotype-specific (Ia, Ib, II, III, and V) enzyme-linked immunosorbent assay and compared by group B streptococcal colonization status. RESULTS: Group B streptococcal colonization was detected in 856 women (26%), and the rate was significantly higher among black women (37%) than in other racial or ethnic groups (odds ratio 1.7, 95% confidence interval 1.4, 2.1). Colonization status did not differ by study site or age. Colonization with serotypes Ia, II, III, or V was associated with significantly higher serum concentrations of IgG specific for the capsular polysaccharide of the colonizing serotype compared with noncolonization. However, 48% of colonized women had low capsular polysaccharide-specific IgG levels (less than 0.5 microg/mL) in their delivery sera. Colonized teenagers had the lowest median concentration. CONCLUSION: Colonization with group B streptococcus can elicit a systemic immune response, with a cumulative increase in the prevalence of capsular polysaccharide-specific IgG with increasing age. Conversely, low antibody levels in colonized teenagers might account in part for the reported increased risk of group B streptococcal disease in neonates born to these patients.

Invasive disease due to group B Streptococcus in pregnant women and neonates from diverse population groups.

From 1993 through 1996, surveillance for invasive disease due to group B Streptococcus (GBS) in neonates aged <7 days and in peripartum pregnant women was performed in a racially and ethnically diverse cohort in 4 cities in the United States. In a birth population of 157,184, 130 neonatal cases (0.8 per 1000) and 54 maternal cases (0.3 per 1000) were identified. Significant correlates with neonatal disease were black or Hispanic race and a birth weight <2500 g. The attack rate for peripartum maternal infection varied widely by city and may have been influenced by the frequency of administration of intrapartum antibiotics or of evaluating febrile women by performance of blood cultures. Pregnancy loss or GBS disease in the infant occurred in 28% of these maternal cases. Among neonatal and maternal GBS isolates, serotypes Ia (34%-37%) and III (25%-26%) predominated, and type V was frequent (14%-23%). These results provide a description of invasive GBS perinatal infection during the period in which guidelines for prevention were actively disseminated.

Structural characteristics of polysaccharides that induce protection against intra-abdominal abscess formation.

Bacteroides fragilis is the anaerobe most commonly isolated from clinical cases of intra-abdominal sepsis. In a rodent model of this disease process, intraperitoneal injection of the capsular polysaccharide complex (CPC) from B. fragilis provokes abscess formation, while subcutaneous administration of this complex confers protection against B. fragilis-induced intra-abdominal abscesses. The CPC consists of two discrete polysaccharides, polysaccharides A and B (PS A and PS B), each possessing oppositely charged structural groups critical to the ability of these carbohydrates to induce the formation of abscesses. Other bacterial polysaccharides that possess oppositely charged groups (such as the group antigen or capsular polysaccharide from Streptococcus pneumoniae type 1 strains) also exhibited potent abscess-inducing capabilities. We report here that positively and negatively charged groups on polysaccharides are also essential for inducing protection against abscess formation. Vaccination of rats with B. fragilis PS A, PS B, or the S. pneumoniae type 1 capsule protected against intra-abdominal abscesses subsequent to intraperitoneal challenge with each of these polysaccharides. Chemical conversion of the free amino or carboxyl groups on PS A to uncharged N-acetyl or hydroxymethyl groups, respectively, abrogated the ability of this polymer to confer protection against polysaccharide-mediated abscess formation. Adoptive transfer of splenic T cells from polysaccharide-vaccinated rats to naive animals demonstrated that T cells mediated this protective activity. T cells transferred from animals vaccinated with a polysaccharide repeating unit (Salmonella typhi Vi antigen) that normally contains one carboxyl group but was chemically converted to a polymer that possesses both free amino and carboxyl groups (accomplished by de-N-acetylating the Vi antigen) protected naive T-cell recipients against polysaccharide-induced abscesses. These results demonstrate that a distinct structural motif associated with the B. fragilis polysaccharides is necessary for induction of protective immunity against abscess formation associated with intra-abdominal sepsis. However, protection is not antigen specific in a traditional sense. Rather, the protective ability of these structurally dissimilar polysaccharides is conferred by, and perhaps specific for, a motif of oppositely charged groups.

Perioperative antibiotic prophylaxis and wound infection following breast surgery.

The effectiveness of perioperative antibiotic prophylaxis against wound infections following breast surgery was investigated by meta-analysis of published data from a randomized clinical trial and an observational data set, which included a total of 2587 surgical procedures, including excisional biopsy, lumpectomy, mastectomy, reduction mammoplasty and axillary node dissection. There were 98 wound infections (3.8%). Prophylaxis was used for 44% (1141) of these procedures, cephalosporins accounted for 986 (86%) of these courses of antibiotics. Prophylaxis prevented 38% of infections, after controlling for operation type, duration of surgery and participation in the randomized trial (Mantel-Haenszel Odds Ratio = 0.62, 95% confidence interval = 0.40-0.95, P = 0.03). There was no significant variation in efficacy according to operation type or duration. We conclude that antibiotic prophylaxis significantly reduces the risk of postoperative wound infection following these commonly performed breast procedures.

