Komplizierte intraabdominelle Infektionen: Erreger, Resistenzen

Intra-abdominal infections are generally the result of invasion and multiplication of enteric bacteria in the wall of a hollow viscus within the abdomen to produce peritonitis or abscess. When the infection extends into the peritoneal cavity or another normally sterile region of the abdominal cavity, the infection is described as a ?complicated“ intra-abdominal infection. Treatment of patients with complicated intra-abdominal infections involves antimicrobial therapy, generally in conjunction with an appropriate and timely surgical source control. Nearly all intra-abdominal infections are caused by multiple microorganisms that constitute the intestinal flora (aerobes and facultative and obligate anaerobes, with Enterobacteriaceae, enterococci and Bacteroides fragilis isolated most frequently). The emergence of drug resistance (e.g. ESBL-producing Enterobacteriaceae or resistant enterococci and staphylococci) poses a substantial threat to patients with surgical infections. Especially in patients with nosocomially acquired infections inadequate empiric antibiotic treatment is associated with treatment failure and death. In patients at risk broader spectrum antibiotic regimens with coverage of resistant Gram-negative bacilli and anaerobes and Gram-positive bacteria such as enterococci (including VRE) and staphylococci should be considered.     

Intra-abdominal abscesses in children

Forty-one intra-abdominal abscesses in 30 Nigerian children seen over a 2-year period at the Obafemi Awolowo University Teaching Hospital were studied prospectively to determine their location, aetiology, microbiology and clinical course. Thirty-four abscesses (83%) were intraperitoneal with the subphrenic spaces and pelvis being the commonly involved intraperitoneal sites. Six abscesses (15%) were retroperitoneal while there was only one visceral abscess (2%). Diseases of the gastrointestinal tract occurring in 20 patients (67%) were responsible for the majority of intraperitoneal abscesses, while suppurating external iliac adenitis was the major cause of retroperitoneal abscesses. There were 62 microbiological isolates, with 52% being anaerobic bacteria and 47% aerobic bacteria. A fungus, Candida, was isolated once (2%). Escherichia coli and Staphylococcus aureus were the commonest aerobic bacteria, while Bacteroides and anaerobic streptococci were the commonest anaerobes. Sixteen patients (53%) had a mixed flora of aerobic and anaerobic bacteria, while in seven patients each (23%) only aerobic or anaerobic bacteria were isolated. The mortality rate in this series was 23%. Association of an intra-abdominal abscess with remote organ failure, postoperative anastomotic leakage, non-localization of the abscess within the peritoneal cavity and gastrointestinal perforation due to typhoid enteritis was found to portend poor prognosis.     

Bacterial flora of appendicitis in children.

Aerobic and anaerobic cultures were taken immediately upon operative entry to the peritoneal cavity of 114 consecutive children undergoing appendectomy. Stage of appendicitis and clinical presentation could be closely correlated to specific patterns of peritoneal bacterial flora. It was found that appendiceal gangrene and perforation uniformly produce a polymicrobial peritonitis that is based on the symbiosis of aerobes with anaerobes. Ensuing wound and intra-abdominal septic complications were likewise mixed infections. Based on these findings, refinements in the diagnosis of appendiceal gangrene and perforation as well as rationales in the treatment of appendicitis have been discussed.     

Abdominal Drainage Following Appendectomy and Cholecystectomy

Consecutive patients undergoing emergency appendectomy (283) or urgent cholecystectomy (51) were prospectively studied for the development of post-operative incisional or peritoneal sepsis. Severity of the original peritoneal infection was carefully recorded, while use of a Penrose dam to drain the peritoneum was randomized according to pre-assigned hospital number. Both aerobic and anaerobic cultures were taken from the abdomen at the time of operation as well as from all postoperative infectious foci. Results demonstrated no essential differences in incidence of wound and peritoneal infection following appendectomy for simple or suppurative appendicitis (187) or following cholecystectomy for acute cholecystitis (51). However, with gangrenous or perforative appendicitis (94), incisional and intra-abdominal infection rates were 43% and 45%, respectively, when a drain was used; yet only 29 and 13%, respectively, without a drain. These latter differences were significant (p < 0.001). In addition, intra-abdominal abscesses were three times as likely to drain through the incision than along any tract provided by the rubber conduit. Cultures revealed that hospital pathogens accounted for a greater proportion of wound and peritoneal sepsis after cholecystectomy and appendectomy for simple or suppurative appendicitis if a drain had been inserted than if managed otherwise. By contrast, a mixed bacterial flora was responsible for most infections following appendectomy for gangrenous or perforated appendicitis, irrespective as to use of a drain.     

