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Prophylaxis and treatment of infections complicating abdominal surgery
Journal of Hospital Infection (1992) 22 ( S u p p l e m e n t A), 3-8
Prophylaxis and t r e a t m e n t of infections c o m p l i c a t i n g a b d o m i n a l surgery W. R. W i l s o n a n d F. M o s i m a n n *
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA and *Department of Surgery, University Hospital, Lausanne, Switzerland Summary: T h e suitability of c o m m o n l y used a n t i m i c r o b i a l r e g i m e n s for prophylaxis in a b d o m i n a l surgery and t r e a t m e n t of i n t r a - a b d o m i n a l sepsis is discussed. T h e s e various therapies are often limited in t h e i r usefulness by the range of m i c r o o r g a n i s m s against w h i c h they are effective and thus, to e x t e n d the a n t i m i c r o b i a l cover, agents m a y be c o m b i n e d . S o m e f o r m s of t h e r a p y m a y p r o d u c e adverse effects in susceptible patients, thus l i m i t i n g their use to certain groups, or t h e r e m a y be cost constraints. ~ - l a c t a m a s e - i n h i b i t i n g c o m p o u n d s a p p e a r to offer an optimal c o m b i n a t i o n of a b r o a d s p e c t r u m of activity against aerobic and anaerobic m i c r o o r g a n i s m s , m i n i m a l toxicity and reasonable cost.
Keywords: A n t i m i c r o b i a l prophylaxis; a n t i m i c r o b i a l therapy; i n t r a - a b d o m inal infection.
Introduction
N u m e r o u s studies have demonstrated that the use of parenterally administered prophylactic antimicrobial therapy is not always effective in patients undergoing elective colorectal surgery. 1'2 In these patients, effective prophylaxis m a y be accomplished by preoperative treatment with orally administered, n o n - a b s o r b e d antimicrobial agents which possess activity against aerobic and anaerobic microorganisms, together with the use of a mechanical bowel preparation, such as laxatives and the administration of enemas. However, patients w h o have perforating abdominal trauma with leakage of bowel contents into the peritoneum, peritonitis or other intra-abdominal infection, do benefit from the administration of parenterally administered antimicrobial agents preoperatively. In these cases, however, where there is pre-existing infection, the treatment should be considered to be therapeutic rather than prophylactic. A variety of antimicrobial agents have been used preoperatively in such patients. T h e advantages and disadvantages of a n u m b e r of widely used antimicrobial regimens are discussed below.
Correspondence to: Dr W. R. Wilson, May() Clinic, 200 First Street, Rochester MN 55901, USA. I)195 6701/92/0A0003 + 06 $08,00/0
9 1992 The Hospital Inf':orion Society
3
4
W. R. W i l s o n a n d F. M o s i m a n n
Choices of antimicrobial agents
Aminoglycoside plus clindamycin Aminoglycosides have excellent activity in vitro against most aerobic Gram-negative bacilli. In the past, clindamycin also exhibited high antimicrobial activity in vitro against anaerobic organisms, including Bacteroidesfragilis and B. fragilis group species. Recently, however, studies have demonstrated an increasing resistance of these organisms to clindamycin. 3-6 Wexler et al. reported that clindamycin resistance in B. fragilis ranged from 10-23 % and for B. fragilis group species it ranged from 16-39% (Table I). 3 In this same study, these authors found 19-22% of peptostreptococci to be resistant to clindamycin w h e n tested in vitro. Clindamycin is also inactive against enterococci and thus, enterococcal superinfection may occur in patients treated with combinations of an aminoglycoside and clindamycin. While intra-abdominal infections with Staphylococcus aureus are u n c o m m o n , abdominal w o u n d infections caused by polymicrobial flora, including S. aureus, occur frequently. Clindamycin has variable activity against S. aureus. It is also important to note that such patients might be at risk of aminoglycoside-associated nephrotoxicity or aminoglycosideassociated cranial nerve dysfunction with this therapeutic regimen. .dminoglycoside plus metronidazole Metronidazole exhibits excellent activity in vitro against B. fragilis and B. fragilis group species. Virtually all strains of these microorganisms and peptostreptococci are highly susceptible to metronidazole in vitro. 3 6 While this antimicrobial regimen would provide excellent coverage against aerobic Gram-negative bacilli and anaerobic organisms, it would provide minimal coverage for enterococci or S. aureus infection. T h e same advantages and disadvantages of aminoglycoside therapy would also occur in patients treated with this treatment regimen.
