[Treatment of complicated anaerobic paraproctitis].
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Organisms of the Bacteroides melaninogenicus and Bacteroides fragilis groups are often found mixed with facultatively anaerobic organisms in infections. The relative importance of these Bacteroides groups and facultative anaerobic pathogens in mixed infections was investigated in a subcutaneous abscess model in mice. This was determined by observing the effect of antimicrobial therapy directed against one or both organisms present in the abscess. Clindamycin or metronidazole was used for treatment of infections caused by Bacteroides species, and either gentamicin, penicillin, ampicillin, or oxacillin was used for treatment of infections caused by facultative flora. In almost all instances the aerobic counterparts in the infection were more important than the unencapsulated Bacteroides species. On the other hand, encapsulated B. melaninogenicus group organisms were found to be more important in abscess formation than were group A streptococci, Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Encapsulated B. fragilis group organisms were found to be more important than or as important as Escherichia coli and group D streptococci and less important than S. aureus, group A streptococci, and K. pneumoniae in induction of subcutaneous abscesses. This study demonstrates that encapsulated Bacteroides species are a factor that should be considered in the treatment of mixed infections with antibiotics.
The in vitro and in vivo activity of metronidazole and spiramycin, used singly or in combination, was tested in the eradication of infection caused by Bacteroides spp. and Neisseria gonorrhoeae alone or in combination. The in vitro tests consisted of determinations of the minimal inhibitory concentrations (MIC), carried out with or without the addition of a constant amount of the other antimicrobials. The MIC of both Bacteroides bivius and Bacteroides fragilis for metronidazole were significantly reduced by the addition of spiramycin (from 0.5 to 0.125 micrograms/ml). The in vivo tests were carried out in mice and consisted of measurements of the effects of the antimicrobial agents on the bacterial contents of abscesses induced by subcutaneous injection of bacterial suspension. Synergism between metronidazole and spiramycin was noted against Bacteroides spp. in abscesses caused by either Bacteroides spp. alone, or in combination with N. gonorrhoeae. Furthermore, an additional reduction in the number of N gonorrhoeae was noted in mixed infection with Bacteroides that was treated with metronidazole alone. This study demonstrates the in vitro and in vivo efficacy of the combination of metronidazole and spiramycin in the treatment of infections caused by either Bacteroides spp. alone or in combination with N. gonorrhoeae.
A mouse model of subcutaneous abscess was used to determine the penetration into the abscess and the preventive value of ofloxacin (Hoe 280). Sterile cecal contents were injected subcutaneously combined with three different types of inoculum: Bacteroides fragilis, Escherichia coli and E. coli plus B. fragilis. For penetration studies three doses of 20 mg/kg of ofloxacin were administered intraperitoneally 8 hourly after abscesses had formed. Serum levels at 10, 20, 30, 60 and 90 min after the last dose showed mean values of: 6.9, 4.7, 3.8, 2.35 and 1.08 mg/l respectively. Simultaneously assessed ofloxacin abscess levels were 3.6, 4.1, 2.4, 1.91 and 1.98 mg/kg. In order to evaluate its preventive value, ofloxacin was given intraperitoneally at doses of 20 mg/kg in four regimens. Regimen A: one dose immediately before injection of the inoculum; regimen B: one dose 4 h after the injection of the inoculum; regimen C: one dose immediately before and two doses 8 h and 16 h after injection of the inoculum and regimen D: one dose 4 h, 12 h and 20 h after injection of the inoculum. The results are expressed as the percentage of the reduction in the number of abscesses formed in the survivors versus the control groups: regimens A) 30 to 70%; B) 0 to 40%; C) 50 to 60%, and D) 10 to 60%. The viable bacterial counts in the abscess contents were also assessed.
This study evaluated sepsis-induced changes in myosin heavy chain (Mhc) protein breakdown and synthesis in rat soleus muscles. Rats were anesthetized and their external jugular veins were cannulated. After 12-16 h, rats were implanted intraabdominally with a sterile fecal pellet, or a pellet containing bacteria (Escherichia coli, 150 CFU and Bacteroides fragilis 10(4) CFU). Thirty hours after implantations, rats were infused with 14C-Leu (60 x 10(3) Bq/h) through the jugular cannula for 4 h. Protein fractional synthetic rate coefficient (FSRC) was determined in muscles of different rat groups. In separate experiments, intact soleus muscles were removed from the three rat groups on days 1 and 2 after implantations, and processed for their wet weight, total protein and Mhc contents. No mortality occurred in sterile-implanted rats. Approximately 40-45% of all septic-implanted rats died on days 1-3, post-implantation. Whereas an approximately 15% (P < 0.01, days 1 or 2) decrease occurred in Mhc content in sterile-implanted rats compared to unoperated controls, septic insult resulted in a greater Mhc loss (a 27% decrease, P < 0.001). Rats' body weight, soleus wet weight and tolat muscle protein changes with sepsis relative to controls were also greater than in the sterile groups. The FSRC value in the septic-implanted rats was significantly lower (P < 0.05) than in non-septic rat muscle. TNF-alpha administration to the septic animals or their treatment with diltiazem did not have a significant effect on FSRC. Overall, these results indicate myosin as a major muscle protein subjected to net catabolism during sepsis, and that the net catabolic response was related to a more pronounced increased in Mhc degradation than the decrease in Mhc synthesis.