Gas-liquid chromatography for rapid diagnosis of intra-abdominal infection

We assessed the usefulness of gas-liquid chromatography in detecting fecal anaerobes in patients with suspected intra-abdominal infection related to the lower gastrointestinal tract. Twenty-five (89%) of 28 cultures with and five (26%) of 19 cultures without anaerobic isolates were positive for succinate. Data analysis showed that Bacteroides but not Enterobacteriaceae organisms were responsible for succinate production. Volatile acids other than acetate (VAs) were present in 16 (57%) of 28 culture-positive and one (7%) of 14 culture-negative specimens. Sixteen (94%) of 17 VA-positive and seven (28%) of 25 VA-negative specimens had anaerobic isolates shown by culture. The presence of certain VAs was associated with the recovery of specific groups of anaerobic bacteria. The presence of succinate or VA in intra-abdominal fluid provides a specific, useful method for the rapid detection of fecal anaerobes in patients with intra-abdominal infections.     

The infective dose of aerobic and anaerobic bacteria in postoperative wound sepsis

Surgery for perforated appendicitis was used to estimate the infective dose of aerobic and anaerobic bacteria in postoperative wound sepsis. The wound sepsis rates were 22.6% (7/31) after treatment with intravenous ampicillin sodium and metronidazole and 23.5% (8/34) after penicillin G sodium, streptomycin, and metronidazole, a nonsignificant difference. Intraoperative sampling by velvet pads demonstrated that the density of aerobes did not differ significantly from that of anaerobes, either on the surface of the appendix, in peritoneal exudate (aspirated), or in the wound before closure. The predominant pathogens were Escherichia coli and Bacteroides fragilis. In 15 patients who developed wound sepsis, the density of aerobes and anaerobes was significantly higher at all sampling sites than in 50 noninfected patients. The median infective dose of aerobes and anaerobes together was 4.6 X 10(5) colony forming units.cm-2 in the operative wound. There was a significantly high correlation between the densities of bacteria during operation and subsequent wound sepsis.     

Anaerobic infections in surgery: clinical review.

Anaerobic bacteria are being recognized with increasing frequency as important micro-organisms in surgical infections. Clostridium, Bacteriodes, Fusobacterium, and Peptostreptococcus are the clinically prominent pathological anaerobes. All are commensals and, consequently, most anaerobic infections are endogenous in origin. In the colon, anaerobes are 1,000 times more prevalent than aerobes. This has important implications regarding the management of gastrointestinal tract operations and the treatment of infections originating from the bowel. Typical anaerobic infections include gas gangrene, brain abscess, oral infections, putrid lung abscesses, intra-abdominal abscesses, and wound infections following gynecologic and bowel surgery, perirectal abscesses, postabortal infections, and septic thrombophlebitis. Infections with anaerobic organisms must be suspected when there is feculent odor and/or gas production following gynecologic or bowel surgery, when there are organisms on gram staining but no growth on aerobic cultures, or when septicemia is associated with repeatedly negative blood cultures. Debridement and drainage constitute the main stay of treatment. All anaerobes are sensitive to chloramphenicol and clindamycin and all but Bacteroides fragils are sensitive to penicillin. Identification of anaerobes requires proper specimen sampling, immediate culturing on prereduced media, and careful gram staining of clinical material. The frequency of anaerobic organisms in surgical infections generally is not recognized by many surgeons; their importance needs to be stressed in the future.     

Isolation of anaerobic organisms from kidney in serious renal infections

We have studied 45 patients who underwent nephrectomy owing to unilateral renal sepsis for anaerobic and aerobic bacterial growth in the urine and kidney. Anaerobic organisms were recovered from 11 patients: 10 had positive kidney cultures, and only 1 had positive kidney and urine cultures. There was a distinct relationship between anaerobic infection of the kidney and urinary tract obstruction: 44 per cent of the obstructed kidneys yielded anaerobic organisms versus only 11 per cent of the unobstructed kidneys. Bacteroides fragilis was the anaerobic organism most often cultured. It is suggested that cultures for anaerobic organisms be performed together with aerobic cultures in patients with symptomatic upper urinary tract infections associated with urinary obstruction. In patients in whom anaerobic infection is suspected, in spite of negative anaerobic cultures, antibiotic treatment for anaerobes should be added to the existing therapeutic measures.     

Perioperative antibiotic therapy for penetrating injuries of the abdomen.