T a b l e I. I n - v i t r o susceptibility of anaerobic isolates* A n t i m i c r o b i a l agent Clindamycin M e t ronidazole T i c a r e i l l i n - c l a v u l a n i c acid Imipenem Cefoxitin Cefonicid * Adapted from Wexler et al. 3
Bacteroidesfragilis 77-90 100 100 100 73-99 3-29
% Susceptibility Bacteroidesfragilis group 61 84 100 98-100 99 100 35-94 4~14
Peptostreptococcus 78 81 100 100 100 92 100
Infections c o m p l i c a t i n g a b d o m i n a l surgery
Cephalosporin In patients with intra-abdominal infections, the use of m o n o t h e r a p y with a cephalosporin that has activity against anaerobes should be avoided. T h e occurrence of cefoxitin-resistant strains of B. fragilis ranges from 1 0 - 2 7 % and for B. fragilis group species from 6 - 6 5 % . 3-~' Ceftizoxime is usually less active than cefoxitin. A m o n g B. fragilis the percentage of ceftizoxime-resistant strains ranged from 5 - 8 7 % and among B. fragilis group species from 8 - 7 4 % . 3 Peptostreptococci are usually inhibited by cefoxitin or ceftizoxime. Cephalosporins are inactive against enterococci and enterococcal superinfection has occurred in patients receiving m o n o t h e r a p y with cephalosporins for intra-abdominal infection. T h e s e cephalosporins also have a low degree of activity against S. aureus and may be inactive against many G r a m - n e g a t i v e bacilli, including Enterobacter, Serratia or Pseudomonas. Additionally, m o n o t h e r a p y with a cephalosporin may result in the emergence of resistant strains of aerobic Gram-negative bacilli. Cephalosporin plus clindamycin or cephalosporin plus metronidazole T h e addition of either clindamycin or metronidazole to therapy with a cephalosporin should enhance the activity against anaerobes. H o w e v e r , neither of these regimens would provide adequate coverage in enterococcal or S. aureus infection. T h e potential for the emergence of resistant aerobic Gram-negative bacilli w o u l d be the same as that for m o n o t h e r a p y with a cephalosporin. Aztreonam plus clindamycin or aztreonam plus metronidazole Aztreonam possesses a narrow spectrum of activity against aerobic Gram-negative microorganisms. It has no activity against G r a m - p o s i t i v e cocci, such as enterococci or S. aureus. While aztreonarn has a spectrum of activity in vitro similar to an aminoglycoside, it is generally less active than an aminoglycoside in vivo against these organisms. Additionally, aztreonam therapy without concomitant aminoglycoside use may result in the emergence of resistant aerobic Gram-negative bacilli, especially Pseudomonas aeruginosa. Imipenem I m i p e n e m shows high antimicrobial efficacy in vitro against 13. Jragilis, peptostreptococci and most other anaerobic microorganisms. 3 (' Additionally, imipenem is active against enterococci, S. aureus and aerobic Gram-negative rods. Emergence of imipenem-resistant microorganisms rarely occurs during therapy. While imipenem is effective therapy for intra-abdominal infections, the principal disadvantages of such treatment are potential toxicity and expense. T h e most c o m m o n serious adverse event associated with imipenem is seizure. 7 This is most likely to occur in patients with a previous
W. R. W i l s o n and F. M o s i m a n n
history of a seizure disorder, cerebral hypoxaemia, elevated serum creatinine or decreased creatinine clearance, previous aminoglycoside therapy, p s e u d o m o n a s infection (a marker for aminoglycoside therapy) and in elderly patients. In many instances, the patients w h o w o u l d benefit the most from i m i p e n e m therapy are the very patients w h o would be most likely to experience a seizure due to the presence of one or more risk factors.