Prophylaxis against wound infection following herniorrhaphy or breast surgery.

The effect of perioperative antibiotic prophylaxis on definite wound infections was assessed for 3202 herniorrhaphies or selected breast surgery procedures. Patients were identified preoperatively and monitored for greater than or equal to 4 weeks. Thirty-four percent of patients (1077/3202) received prophylaxis at the discretion of the surgeon; 86 definite wound infections (2.7%) were identified. Prophylaxis recipients were at higher risk for infection, with a higher proportion of mastectomies, longer procedures, and other factors. Patients who received prophylaxis experienced 41% fewer definite wound infections (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.35-0.99; P = .04) and 65% fewer definite wound infections requiring parenteral antibiotic therapy (OR, 0.35; 95% CI, 0.15-0.88; P = .02) after adjustment for duration of surgery and type of procedure. Additional adjustment for age, body mass index, the presence of drains, diabetes, and exposure to corticosteroids did not change the magnitude of this effect meaningfully. The effect of prophylaxis was similar for all procedures studied. In the absence of formal guidelines, surgeons at these institutions administered prophylaxis preferentially to patients at highest risk.

Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery.

We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast, including excision of a breast mass, mastectomy, reduction mammoplasty, and axillary-node dissection. The prophylactic regimen was a single dose of cefonicid (1 g intravenously) administered approximately half an hour before surgery. The patients were followed up for four to six weeks after surgery. Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made. The patients who received prophylaxis had 48 percent fewer probable or definite infections than those who did not (Mantel-Haenszel risk ratio, 0.52; 95 percent confidence interval, 0.32 to 0.84; P = 0.01). For patients undergoing a procedure involving the breast, infection occurred in 6.6 percent of the cefonicid recipients (20 of 303) and 12.2 percent of the placebo recipients (37 of 303); for those undergoing herniorrhaphy, infection occurred in 2.3 percent of the cefonicid recipients (7 of 301) and 4.2 percent of the placebo recipients (13 of 311). There were comparable reductions in the numbers of definite wound infections (Mantel-Haenszel risk ratio, 0.49), wounds that drained pus (risk ratio, 0.43), Staphylococcus aureus wound isolates (risk ratio, 0.49), and urinary tract infections (risk ratio, 0.40). There were also comparable reductions in the need for postoperative antibiotic therapy, non-routine visits to a physician for problems involving wound healing, incision and drainage procedures, and readmission because of problems with wound healing. We conclude that perioperative antibiotic prophylaxis with cefonicid is useful for herniorrhaphy and certain types of breast surgery.

Effect of subinhibitory doses of clindamycin on the virulence of Bacteroides fragilis: role of lipopolysaccharide.

The capsular polysaccharide (CP) of Bacteroides fragilis is an important virulence factor in the formation of experimental intraabdominal abscesses. Incubation of this organism with subinhibitory doses of clindamycin induced morphological changes in the bacteria, including elongation and loss of CP, detected by ferritin-labeled antibody to capsule. Pretreatment of bacteria with subinhibitory doses of clindamycin, however, did not affect the ability of live or heat-killed organisms to produce intraabdominal abscesses in a mouse model of intraabdominal sepsis. Dose-response experiments with purified CP as well as lipopolysaccharide (LPS) from B. fragilis ATCC strain 23745 mixed with sterile cecal contents as adjuvant revealed that both surface components of the organism were capable of causing abscesses in the mouse model. The dose of LPS required to induce abscesses was five times higher than the required dose of CP. Nevertheless, these studies suggested that B. fragilis LPS is another virulence factor in the formation of intraabdominal abscesses.

Cellular control of abscess formation: role of T cells in the regulation of abscesses formed in response to Bacteroides fragilis.

