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PubMedDate not supplied

Immune response in patients with intraabdominal infections treated with imipenem. Swedish Study Group.

In the present investigation the humoral immune response against isolated microorganisms in patients treated with imipenem was studied. Sixty-six patients (34 men and 32 women, 18-86 years of age) with suspicion of intraabdominal infections entered the study. Five patients were excluded for various reasons and the remaining 61 patients were treated with imipenem/cilastatin 0.5-1.0 g t.i.d. for 5-29 days (median nine days). Three serum samples were taken from each patient, the first sample at admission, the second between three and seven days after the first dose of imipenem/cilastatin and the third between 14 and 31 days after the first dose. One third of the patients had a malignant disease and the verified intraabdominal infections were judged to be severe in 23 and moderately severe in 33 of the patients. Fifty-six patients (92%) were cured and five patients (8%) were considered improved after the treatment. The immune response against isolated microorganisms was measured in the three serum samples by indirect immunofluorescence tests and enzyme-linked immunosorbent assays. Among the aerobic microorganisms isolated Escherichia coli (46 strains) Staphylococcus epidermidis (22 strains), Streptococcus milleri (15 strains) and Enterococcus faecalis (11 strains) dominated and among the anaerobic bacteria Bacteroides fragilis (39 strains). Thirty-two patients had significant immune responses against one or more of the isolated microorganisms. E. coli and B. fragilis gave rises in antibody titers in 13 and 20 cases respectively, while significant titers against S. epidermidis were noticed in only three cases, against S. milleri in two cases and against E. faecalis in three cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1994

[Bacteria isolated from intraabdominal infection and their susceptibilities to antimicrobial agents].

Bacteria isolated from intraabdominal infections during the period from July 1982 to June 1993 were investigated with regard to their classifications according to a joint research by 9 university hospitals in Japan. The following results were obtained. 1. A total of 971 strains were isolated from 684 out of 597 patients with peritonitis, and 287 strains out of 971 were isolated from postoperative peritonitis. 2. The most predominant organism isolated from patients with acute peritonitis was Escherichia coli (28%), followed by Bacteroides fragilis group (17%), Gram-positive anaerobic cocci (16%), Enterococcus spp. (9%) and Klebsiella spp. (8%). 3. Against E. coli, cefmenoxime, cefuzonam, cefozopran, aztreonam and carumonam showed MIC50 less than 0.05 micrograms/ml. Against B. fragilis group, erthromycin, clindamycin, imipenem, lincomycin and latamoxef showed MIC50 less than 0.78 micrograms/ml. 4. The most predominant organism isolated from patients with postoperative peritonitis was Enterococcus spp. (20%) and followed by Pseudomonas spp. (14%), and Staphylococcus spp. (13%), E. coli (9%), Enterobacter spp. (8%) and Klebsiella spp. (8%). We suggest that cefazolin, cefmetazole, flomoxef, cefmenoxime, cefuzonam, and latamoxef are the first choice agents in empiric therapy for the treatment of acute peritonitis.

Aged↗

PubMed2005

Current treatment of intraabdominal infections.

Although peritonitis has been recognized as a common and complex disease entity since ancient times, the true understanding and pathophysiology, as well as treatment of peritonitis, continue to plague surgeons and physicians. The clinical course and outcome of peritonitis is dependent upon the struggle between the quantity and virulence of the pathogen and host's physiologic reserve, including the ensuing inflammatory response. The current multimodality treatment of intraabdominal infections is based upon the fundamental principles established by Polk in 1979: surgical source control, fluid resuscitation, adequate nutrition, support of failing organ systems, and antibiotics. Although dramatic advances have been made in the pharmacological treatment of intraabdominal infections, mortality for complicated cases remains high. Consequently, future directions in management of peritonitis may require agents that target specific endotoxin receptors, inflammatory signaling molecules, or immunomodulatory moieties.

Anti-Bacterial Agents↗

PubMed1999

Selective defects of T lymphocyte function in patients with lethal intraabdominal infection.