fl-lactamase-inhibiting compounds T h e main advantage for the use of ~-lactamase-inhibiting c o m p o u n d s , e.g. ampicillin-sulbactam, amoxycillin-clavulanic acid or ticarcillin-clavulanic acid, for the prophylaxis and treatment of patients with intra-abdominal infections is the broad spectrum of activity against aerobic Gram-negative bacilli, anaerobic microorganisms, enterococci and S. aureus. Virtually all strains of B. fragilis and B. fragilis group species are susceptible to ampicillin-sulbactam or amoxycillin plus a [3-1actamase-inhibiting c o m p o u n d . 3 T h e ~-lactamase inhibitor combinations exhibit excellent in-vitro antimicrobial activity against peptostreptococci. T h e use of [3-1actamase-inhibiting c o m p o u n d s is associated with fewer adverse events and is less expensive than imipenem therapy. 7 A possible disadvantage of the use of a [3-1actamase-inhibiting c o m p o u n d is the potential for the emergence of resistance in some aerobic Gram-negative bacilli. Ticarcillin-clavulanic acid is more active against some strains of Enterobacteriaceae than ampicillin-sulbactam, including Enterobacter, Klebsiella, Serratia and Citrobacter spp. Additionally, ticarcillin-clavulanic acid is more active against Pseudomonas or Xanthomonas maltophilia, than ampicillin-sulbactam. A recent study compared intravenous amoxycillin-clavulanic acid and gentamicin-clindamycin prophylaxis in over 300 patients undergoing colorectal surgery. T h e results indicated that the 13-1actamase-inhibiting c o m p o u n d was well tolerated and might be more effective in preventing intra-abdominal infections. 8 There are several important advantages of the use of a [~-lactamase-inhibiting c o m p o u n d over treatment with the aforementioned regimens, such as the broad s p e c t r u m of activity they possess against aerobic and anaerobic microorganisms, their minimal toxicity, the convenience of m o n o t h e r a p y and their reasonable cost. Conclusions
T h e significance of the preoperative preparation of the patient should not be forgotten. G o o d surgical techniques, together with appropriate bowel preparation and the administration of systemic antimicrobial agents which ensure effective coverage against anaerobes and G r a m - n e g a t i v e aerobes, will reduce the incidence of postoperative intra-abdominal infections in
Infections complicating abdominal surgery
patients who are at risk of spillage of bowel contents into the peritoneal cavity. Similar antimicrobial cover is required in patients with established intra-abdominal infections. Appropriate choices would include the combination of a cephalosporin with metronidazole or a ~-lactarnaseinhibiting c o m p o u n d with or without an aminoglycoside.
Discussion and audience opinions
In a patient undergoing a cholecystectomy and exploratory abdominal surgery, with subsequent colectomy and appendectomy, what preoperative measures should be undertaken? Audience response. T h e majority of respondents advocated systemic antibiotic prophylaxis, with (38%) or without (24%) mechanical preparation of the colon, before major abdominal surgery. T h e choice of antibiotic cover for operations involving the colon was ranked cephalosporin-metronidazole (39%), aminoglycoside-metronidazole (25%), [3-1actam/13-1actamase inhibitor (21%), first generation cephalosporin (6%) and aminoglycoside alone (3%). I f the above patient developed severe generalized peritonitis, and culture of the peritoneal fluid grew streptococci and P s e u d o m o n a s : what further steps would you take to treat the intra-abdominal infection? Audience response. T h e administration of appropriate systemic antibiotic treatment, with or without other measures, was selected by most respondents (88%), peritoneal lavage with antibiotics was indicated by 17% and the use of topical antibiotics in the w o u n d by 4%. What is your experience with the clinical use of taurolidine? Dr Mosimann. This is a chemotherapeutic agent with anti-endotoxin properties. Its use intravenously in the treatment of peritonitis is complicated by the need for a central line, but we r e c o m m e n d it for peritoneal lavage. Taurolidine has a definite action when used by this route, but the most important element is probably the mechanical rinsing of the abdominal cavity. Is the activity of ticarcillin against enterococci sufficient for its use in abdominal infections? Dr Mosimann. Ticarcillin, as with other extended s p e c t r u m penicillins, is not bactericidal against enterococci b u t will be present at sufficient concentrations to inhibit their growth. Since enterococci are generally present in mixed infections, the use of ticarcillin is appropriate.