From 1979 through 1981, 152 patients with penetrating injuries of the intra-abdominal gastrointestinal tract were placed on one of three different perioperative antibiotic regimens in a prospective randomized fashion. The three regimens were A) cefamandole 2 grams every 4 hours, B) cefoxitin 2 grams every 6 hours, and C) ticarcillin 3 grams every 4 hours and tobramycin 1.5 mg/kg every 8 hours. Antibiotics were administered intravenously before and for 48 hours following surgical exploration and repair. The three treatment groups were similar with respect to age, average number of organ injuries, and distribution of organ injuries. Cefoxitin-treated patients experienced uneventful recoveries more often than cefamandole-treated patients (94% vs. 80.3%, p less than 0.05) when the incidence of gram-negative wound infection and intra-abdominal abscess formation was considered, while the number of patients who experienced uneventful recoveries in the ticarcillin-tobramycin group was not statistically different from the other two groups of patients. Bacteroides fragilis was isolated from three of the six abscesses occurring in the cefamandole-treated group, while no anaerobes were isolated from abscesses in patients treated with either of the other two regimens. The results of this study suggest that the most effective perioperative antibiotic regimen for patients with penetrating gastrointestinal wounds should possess activity against both aerobic and anaerobic flora of the bowel.     

Anaerobic infection after total hip replacement. Report of three cases

In a series of 387 consecutive total hip replacements there were nine infections (2.3% infection rate). Three of the infections were caused by an anaerobic gram positive cocci, Peptococcus. This is an increased incidence of infection for this previously rare pathogen. The anaerobic infections occurred despite prophylactic antibiotic coverage with Keflin. No causative factors such as hospital, operating time, operating personnel, medical disease, or blood loss could be associated with the observed anaerobic infections. Two of the anaerobic infections appeared late. This is consistent with other reports of anaerobic infections in implants. Drainage after total hip arthroplasty operation must be cultured for anaerobes as well as aerobes, especially late infections in patients on prophylactic antibiotics. Drainage which is sterile to aerobic culture should alert the physician to a possible anaerobic infection.     

The bacteriology and septic complication of patients with appendicitis.

A detailed bacteriologic study was done on 161 patients operated for appendicitis. Aerobic and anaerobic cultures were taken from the blood, the appendicular lumen, mucosa, serosa, fossa, and from the wound after closure of the peritoneum. There is no correlation between the degree of appendicitis and the incidence of positive blood culture. The infection spread through the appendicular wall as the disease progressed. Aerobic infection was common in early appendicitis but a mixed aerobic and anaerobic infection was predominant in late cases. Late appendicitis, a positive wound culture at the end of the operation, the duration of symptoms of over 36 hours before operation and the age of the patient over 50 years were all associated with an increased incidence of septic complication. From the antibiotic sensitivity on the bacteria isolated, the most effective agent against anaerobes was metronidazole. Effective agents against the aerobes were aminoglycosides and cephalosporins. The best single agent against both anaerobes and aerobes was moxalactum.     

A randomized controlled trial of moxalactam versus clindamycin/tobramycin in the treatment of mixed anaerobic/aerobic infections

Many infections are due to mixtures of facultative gram-negative bacilli and anaerobic bacteria. Moxalactam, a semisynthetic beta lactam antibiotic, is active against a wide range of anaerobic organisms, including most strains of Bacteroides fragilis, as well as many aerobic gram-negative bacilli. We performed a prospective, randomized controlled trial comparing moxalactam alone with the regimen of clindamycin and tobramycin for treatment of mixed aerobic/anaerobic infections. One hundred and six patients with presumed mixed infections were randomized to the study groups. The resultant groups were clinically and microbiologically comparable. The effectiveness of treatment was similar with both antibiotic regimens. Five of 25 patients tested in the moxalactam group had a prolongation of their prothrombin time and one of them developed clinically important bleeding. Two of the 23 patients tested in the clindamycin/tobramycin group had a prolonged prothrombin time with no bleeding. Decreases in hematocrit which could be "probably" or "possibly" related to antimicrobial use were seen in 6 of 48 moxalactam patients and none of 50 clindamycin/tobramycin patients (P = .03). Moxalactam, a potent antimicrobial for both anaerobic and aerobic organisms, demonstrated effectiveness in treating mixed anaerobic/aerobic infections similar to clindamycin/tobramycin but was associated with clinically important decreases in hematocrit.     

Single-dose chemoprophylaxis in elective colorectal surgery. A comparison between doxycycline plus metronidazole and doxycycline.