Although abscesses are a major sequela of infection, little is known about which cellular events initiate and which prevent this pathologic response. These studies are the first to indicate a role for T cells in the important pathogenic process of abscess development and also in immunity to abscesses induced by Bacteroides fragilis. We have shown that T cells initiate the formation of abscesses in mice after i.p. challenge with B. fragilis. These T cells bear both Ly-1 and Ly-2 surface markers. Nude mice (which have been shown by others to have T cell or T cell precursors) are also able to form abscesses. Cyclophosphamide-treated mice (with depressed T cell function) were not capable of developing abscesses. Reconstitution with normal or nude mouse spleen cells restored this ability. However, reconstitution with anti-Thy-1.2-treated, anti-Ly-1, or anti-Ly-2-treated spleen cells (or a mixture of the two cell populations) failed to allow abscess formation after bacterial challenge. Immunity to abscesses caused by B. fragilis requires two T cells. The first Ly-1-2+ T cell has an IJ surface marker and has been shown to release a small m.w. soluble factor (ITF) that is antigen specific. Immunity to abscesses, however, depends on the interaction of ITF with a second Ly-1-2+ T cell, demonstrated in reconstitution experiments with nude mice. The data presented document a critical role for T cells in abscess induction and suggest the existence of a suppressor-like T cell circuit in immunity to abscesses.

A soluble suppressor T cell factor protects against experimental intraabdominal abscesses.

This paper describes a suppressor T cell factor which protects mice against intraabdominal abscesses caused by Bacteroides fragilis. This soluble cell-free factor (ITF) is derived from splenic T cells from mice immunized with capsular polysaccharide (CP) of B. fragilis. Mice receiving ITF are protected from developing abscesses caused by B. fragilis to the same degree as animals receiving intact immune splenic T cells. The factor appears to be small in molecular size as protective activity is dialyzable through a 12,000-mol wt exclusion dialysis membrane and is present in fractions intermediate between the bed and void volumes of a P2 Biogel column. The protective effect of ITF is antigen-specific to B. fragilis alone. Mice given a complex inoculum of B. fragilis, enterococcus, and another anaerobe develop abscesses even after receiving column-purified ITF. The activity of ITF also is eliminated after adsorption with B. fragilis CP coupled to sheep erythrocytes but not with an unrelated CP coupled to sheep erythrocytes. ITF, therefore, appears to have a binding site for B. fragilis CP. ITF is heat-labile and loses efficacy after protease digestion, suggesting that the active material is a protein. These studies define a suppressor cell factor with activity in a model system resembling human disease and offer promise for increased understanding of the diversity of cell-mediated immune systems.

Use of a model of intraabdominal sepsis for studies of the pathogenicity of Bacteroides fragilis.

Over the past eight years, a Wistar rat model for intraabdominal sepsis has been developed and used to document the role of obligate anaerobes in this infections. The ability of Bacteroides fragilis alone to provoke abscesses in this model system is due to a species-specific capsular polysaccharide. It has been shown that active immunization of rats with capsular polysaccharide of B. fragilis protects these animals against the development of abscesses after intraperitoneal challenge with this species. Passive transfer of hyperimmune globulin provided protection against B. fragilis bacteremia in nonimmune, challenged animals but did not confer protection against abscess development. Adoptive transfer of spleen cells from immunized to nonimmunized animals resulted in protection against abscess following challenge with B. fragilis, a finding suggesting that a T cell-dependent immune response was involved in protection. It has also been shown that inbred, congenitally athymic OLA/Rnu rats that were actively immunized developed abscesses despite the presence of capsular antibody, as did 100% of unimmunized athymic control rats. However, no phenotypically normal, littermate control rats that were actively immunized developed abscesses. These data suggest that a T cell-dependent immune response is an important part of immunity to B. fragilis. Additional experiments are being performed to better define the immunologic and chemical basis for the protection afforded by immunization.

Evidence for T cell-dependent immunity to Bacteroides fragilis in an intraabdominal abscess model.

It has been shown that active immunization of rats with the capsular polysaccharide of Bacteroides fragilis protects these animals against abscess development following intraperitoneal challenge with this species. Passive transfer of hyperimmune globulin from immunized animals to nonimmune recipients provided protection against B. fragilis bacteremia in challenged animals, but did not confer protection against abscess development. On the other hand, adoptive transfer of spleen cells from immunized animals to nonimmunized recipients resulted in protection against abscesses following challenge with B. fragilis. These data suggested that a T cell-dependent immune response was involved in protection against abscess development after immunization with B. fragilis capsular antigen. To determine the possible role of cell-mediated immunity prompted by the capsular antigen, inbred congenitally athymic OLA/Rnu rats and their phenotypically normal littermates were actively immunized. Despite the development of high titers of anti-B. fragilis capsular antibody, 100% of actively immunized athymic rats developed abscesses, as did 100% of unimmunized athymic control rats. However, no phenotypically normal littermate control rats that were actively immunized developed abscesses, while 100% of phenotypically normal unimmunized rats developed abscesses. Additional studies showed that adoptive transfer of T cell-enriched spleen cell preparations from Wistar/Lewis rats immunized with the capsular polysaccharide to nonimmune recipients also resulted in protection against B. fragilis-induced abscesses. We conclude that the protection afforded by immunization with B. fragilis capsule against intraabdominal abscesses caused by that organism is T cell-mediated and does not require the presence of serum antibody.