W. R. W i l s o n a n d F. M o s i m a n n References
1. Washington JA I I, Dearing WH, Judd ES et al. Effect of pre-operative antibiotic regimen on the development of infection after intestinal surgery: prospective, randomized, double-blind study. ~inn Surg 1974; 180: 567-572. 2. Condon RE, Bartlett JG, Nichols RL et al. Preoperative prophylactic cephalothin fails to control septic complications of colorectal operations: results of a controlled clinical trial. A Veterans Administration Co-operative Study. Am J Surg 1979; 137:68 74. 3. Wexler HM, Molitoris E, Finegold SM. Effect of ~-lactamase inhibitors on the activities of various [~-lactam agents against anaerobic bacteria. Antimicrob Agents Chemother 1991; 35: 1219-1224. 4. Hill GB, Ayers OM, Everett BQ. Susceptibilities of anaerobic Gram-negative bacilli to thirteen antimicrobials and [3-1actamase inhibitor combinations. J Antimicrob Chemother 1991; 28:855 867. 5. Rosenblatt JE. Susceptibility testing of anaerobic bacteria. Clin Lab Med 1989; 9: 239-254. 6. Bourgault AM, Lamothe F, Hoban I)J et al. Survey of Bacteroides fragilis group susceptibility patterns in Canada. Antimicrob Agents Chemother 1992; 36: 343-347. 7. Guess HA, Resseguie LJ, Melton LJ et al. Factors predictive of seizures among intensive care unit patients with gram-negative infections. Epilepsia 1990; 31: 567-573. 8. Mosimann F, Cornu P, Nziya Z. Amoxycillin/clavulanic acid versus gentamicin/clindamycin in elective colorectal surgery: a prospective, comparative, randomised trial. International Congress on the Management of Infection, Amsterdam, April 1992. Abstr. 10A.5.
Prophylaxis and t r e a t m e n t of infections c o m p l i c a t i n g a b d o m i n a l surgery W. R. W i l s o n a n d F. M o s i m a n n *
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA and *Department of Surgery, University Hospital, Lausanne, Switzerland Summary: T h e suitability of c o m m o n l y used a n t i m i c r o b i a l r e g i m e n s for prophylaxis in a b d o m i n a l surgery and t r e a t m e n t of i n t r a - a b d o m i n a l sepsis is discussed. T h e s e various therapies are often limited in t h e i r usefulness by the range of m i c r o o r g a n i s m s against w h i c h they are effective and thus, to e x t e n d the a n t i m i c r o b i a l cover, agents m a y be c o m b i n e d . S o m e f o r m s of t h e r a p y m a y p r o d u c e adverse effects in susceptible patients, thus l i m i t i n g their use to certain groups, or t h e r e m a y be cost constraints. ~ - l a c t a m a s e - i n h i b i t i n g c o m p o u n d s a p p e a r to offer an optimal c o m b i n a t i o n of a b r o a d s p e c t r u m of activity against aerobic and anaerobic m i c r o o r g a n i s m s , m i n i m a l toxicity and reasonable cost.
Keywords: A n t i m i c r o b i a l prophylaxis; a n t i m i c r o b i a l therapy; i n t r a - a b d o m inal infection.
Introduction
N u m e r o u s studies have demonstrated that the use of parenterally administered prophylactic antimicrobial therapy is not always effective in patients undergoing elective colorectal surgery. 1'2 In these patients, effective prophylaxis m a y be accomplished by preoperative treatment with orally administered, n o n - a b s o r b e d antimicrobial agents which possess activity against aerobic and anaerobic microorganisms, together with the use of a mechanical bowel preparation, such as laxatives and the administration of enemas. However, patients w h o have perforating abdominal trauma with leakage of bowel contents into the peritoneum, peritonitis or other intra-abdominal infection, do benefit from the administration of parenterally administered antimicrobial agents preoperatively. In these cases, however, where there is pre-existing infection, the treatment should be considered to be therapeutic rather than prophylactic. A variety of antimicrobial agents have been used preoperatively in such patients. T h e advantages and disadvantages of a n u m b e r of widely used antimicrobial regimens are discussed below.