In a prospective, randomized double-blind study either 400 mg of doxycycline + 1500 mg of metronidazole (D + M) or 400 mg of doxycycline (D) alone were given intravenously as a single preoperative dose to patients admitted for elective colorectal surgery. A comparison of the rate of postoperative septic complications was made. After excluding drop-out patients, 261 patients remained for evaluation. In 135 patients with D + M treatment there were four postoperative septic complications (3.0%). In 126 patients with D treatment 20 septic complications related to the surgical procedure occurred (15.9%). The difference is highly significant (p less than 0.005). Most postoperative infections were superficial wound infections (14 of 24 patients), and the mean hospital stay in the two treatment groups was equal. Bacteriologic studies showed a highly significant reduction in anaerobes in cultures from perioperative intra-abdominal fluid in the D + M treatment group. The study has thus showed that the addition of metronidazole, an efficient agent against anaerobic bacteria, to an antimicrobial agent against aerobic bacteria significantly reduces postoperative septic complications in elective colorectal surgery.     

Anaerobic bacteria in suppurative genitourinary infections

Bacterial growth was obtained from specimens of 55 male and 48 female patients with localized suppurative genitourinary tract infections. The 55 male patients had abscesses of the genitalia (15), scrotal cyst (3), penis (7), testis (6), prostate (3), kidney (4), perinephric area (2) and periurethral area (4), wounds of the scrotum (3) and penis (6), and infected hydrocele (2). The 48 female patients had abscesses of Bartholin's cyst (26), vulva (4), vagina (4), labial cyst (2), kidney (2), perinephric area (1), periurethral area (3) and bladder (2), and a labial wound (4). Anaerobic bacteria only were present in 34 specimens (33 per cent), aerobic bacteria only in 7 (7 per cent), and mixed aerobic and anaerobic flora in 62 (60 per cent). A total of 275 isolates (189 anaerobic and 86 aerobic) was recovered, for an average of 2.6 isolates per specimen (1.8 anaerobes and 0.8 aerobes). The predominant anaerobes recovered were Bacteroides species (103 isolates) and anaerobic cocci (54). The most frequently recovered aerobes were Escherichia coli (26 isolates), Staphylococcus aureus (10) and Proteus species (8). These data illustrate that most suppurative genitourinary infections involve anaerobic bacteria. These findings have important implications regarding the culturing techniques of these infections and for the selection of antimicrobials for their management.     

Open appendectomy for pediatric ruptured appendicitis: a historical clinical review of the prophylaxis of wound infection and postoperative intra-abdominal abscess

Background

We conducted a 3-decade clinical review of prophylaxis for wound infection and postoperative intra-abdominal abscess after open appendectomy for pediatric ruptured appendicitis.

Methods

We reviewed the charts of patients with ruptured appendicitis who underwent open appendectomy performed by the same pediatric surgeon at the Hospital for Sick Children, Toronto, Canada between 1969 and 2003, inclusive. We evaluated 3 types of prophylaxis: subcutaneous (SC) antibiotic powder, peritoneal wound drain and intravenous (IV) antibiotics. We divided the sample into 4 treatment groups: peritoneal wound drain alone (group 1); peritoneal wound drain, SC antibiotic powder and IV antibiotics (group 2); SC antibiotic powder and IV antibiotics (group 3); and IV antibiotics alone (group 4). We used the χ² test with Bonferroni correction for multiple comparisons.

Results

There were 496 patients: 348 (70%) boys and 148 (30%) girls, with a mean age of 7 (range newborn to 17) years. There were 90 (18%) wound infections. Compared with the current standard of practice, IV antibiotics alone (group 4), peritoneal wound drain (group 1) was associated with the lowest number of wound infections (7 [7%], p = 0.023). There were 43 (9%) postoperative intra-abdominal abscesses. Compared with IV antibiotics alone, SC antibiotic powder with IV antibiotics (group 3) was associated with the lowest number of postoperative intra-abdominal abscesses (14 [6%], p = 0.06).

Conclusion

Over a 35-year period of open appendectomy for pediatric ruptured appendicitis, wound infection was least frequent in patients who received prophylactic peritoneal wound drain, and postoperative intra-abdominal abscess was least frequent in those who received prophylactic SC antibiotic powder and IV antibiotics.     