OBJECTIVE: To evaluate the role of glutathione metabolising enzymes in rats with Gram-negative sepsis. SETTING: University hospital, Sweden. ANIMALS: 61 male Sprague Dawley rats. INTERVENTIONS: Animals were divided into two groups, one of which was given tert-butyl-4-hydroxyanisole (BHA), a powerful inducer of glutathione metabolising enzymes. A gelatine capsule containing bacteria and adjuvant substances was placed in the abdomen. In one group it contained only adjuvant substances, and the controls underwent sham laparotomy. MAIN OUTCOME MEASURES: Activities of glutathione metabolising enzymes, and histological effect on pulmonary tissue. RESULTS: Activities of glutathione metabolising enzymes were reduced in lung tissue after the induction of sepsis. Pre-treatment with BHA increased enzyme activity and reduced the histological changes. CONCLUSION: Glutathione metabolising enzymes may have a role in sepsis, and pre-treatment with BHA seems to prevent histological changes in pulmonary tissue in septic rats.
Altered glucose metabolism and lactic acidemia are features of Gram-negative polymicrobial abscesses, but the relationship between carbohydrate metabolism and the aerobic or anaerobic organisms is unclear. Since reductions in the % active pyruvate dehydrogenase complex (PDHa) limits glucose oxidation in sepsis, the effect of a 7-day monoclonal (E. coli or B. fragilis) vs. biclonal (E. coli + B. fragilis) intra-abdominal abscess (IA) on PDHa and lactate concentrations in skeletal muscle (SM) and plasma was studied in rats. A chronic IA was created by the intraperitoneal introduction of a sterile rat fecal-agar pellet (1.5 ml) inoculated with a known bacterial flora [sterile (S); E. coli 10(6) CFU/ml (EC); B. fragilis 10(8) CFU/ml (BF); E. coli 10(3) CFU/ml + B. fragilis 10(4) CFU/ml (ECLBF); E. coli 10(3) CFU/ml + B. fragilis 10(8) CFU/ml (ECHBF)]. Neither SM PDHa nor SM nor plasma lactate were altered from control in animals with either sterile (S) or E. coli (EC) monoclonal IA, but SM PDHa was significantly (p less than 0.001) reduced and SM lactate increased (p less than 0.05) in rats with B. fragilis 10(8)/ml (BF) monoclonal IA. In biclonal IA, the effect of sepsis on SM PDHa depended on the concentration of B. fragilis in the IA fluid (ECLBF = 10(4) CFU/ml vs. ECHBF = 10(8) CFU/ml) since the E. coli were constant (10(3) CFU/ml). At the lower B. fragilis IA concentration (ECLBF), the SM PDHa was not different from control. However, when the IA B. fragilis concentration was increased to 10(8) CFU/ml (ECHBF), the SM PDHa was significantly (p less than 0.001) decreased relative to control. A decreased muscle PDHa was always associated with elevated SM and plasma lactate concentrations. These results suggest that IA which permit a threshold of relatively nonlethal (BF = 0% mortality) anaerobic B. fragilis (greater than or equal to 10(8) CFU/ml) to enter the circulation are more important in altering metabolic control of skeletal muscle glucose oxidation and in producing lactic acidemia than are IA with only aerobic E. coli. However, in biclonal intra-abdominal abscesses, B. fragilis potentiated the early mortality from E. coli (EC = 6% vs. ECHBF = 37% mortality), suggesting that the metabolic effect of the B. fragilis-induced lactic acidemia is synergistic with the direct toxic effects of the E. coli.
Immunodiffusion techniques were used on trichloroacetic acid extracts from 10 strains of Bacteroides fragilis in detecting precipitating antibodies against this species in immune rabbit sera. Species and even strain specificities were observed in these precipitin reactions. Multiple antigens were detected in the extracts from some strains, whereas only one precipitin band per extract developed during agar-gel diffusion tests of others. The antigen extracts were found to be both heat stable and resistant to hydrolysis by alpha-chymotrypsin. Four serological patterns were demonstrated in homologous and heterologous reactions with the B. fragilis. antigen-antibody systems used. The results showed that some strains were serologically distinct from others, indicating that the strains tested are of more than one serotype.