Correspondence to: Dr W. R. Wilson, May() Clinic, 200 First Street, Rochester MN 55901, USA. I)195 6701/92/0A0003 + 06 $08,00/0
9 1992 The Hospital Inf':orion Society
3
4
W. R. W i l s o n a n d F. M o s i m a n n
Choices of antimicrobial agents
Aminoglycoside plus clindamycin Aminoglycosides have excellent activity in vitro against most aerobic Gram-negative bacilli. In the past, clindamycin also exhibited high antimicrobial activity in vitro against anaerobic organisms, including Bacteroidesfragilis and B. fragilis group species. Recently, however, studies have demonstrated an increasing resistance of these organisms to clindamycin. 3-6 Wexler et al. reported that clindamycin resistance in B. fragilis ranged from 10-23 % and for B. fragilis group species it ranged from 16-39% (Table I). 3 In this same study, these authors found 19-22% of peptostreptococci to be resistant to clindamycin w h e n tested in vitro. Clindamycin is also inactive against enterococci and thus, enterococcal superinfection may occur in patients treated with combinations of an aminoglycoside and clindamycin. While intra-abdominal infections with Staphylococcus aureus are u n c o m m o n , abdominal w o u n d infections caused by polymicrobial flora, including S. aureus, occur frequently. Clindamycin has variable activity against S. aureus. It is also important to note that such patients might be at risk of aminoglycoside-associated nephrotoxicity or aminoglycosideassociated cranial nerve dysfunction with this therapeutic regimen. .dminoglycoside plus metronidazole Metronidazole exhibits excellent activity in vitro against B. fragilis and B. fragilis group species. Virtually all strains of these microorganisms and peptostreptococci are highly susceptible to metronidazole in vitro. 3 6 While this antimicrobial regimen would provide excellent coverage against aerobic Gram-negative bacilli and anaerobic organisms, it would provide minimal coverage for enterococci or S. aureus infection. T h e same advantages and disadvantages of aminoglycoside therapy would also occur in patients treated with this treatment regimen.
T a b l e I. I n - v i t r o susceptibility of anaerobic isolates* A n t i m i c r o b i a l agent Clindamycin M e t ronidazole T i c a r e i l l i n - c l a v u l a n i c acid Imipenem Cefoxitin Cefonicid * Adapted from Wexler et al. 3
Bacteroidesfragilis 77-90 100 100 100 73-99 3-29
% Susceptibility Bacteroidesfragilis group 61 84 100 98-100 99 100 35-94 4~14
Peptostreptococcus 78 81 100 100 100 92 100
Infections c o m p l i c a t i n g a b d o m i n a l surgery
Cephalosporin In patients with intra-abdominal infections, the use of m o n o t h e r a p y with a cephalosporin that has activity against anaerobes should be avoided. T h e occurrence of cefoxitin-resistant strains of B. fragilis ranges from 1 0 - 2 7 % and for B. fragilis group species from 6 - 6 5 % . 3-~' Ceftizoxime is usually less active than cefoxitin. A m o n g B. fragilis the percentage of ceftizoxime-resistant strains ranged from 5 - 8 7 % and among B. fragilis group species from 8 - 7 4 % . 3 Peptostreptococci are usually inhibited by cefoxitin or ceftizoxime. Cephalosporins are inactive against enterococci and enterococcal superinfection has occurred in patients receiving m o n o t h e r a p y with cephalosporins for intra-abdominal infection. T h e s e cephalosporins also have a low degree of activity against S. aureus and may be inactive against many G r a m - n e g a t i v e bacilli, including Enterobacter, Serratia or Pseudomonas. Additionally, m o n o t h e r a p y with a cephalosporin may result in the emergence of resistant strains of aerobic Gram-negative bacilli. Cephalosporin plus clindamycin or cephalosporin plus metronidazole T h e addition of either clindamycin or metronidazole to therapy with a cephalosporin should enhance the activity against anaerobes. H o w e v e r , neither of these regimens would provide adequate coverage in enterococcal or S. aureus infection. T h e potential for the emergence of resistant aerobic Gram-negative bacilli w o u l d be the same as that for m o n o t h e r a p y with a cephalosporin. Aztreonam plus clindamycin or aztreonam plus metronidazole Aztreonam possesses a narrow spectrum of activity against aerobic Gram-negative microorganisms. It has no activity against G r a m - p o s i t i v e cocci, such as enterococci or S. aureus. While aztreonarn has a spectrum of activity in vitro similar to an aminoglycoside, it is generally less active than an aminoglycoside in vivo against these organisms. Additionally, aztreonam therapy without concomitant aminoglycoside use may result in the emergence of resistant aerobic Gram-negative bacilli, especially Pseudomonas aeruginosa. Imipenem I m i p e n e m shows high antimicrobial efficacy in vitro against 13. Jragilis, peptostreptococci and most other anaerobic microorganisms. 