Pre-, intra-, and postoperative antibiotics

Endogenous contamination from perforation or rupture of the gastrointestinal tract; exogenous contamination from missiles, knives, or invasive lines and tubes; and immunodepression related to the severity of injury are responsible for the increased infectious complications noted in patients who have undergone laparotomy for abdominal trauma. Perioperative use of clindamycin and an aminoglycoside, a second- or third-generation cephalosporin, or an enhanced-spectrum penicillin is clearly beneficial in lowering the incidence of intra-abdominal and wound infections. A 12- to 48-hour length of administration of antibiotics after operation is as effective as regimens of longer duration, although presently used dosages may be inadequate in severely injured patients. Adjunctive surgical maneuvers such as peritoneal irrigation with saline-containing antibiotic(s) remain controversial. Perioperative use of antibiotic prophylaxis, coupled with early operation and appropriate surgical technique, results in a 4.4% rate of intra-abdominal abscesses and a 5.1% rate of wound infections after laparotomy for abdominal trauma in modern trauma centers.     

Diffuse peritonitis treated with tobramycin and clindamycin. Bacteria in relation to preoperative duration of illness

Twenty consecutive patients, mean age 71 years, with a peroperative diagnosis of diffuse peritonitis were treated with clindamycin and tobramycin. The aim of this open prospective study was to correlate bacterial findings at operation to the duration of illness. The effectiveness of the treatment was also evaluated. The number of aerobic strains from peritoneal cultures outnumbered anaerobes when duration of illness was less than three days, while the opposite was evident when duration was longer. All isolates were fully susceptible to the antibiotic combination except for four anaerobic strains with MIC greater than 1 mg/l for clindamycin. The response to treatment was good in 18 patients, fair in one and poor in one.     

Comparison of cefuroxime and gentamicin in combination with metronidazole in the treatment of peritonitis due to perforation of the appendix

A study on 42 surgical patients was carried out to find out whether cefuroxime may be substituted for gentamicin in combination with metronidazole in the treatment of peritonitis secondary to perforation of appendix. All patients recovered and there were four wound infections in each group. Both aerobic and anaerobic bacteria were cultured in the peritoneal fluid in 69% of cases and anaerobes only in 19% of the patients. Postoperatively the patients were followed up for one month. The mean length of the hospital stay and convalescence did not differ significantly. There was also no difference in the time to the removal of gastric suction, laboratory measurements and the incidence of pyrexia between the study groups. Although the number of patients was limited the present study indicates that gentamicin may be replaced by less toxic cefuroxime. This is especially the case if there are several risk factors in the use of gentamicin and if there is not a possibility for monitoring the serum levels of gentamicin.     

Comparative analysis of mezlocillin/metronidazole and amoxicillin/clavulanic acid as "one shot" preventive antibiotic administration in colorectal interventions]

The prophylactic effect of intraoperative "one shot" antibiotic application in colorectal surgery was investigated. Patients were randomised and the antibiotic combination Mezlocillin/Metronidazole (group A) or Amoxicillin/Clavulamid acid (group B) was applicated in 160 patients. 111 patients were selected for the study (group A: 59; group B: 52 patients). In the postoperative course 53% (group A) and 67% (group B) of the patients developed bacterial infections. Abdominal wound healing was complicated by infection in 15% (A) and 12% (B) of the patients. A significant difference between the two groups could not be proven, 24% of all patients with documented intraoperative bacterial contamination and 10% of the patients with negative findings developed wound infections. In colorectal surgery patients are still at high risk for infectious complications. Applicated antibiotics should basically cover aerobic and anaerobic germs.     

The consequences of suppression of anaerobic bacteria

Anaerobic bacteria such as Bacteroides fragilis, Peptostreptococcus species, and Fusobacterium species, when accompanied by aerobic bacteria or in the presence of dead tissue, can cause severe infections. This article discusses the most common type of anaerobic infection, i.e., infection after colonic contamination of the abdominal cavity and soft tissues. Colonic anaerobes rarely cause infections as solitary pathogens. Mixed infections of aerobes and anaerobes are treated by source control, surgical drainage and debridement, and combination antibiotic therapy. Antimicrobial treatment should cover both anaerobes and aerobes; treatment of mixed infections with anti-anaerobic agents alone is likely to result in abscess formation. Recent trends toward cost cutting and the advent of antibiotics with good coverage of both aerobes and relevant pathogenic anaerobes have led to increased single-agent therapy with cefoxitin, cefotetan, ampicillin/sulbactam, imipenem/cilastatin, ticarcillin/clavulanate, trovafloxacin/alatrofloxacin, and piperacillin/tazobactam. In the past 15 years, research has begun to focus on the gut barrier, particularly on the beneficial effects of anaerobic microflora. Directing antibiotic therapy against the anaerobe when it is involved in clinical infection is important; however, the negative consequences of anti-anaerobic antibiotic therapy on the beneficial effects of normal distal gut colonization must also be considered.