A fatal case of meningitis due to Bacteroides fragilis and Fusobacterium necrophorum is reported. This appears to be the first case in which meningitis due to these organisms was not secondary to a disease elsewhere in the body. The organisms are difficult to culture and strict anaerobic methods should be used whenever they are suspected. Intravenous metronidazole is probably the antibiotic of choice.
Sepsis is associated with severe muscle wasting. Mechanisms responsible for sepsis-induced alterations in muscle protein metabolism were investigated in vivo and compared with changes induced by nonseptic inflammation. The rate of protein synthesis in mixed hindlimb muscles was not altered in inflammation but was inhibited 50% in sepsis. This inhibition did not result from a decreased RNA content. Instead, the translational efficiency was significantly reduced by 50% in skeletal muscle of septic animals compared with control. The effect of sepsis to lower the rate of protein synthesis was further examined using individual muscles containing different fiber types. Both the protein concentration and protein synthetic rate in fast-twitch muscles were reduced by sepsis, whereas neither of these parameters was affected in slow-twitch muscles or heart. The decreased translational efficiency did not result from a change in the rate of peptide-chain elongation. Instead, the sepsis-induced inhibition of protein synthesis resulted from a restraint in peptide-chain initiation because sepsis caused a 1.6-fold increase in free ribosomal subunits. Overall, sepsis, but not inflammation, caused an inhibition of protein synthesis primarily in muscles composed of fast-twitch fibers. The mechanism involved in the reduced rates of protein synthesis in muscles resulted from an inhibition of peptide-chain initiation, with no change in peptide-chain elongation.
We examined the effects of TNF-binding protein (TNFBP) on regulatory mechanisms of muscle protein synthesis during sepsis in four groups of rats: Control; Control+TNFBP; Septic; and Septic+TNFBP. Saline (1. 0 ml) or TNFBP (1 mg/kg, 1.0 ml) was injected daily starting 4 h before the induction of sepsis. The effect of TNFBP on gastrocnemius weight, protein content, and the rate of protein synthesis was examined 5 days later. Sepsis reduced the rate of protein synthesis by 35% relative to controls by depressing translational efficiency. Decreases in protein synthesis were accompanied by similar reductions in protein content and muscle weight. Treatment of septic animals with TNFBP for 5 days prevented the sepsis-induced inhibition of protein synthesis and restored translational efficiency to control values. TNFBP treatment of Control rats for 5 days was without effect on muscle protein content or protein synthesis. We also assessed potential mechanisms regulating translational efficiency. The phosphorylation state of p70(S6) kinase was not altered by sepsis. Sepsis reduced the gastrocnemius content of eukaryotic initiation factor 2Bepsilon (eIF2Bepsilon), but not eIF2alpha. The decrease in eIF2Bepsilon content was prevented by treatment of septic rats with TNFBP. TNFBP ameliorates the sepsis-induced changes in protein metabolism in gastrocnemius, indicating a role for TNF in the septic process. The data suggest that TNF may impair muscle protein synthesis by reducing expression of specific initiation factors during sepsis.
The observation that, in rats, metronidazole exhibited antimicrobial activity against resistant Escherichia coli (when this was accompanied by susceptible Bacteroides fragilis) prompted us to attempt to reproduce this phenomenon in another species and under other experimental conditions. In experiment 1, mice injected intraperitoneally with an E. coli/B. fragilis mixture were treated with metronidazole, 250 mg/kg given by mouth at 0 and 10 h, or left untreated. At 24 h, viable counts of bacteria in blood and peritoneal washings were determined. In experiment 2, mice with 5-day-old subcutaneous abscesses containing E. coli and B. fragilis were also either given metronidazole as above or left untreated. At 24 h, viable counts of bacteria in pus were determined. Metronidazole affected neither the frequency with which E. coli persisted at the three sites, nor the viability of E. coli at these sites. This was so despite the fact that, in each of the sites, a significant B. fragilis kill was registered. Thus, pending elucidation of the mechanism by which the phenomenon operates, its non-appearance in these experiments cautions against the extrapolation of the original observations beyond the circumstances under which they were first made.
Transrectal biopsy of the prostate resulted in anaerobic septicemia in two patients, despite parenteral gentamicin sulfate prophylaxis. Bacteroides fragilis sepsis developed subacutely in one patient having a postbiopsy pelvic abscess. Clostridium perfringens sepsis occurred fulminantly in another patient 24 hours after biopsy of a gland extensively involved with adenocarcinoma. These cases indicate a potential hazard of sepsis due to anaerobic contamination with rectal microflora at the time of transrectal prostatic biopsy and the futility of prophylaxis directed only at aerobic bacteria.
We present in this paper a series of cases from our Service of primary abscesses in psoas. We consider the appearance of immunosuppressed patients as a relevant factor of its etiopathogenicity. We believe that a C.A.T. is the best diagnostic method. All three patients that underwent open surgery have had complications. The patients treated with percutaneous puncture has shown a favourable evolution.
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