3 (' Additionally, imipenem is active against enterococci, S. aureus and aerobic Gram-negative rods. Emergence of imipenem-resistant microorganisms rarely occurs during therapy. While imipenem is effective therapy for intra-abdominal infections, the principal disadvantages of such treatment are potential toxicity and expense. T h e most c o m m o n serious adverse event associated with imipenem is seizure. 7 This is most likely to occur in patients with a previous
W. R. W i l s o n and F. M o s i m a n n
history of a seizure disorder, cerebral hypoxaemia, elevated serum creatinine or decreased creatinine clearance, previous aminoglycoside therapy, p s e u d o m o n a s infection (a marker for aminoglycoside therapy) and in elderly patients. In many instances, the patients w h o w o u l d benefit the most from i m i p e n e m therapy are the very patients w h o would be most likely to experience a seizure due to the presence of one or more risk factors.
fl-lactamase-inhibiting compounds T h e main advantage for the use of ~-lactamase-inhibiting c o m p o u n d s , e.g. ampicillin-sulbactam, amoxycillin-clavulanic acid or ticarcillin-clavulanic acid, for the prophylaxis and treatment of patients with intra-abdominal infections is the broad spectrum of activity against aerobic Gram-negative bacilli, anaerobic microorganisms, enterococci and S. aureus. Virtually all strains of B. fragilis and B. fragilis group species are susceptible to ampicillin-sulbactam or amoxycillin plus a [3-1actamase-inhibiting c o m p o u n d . 3 T h e ~-lactamase inhibitor combinations exhibit excellent in-vitro antimicrobial activity against peptostreptococci. T h e use of [3-1actamase-inhibiting c o m p o u n d s is associated with fewer adverse events and is less expensive than imipenem therapy. 7 A possible disadvantage of the use of a [3-1actamase-inhibiting c o m p o u n d is the potential for the emergence of resistance in some aerobic Gram-negative bacilli. Ticarcillin-clavulanic acid is more active against some strains of Enterobacteriaceae than ampicillin-sulbactam, including Enterobacter, Klebsiella, Serratia and Citrobacter spp. Additionally, ticarcillin-clavulanic acid is more active against Pseudomonas or Xanthomonas maltophilia, than ampicillin-sulbactam. A recent study compared intravenous amoxycillin-clavulanic acid and gentamicin-clindamycin prophylaxis in over 300 patients undergoing colorectal surgery. T h e results indicated that the 13-1actamase-inhibiting c o m p o u n d was well tolerated and might be more effective in preventing intra-abdominal infections. 8 There are several important advantages of the use of a [~-lactamase-inhibiting c o m p o u n d over treatment with the aforementioned regimens, such as the broad s p e c t r u m of activity they possess against aerobic and anaerobic microorganisms, their minimal toxicity, the convenience of m o n o t h e r a p y and their reasonable cost. Conclusions
T h e significance of the preoperative preparation of the patient should not be forgotten. G o o d surgical techniques, together with appropriate bowel preparation and the administration of systemic antimicrobial agents which ensure effective coverage against anaerobes and G r a m - n e g a t i v e aerobes, will reduce the incidence of postoperative intra-abdominal infections in
Infections complicating abdominal surgery
patients who are at risk of spillage of bowel contents into the peritoneal cavity. Similar antimicrobial cover is required in patients with established intra-abdominal infections. Appropriate choices would include the combination of a cephalosporin with metronidazole or a ~-lactarnaseinhibiting c o m p o u n d with or without an aminoglycoside.