BACKGROUND: In recent models, compensatory antiinflammatory immune reactions triggered in response to systemic inflammation were considered important for the outcome of sepsis. The present study investigated T-cell functions in patients with postoperative sepsis due to intra-abdominal infection. METHODS: Peripheral T cells were purified from 32 sepsis patients and 41 healthy controls. Proliferation and production of interferon (IFN)-gamma, interleukin (IL)-2, IL-4, tumor necrosis factor (TNF), and IL-10 were stimulated by cross-linking of CD3 and CD28. RESULTS: T-cell proliferation and production of IL-2 and TNF were severely suppressed in patients with lethal intraabdominal infection as compared with survivors and healthy controls. Sepsis survivors showed normal T-cell proliferation and IL-2 release, whereas secretion of TNF was reduced. However, TNF suppression in survivors was less severe than in nonsurviving patients. Defective T-cell functions were observed at the onset of sepsis and persisted throughout the entire observation period. T-cell production of IL-4 and IL-10 was not affected by postoperative intraabdominal infection. CONCLUSIONS: Defective T-cell proliferation and secretion of IL-2 and TNF correlate with sepsis mortality, thus indicating an important role of T 'cells for the immune defense against postoperative infection. Immune defects were evident at the onset of sepsis, suggesting that immunosuppression may develop as a primary response to sepsis without preceding immune hyperactivity.

Abdomen↗

PubMedDate not supplied

Effect of peritoneal fluid pH on outcome of aminoglycoside treatment of intraabdominal infections.

Netilmicin and clindamycin were administered to 47 patients with an intraabdominal infection who underwent emergency laparotomy. Thirty-one patients were cured, seven were improved, and therapy failed in nine patients despite the fact that all aerobic bacteria isolated from these patients were sensitive to netilmicin as determined by standard in vitro susceptibility tests. The pH of peritoneal and drainage fluid collected intraoperatively and during follow-up correlated with clinical outcome. Acidic pH was found in 21 of 33 (64%) specimens sampled from patients with therapeutic failure compared to 17 of 80 (21%) obtained from the categories "cured" and "improved" (p < 0.001). Netilmicin concentrations in serum or peritoneal/drainage fluid did not correlate with clinical outcome. Netilmicin levels were above the minimal inhibitory concentration of the pathogens in 59 of 64 (92%) drainage fluid specimens in which aerobic bacteria were isolated. Aerobic bacteria were isolated in 91% of drainage fluid specimens if the pH was less than 7.0, compared to 37% if pH was more than 7.0 (p < 0.001). Reduction of pH antagonized aminoglycoside activity in vitro against clinical isolates of Escherichia coli. Surgical reexploration should be considered in cases of deterioration following a laparotomy associated with detection of acidic drainage fluid.

Abdomen↗

PubMed1996

Microbiology of intraabdominal infection and contamination.

The processes involved in the genesis of an intraabdominal infection include bacterial contamination, selection, growth, invasion, localisation, and cure or failure. The four flora of abdominal infection (exogenous, gastric, biliary and faecal) are detailed. The author's choice of antibiotic agents for prophylaxis and treatment, and recommendations concerning the duration of treatment are outlined.

Abdomen↗

PubMed1997

Interleukin-10 prevents early cytokine release in severe intraabdominal infection and sepsis.

Early release of macrophage-derived proinflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, are important in the pathogenesis of septic shock and multisystem organ failure in various models of sepsis. IL-10 is a mediator that inhibits cytokine release from activated macrophages. The aim of this study was to determine if IL-10 would decrease serum cytokine elevation in a murine model of cecal ligation and puncture (CLP). CLP in animals is a model that closely mimics the physiologic changes seen in human sepsis. Four groups of 14 female Swiss-Webster mice were used. Group 1 underwent laparotomy alone, groups 2, 3, and 4 underwent laparotomy and CLP. Groups 1 and 2 received intraperitoneal (IP) saline injections to serve as control vehicle. Group 3 (prophylactic) received 10,000 U IP IL-10 1 hr prior to CLP and every 3 hr thereafter. Group 4 (therapeutic) received 10,000 U IP IL-10 1 hr following CLP and every 3 hr thereafter. Animals were sacrificed at 3 and 9 hr following CLP. Serum TNF-alpha, IL-1 beta, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA), CLP produced a significant rise in serum TNF,IL-6, and IL-1 in untreated controls. Prophylactic or therapeutic administration of IL-10 significantly attenuated this early rise in serum cytokines. These results support the hypothesis that (1) CLP produces an early systemic rise in macrophage-derived cytokines and (2) IL-10 given either before or after the onset of CLP-induced intraabdominal infection and sepsis is able to inhibit this early release of macrophage-derived systemic mediators. IL-10 has potential clinical benefits in the therapeutic management of intraabdominal infection and sepsis.

Abdomen, Acute↗

PubMed2004

Surgical approach to the intraabdominal infections.

AIM: The term intraabdominal infectioncomprises a broad of variety of pathological conditions which are characterized by signs of systemic infection as a response to an abdominal source of infection and ranges from a confined problem to a devastating disease regarding all organ systems. Septic abdomen is an interesting challenge in general surgery: to decide when and how to treat septic abdomen lacks of a general consensus and has not been standardized yet. METHODS: A total of 1 110 patients underwent surgical treatment for abdominal infection in a period of 10 years in the Department of Surgery of San Gerardo Hospital, Monza, Italy. We focused our attention on 94 patients who required re-exploration for residual or recurrent intra-abdominal infection. RESULTS: The procedure was associated with a mortality rate of 40%. The median number of re-explorations was 5.1. CONCLUSION: Planned multiple relaparotomies with temporarily abdomen closure are performed only in a selected high mortality risk group of elderly patients with surgical evidence of diffuse peritonitis, presence of primary infectious process of more than 72 hours, and a APACHE II score > 20. Relaparotomy on demand is required instead in those patients who develop a clinical deterioration after a first safe surgical control of the source of infection. Lack of improvement is not considered a condition to reoperate. Early detection of persisting infection, < 24-36 hours, is an important prognostic factor of outcome.

Abdomen↗

PubMedDate not supplied

Intraabdominal infections and gut origin sepsis.

Intraabdominal postoperative or posttraumatic infections remain a major threat to life in spite of generation after generation of increasingly effective antimicrobial drugs indicating the importance of immunological host defense failure following major trauma or surgical complications. The spectrum of infectious postoperative or posttraumatic complications can, in part, be explained by pathogenic factors inherent to the methodology of modern surgical intensive care and techniques. This report presents a survey of the historical background as well as current concepts of the multiple systems organ failure syndrome as related to postoperative or posttraumatic intraabdominal infectious complications. The pathophysiology of nosocomial infectious complications in the intensive care unit setting is analyzed. The concept of "gut origin sepsis" is presented and possible preventive and therapeutic actions discussed. A judicious use of antimicrobial drugs on strict indications is emphasized as is the importance of increased knowledge of the interactions between the gut flora, antibiotics, and absence of enteral nutrition.

Cross Infection↗

PubMed2004

Antimicrobial susceptibility of microorganisms recovered from intraabdominal infections at Belo Horizonte, Brazil.

We evaluated antimicrobial susceptibility patterns of microorganisms isolated from intraabdominal infection of Brazilian patients, by agar dilution, agar diffusion, and E test. Among the strictly anaerobes, 57.7% were resistant to penicillin, 28.2% to clindamycin, and 9.9% to metronidazole. The majority of Escherichia coli and Staphylococcus were sensitive and resistant to almost all drugs, respectively. Half of Candida samples were resistant to itraconazole. Our data reinforce the importance of this kind of study to support rational antimicrobial therapy.

Anti-Infective Agents↗

PubMedDate not supplied

Microbiology in intraabdominal infections: what is the message for clinical studies? (Opinion paper).

Bacterial flora participating in intraabdominal infections are well known. Data are reviewed here documenting the constant antibiotic susceptibility of this flora despite many years of widespread use of antibiotics. The flaws inherent in the concept of "microbiologic efficacy" in evaluating antibiotic efficacy are examined. Among the possible results of a clinical trial, outcomes not in accord with antibiotic sensitivity data occur regularly. Factors such as host defense responses, source control and inoculum density also influence the outcome in a clinical trial but are not currently being measured. Recommendations for improved conduct of trails are made.

Abdomen↗

PubMed1989

Changes of plasma amino acids in total parenteral nutrition-supported patients with intraabdominal infection.