Discussion and audience opinions
In a patient undergoing a cholecystectomy and exploratory abdominal surgery, with subsequent colectomy and appendectomy, what preoperative measures should be undertaken? Audience response. T h e majority of respondents advocated systemic antibiotic prophylaxis, with (38%) or without (24%) mechanical preparation of the colon, before major abdominal surgery. T h e choice of antibiotic cover for operations involving the colon was ranked cephalosporin-metronidazole (39%), aminoglycoside-metronidazole (25%), [3-1actam/13-1actamase inhibitor (21%), first generation cephalosporin (6%) and aminoglycoside alone (3%). I f the above patient developed severe generalized peritonitis, and culture of the peritoneal fluid grew streptococci and P s e u d o m o n a s : what further steps would you take to treat the intra-abdominal infection? Audience response. T h e administration of appropriate systemic antibiotic treatment, with or without other measures, was selected by most respondents (88%), peritoneal lavage with antibiotics was indicated by 17% and the use of topical antibiotics in the w o u n d by 4%. What is your experience with the clinical use of taurolidine? Dr Mosimann. This is a chemotherapeutic agent with anti-endotoxin properties. Its use intravenously in the treatment of peritonitis is complicated by the need for a central line, but we r e c o m m e n d it for peritoneal lavage. Taurolidine has a definite action when used by this route, but the most important element is probably the mechanical rinsing of the abdominal cavity. Is the activity of ticarcillin against enterococci sufficient for its use in abdominal infections? Dr Mosimann. Ticarcillin, as with other extended s p e c t r u m penicillins, is not bactericidal against enterococci b u t will be present at sufficient concentrations to inhibit their growth. Since enterococci are generally present in mixed infections, the use of ticarcillin is appropriate.
W. R. W i l s o n a n d F. M o s i m a n n References
1. Washington JA I I, Dearing WH, Judd ES et al. Effect of pre-operative antibiotic regimen on the development of infection after intestinal surgery: prospective, randomized, double-blind study. ~inn Surg 1974; 180: 567-572. 2. Condon RE, Bartlett JG, Nichols RL et al. Preoperative prophylactic cephalothin fails to control septic complications of colorectal operations: results of a controlled clinical trial. A Veterans Administration Co-operative Study. Am J Surg 1979; 137:68 74. 3. Wexler HM, Molitoris E, Finegold SM. Effect of ~-lactamase inhibitors on the activities of various [~-lactam agents against anaerobic bacteria. Antimicrob Agents Chemother 1991; 35: 1219-1224. 4. Hill GB, Ayers OM, Everett BQ. Susceptibilities of anaerobic Gram-negative bacilli to thirteen antimicrobials and [3-1actamase inhibitor combinations. J Antimicrob Chemother 1991; 28:855 867. 5. Rosenblatt JE. Susceptibility testing of anaerobic bacteria. Clin Lab Med 1989; 9: 239-254. 6. Bourgault AM, Lamothe F, Hoban I)J et al. Survey of Bacteroides fragilis group susceptibility patterns in Canada. Antimicrob Agents Chemother 1992; 36: 343-347. 7. Guess HA, Resseguie LJ, Melton LJ et al. Factors predictive of seizures among intensive care unit patients with gram-negative infections. Epilepsia 1990; 31: 567-573. 8. Mosimann F, Cornu P, Nziya Z. Amoxycillin/clavulanic acid versus gentamicin/clindamycin in elective colorectal surgery: a prospective, comparative, randomised trial. International Congress on the Management of Infection, Amsterdam, April 1992. Abstr. 10A.5.