Plasma aminogram changes were prospectively studied in 95 patients with external enteric fistula and intraabdominal infection who were under total parenteral nutrition (TPN) therapy with anfuming 14s. Plasma amino acids and albumin were determined before the administration of TPN, weekly and at the end of the therapy or 2 to 5 days before death of patients. In patients with sepsis and starvation, the aminogram showed remarkably low total free amino acids before TPN therapy. In survivors, free amino acids increased gradually to normal in 2 weeks after use of TPN and in the dead increased rapidly to a significantly high peak at the terminal stage. In both survivors and deceased, phenylalanine level remained high during the study. In response to infection, proline was also elevated but to a lesser degree; the ratio of branched chain amino acid (BCAA) to aromatic amino acid (AAA) was lower than normal and the decrease of arginine was parallel to the severity of infection. We conclude that the ideal amino acid preparation for the starved, septic patients should be high in BCAA and arginine but low in phenylalanine; the administration of inappropriate exogenous amino acids in metabolically decompensated septic patients may bring about more harm than benefit; and in septic patients the persistently elevated level of plasma phenylalanine and proline along with decrease of arginine is a useful prognostic sign.

Amino Acids↗

PubMed1993

Meropenem versus imipenem/cilastatin in the treatment of intraabdominal infections requiring surgery.

In a prospective randomized study meropenem was compared with imipenem/cilastatin in the treatment of 62 patients with intraabdominal infections requiring surgery. The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gallbladder disease. There were 30 patients in the meropenem group and 32 patients in the imipenem/cilastatin group. Both antibiotic regimens were given intravenously at a dosage of 1 g every 8 h for a mean duration of 7.7 days in the meropenem group versus 8.6 days in the imipenem/cilastatin group. Fifty-nine aerobic strains and 15 anaerobic strains were isolated from cultures of pus taken intraoperatively, the meropenem MICs ranging from < or = 0.25 to 2 micrograms/ml. At follow-up at least one month after treatment the outcome was considered successful in all of 27 evaluable patients given meropenem and in all of 29 evaluable patients given imipenem/cilastatin. Both antibiotic regimens were well tolerated.

Adult↗

PubMedDate not supplied

Aztreonam plus clindamycin versus tobramycin plus clindamycin in the treatment of intraabdominal infections.

In a multicenter, randomized clinical trial, aztreonam and tobramycin were compared for efficacy and safety in the treatment of intraabdominal infections. Patients were randomly assigned to one of the drug regimens, and all but two patients were treated concomitantly with clindamycin. Efficacy of treatment could not be evaluated for 107 of the 316 patients enrolled in the study. Among the 209 patients who could be evaluated (104 treated with aztreonam and 105 with tobramycin), microbiologic cure was achieved in 93% and 86%, respectively, and a favorable clinical response was noted in 85% of the patients in both groups. The frequency of adverse drug reactions in the two groups was similar. In this study, the efficacy and safety profiles of aztreonam plus clindamycin were comparable to those of tobramycin plus clindamycin.

Abdomen↗

PubMed2002

Effects of recombinant human growth hormone on rat septic shock with intraabdominal infection by E. coli.

AIM: To investigate the therapeutic effects of recombinant human growth hormone (rhGH) on rat septic shock with intraabdominal infection by E. coli and its possible mechanism. METHODS: 76 SD rats were divided into 3 groups randomly: control group (group C, n=16) without any special treatment, septic shock group (group S, n=30) received bolus injection of E.coli (1X10(10) cfu x L(-1), 15 ml x kg(-1), ip), treated group (group T, n=30) received bolus injection of E.coli, and then followed by rhGH injection (2.25 U x k g(-1) x d(-1), im). Group S and group T were further divided into 1d and 3d subgroups, respectively (n=15 each). Mean arterial pressure (MAP), levels of plasma TNFalpha and endotoxin and leukocyte count were determined on 1st day and 3rd day after E.coli injection. Another 39 SD rats were divided into groups C, S and T (n=13 each) just for observing survival rate within 1 week. RESULTS: (1) On 1st and 3rd day, MAP in group S decreased markedly, and MAP on 1st day lowered more than that of 3rd day (P<0.01), while MAP in group T just decreased slightly. The survival rate within 1 week was much higher in group T (84.6 %) than in group S (46.2 %) (P<0.01). (2)On 1st day, plasma TNFalpha and endotoxin elevated significantly in group S and group T (P<0.05), and endotoxin in group S had more increase (P<0.01). On 3rd day, TNFagr in group S returned to the level of group C (P>0.05),while TNFagr in group T went down below the level of group C(P<0.01). On 3rd day, endotoxin in group S declined, but was still higher than that of group C (P<0.01), endotoxin in group T returned to the level of group C (P>0.05). (3) On 1st day, neutrophil ratio in total leukocyte count in both group S and group T increased significantly (P<0.05 vs group C). CONCLUSION: rhGH showed beneficial effects on rat septic shock. The possible mechanisms may involve the attenuation of bacteria/endotoxin translocation and decreased systemic endotoxin level; inhibition of the production and release of TNFalpha; improved circulatory function; improved systemic host defenses and maintenance of intestinal mucosa barrier.

Abdomen↗

PubMedDate not supplied

High doses of immunoglobulins decrease mortality rate of surgical patients with severe intraabdominal infections and sepsis.

Two groups of 40 surgical Intensive Care Unit patients each, were included in the study. All patients had severe intraabdominal infections and sepsis, and septic score higher than 20. All were treated with individual specified conventional symptomatic therapy, and 40 of them received high doses of intravenous immunoglobulins. Significantly lower mortality rate was noticed in IVIG group (40%) than in control group (63.7%). Immunoglobulin therapy also decreased mortality rate in patients with septic shock, but it was no more effective than conventional therapy in patients with multiple organ failure (MOF).

Abdomen↗

PubMedDate not supplied

Overall clinical experience with aztreonam in the treatment of intraabdominal infections.

Response to aztreonam (1-2 g administered intravenously three or four times daily) was evaluated in a multiclinic study of 113 patients with intraabdominal infections due to gram-negative aerobic organisms. Appropriate therapy with an antibiotic (usually clindamycin) active against gram-positive and/or anaerobic organisms was administered concomitantly for mixed-pathogen infections. A favorable clinical response and microbiologic cure occurred in 90% of the patients treated. All of the 13 patients with infections due to Pseudomonas aeruginosa responded clinically, and 11 of the 13 patients experienced microbiologic cure. In a comparative study, 59 patients were treated with aztreonam and 56 were treated with tobramycin (3-5 mg/kg per day); 95% of the patients in the aztreonam group and 81% of those in the tobramycin group experienced microbiologic cure.

Abdomen↗

PubMed1994

Clindamycin plus amikacin versus clindamycin plus aztreonam in established intraabdominal infections.

BACKGROUND: A prospective, randomized, single-blind study evaluated the efficacy and safety of clindamycin plus amikacin versus clindamycin plus aztreonam (Cl-Az) in treating intraabdominal infections in adults. METHODS: Patients were treated intravenously for 7 to 10 days, clindamycin 900 mg plus amikacin 5.0 mg/kg three times a day or clindamycin 900 mg plus aztreonam 2.0 gm three times a day. All 67 patients enrolled were evaluated for safety and 31 in each group for clinical and microbiologic response. Both groups were similar in initial diagnosis, perforated appendicitis or intraabdominal abscess. In each group 24 patients (77%) were admitted in serious condition and three (10%) in critical condition. Twenty-five patients (80.6%) in each group had aerobic and anaerobic pathogens; the remainder had either aerobic or anaerobic pathogens. RESULTS: On therapy completion, clinical and bacteriologic responses were as follows: clindamycin plus amikacin group, 26 (84%) cured, 3 (9.7%) improved, and 2 (6.3%) failed; Cl-Az group, 25 (80.7%) cured, 6 (19.3%) improved, and 0 failed. Rapid temperature decrease occurred in Cl-Az group (p = 0.007). Forty-one mild adverse medical events reported were evenly distributed, but no patients were removed as a result. CONCLUSIONS: Both combinations were highly effective in managing intraabdominal sepsis. Clindamycin aztreonam showed a slight advantage because of absence of renal toxicity and shorter time to apyrexia.

Abdomen↗