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Abdominal distention and diarrhea in a young female
GRAND ROUNDS
Abdominal Distention and Diarrhea in a Young Female Maj J. Patrick Brooks, USAF, MC,*† Lt Col W. Brian Perry, USAF, MC,† and Melanie L. Richards, MD‡ *379th Air Expeditionary Wing/Expeditionary Medical Group, Al-Udeid Airbase, Qatar, †Wilford Hall Medical Center, San Antonio, Texas; and ‡The University of Texas Health Science Center at San Antonio, San Antonio, Texas PROBLEM: Marked abdominal distention and diarrhea. CLINICAL PRESENTATION: (Dr. J. P. Brooks) A 25year-old woman presented to the emergency department with complaints of abdominal distention, discomfort, and a 2-week history of worsening diarrhea. Her bowel movements ultimately became frequent and watery, but without blood. In the day prior to presentation, her bowel frequency diminished markedly and abdominal distention with discomfort developed. Her medical history was significant only for communityacquired pneumonia 1 month previously. She had no prior surgical procedures. Her only current medication was loperamide, prescribed by her general practitioner during a visit the previous day when her diarrhea was most severe. On further questioning, she recalled taking a brief course of antibiotics for her pneumonia. A computer record search confirmed a 4-day course of oral levofloxacin, 500 mg daily, filled 1 month previously; a chest x-ray at that time confirmed a right basilar pneumonia. Physical examination revealed a slender young female who appeared moderately ill, with a resting tachycardia to the 120s. Cardiovascular examination was unremarkable. The most striking finding was marked abdominal distention, tympany, and moderate, nonlocalized abdominal tenderness without guarding or signs of peritonitis. There were no palpable hernias; rectal examination revealed an empty vault without detectable blood. Laboratory studies were significant for a leukeocytosis (WBC 18,400). An acute abdominal series was notable for air-filled small bowel with air fluid levels and distended, air-filled colon with an ahaustral appearance (Fig. 1). The air terminated abruptly in the descending colon, compatible with colonic obstruction. Computed tomography (CT) was obtained with rectal and IV contrast to evaluate the possible obstruction. Again, Correspondence: Inquiries to Lt Col W. Brian Perry, USAF, MC, Wilford Hall Medical Center, 859 MSGS/MCSG, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236; fax: (210) 292-3893; e-mail: [email protected] The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the United States Government, the Department of Defense, or the Department of the Air Force.
CURRENT SURGERY • Published by Elsevier Inc. on behalf of the Association of Program Directors in Surgery
air-filled small and large bowels were seen with marked abdominal distention. The rectal contrast passed into the descending colon without evidence of obstruction (Fig. 2). There was marked thickening of the rectosigmoid colon. The surgical team was consulted. As obstruction was ruled out, this clinical picture of abdominal distention, thickened colon, and diarrhea represented a form of toxic colitis. Infectious colitis or inflammatory bowel disease were possibilities, but with the history of antibiotic use 1 month previously, toxic Clostridium difficile colitis was favored. The patient was then admitted to the intensive care unit with contact precautions. A nasogastric tube and foley catheter were inserted, and intravenous metronidazole and fluid resuscitation, initiated in the emergency department, was continued. She had not had any further bowel movements since presentation, so toxin assays for Clostridium difficile could not be performed until the next day. Therefore, the patient underwent flexible sigmoidoscopy to confirm the diagnosis that evening in the intensive care unit. Minimal insufflation was used. The rectosigmoid colon was found to be distended and coated in densely adherent, yellow-green mucous (Fig. 3). Copious irrigation was able to reveal inflamed mucosa beneath the pseudomembrane. A fluid sample for fecal leukocytes, culture for fecal pathogens, ova and parasites, and Clostridium difficile toxin was collected. No biopsies were taken. The patient tolerated the limited examination well. With these pathognomonic findings, intravenous metronidazole was continued as severe ileus would likely limit enteric absorption of medications. As a result of her toxic colitis, enteric vancomycin was also administered, via the nasogastric tube. By the next day, the patient had made no improvement in her distention. The fecal leukocyte count was 20, and the Clostridium difficile toxin assay was negative. She was hemodynamically stable with good urine output and no signs of peritonitis. GROUP DISCUSSION: (Dr. W. B. Perry and faculty) This patient with toxic colitis has the potential to become ill and require urgent colectomy. Intensive care unit admission, fluid rescuscitation, bowel rest, and a search for a confirmatory diagnosis are all warranted. Clostridium difficile colitis was fa0149-7944/04/$30.00 doi:10.1016/j.cursur.2004.05.018
435
1. Clostridium difficile-associated diarhea and colitis (Review) Yassin SF, Young-Fadok TM, Zein NN, Pardi DS. Mayo Clin Proc. 2001;76:725-730.
FIGURE 1. Plain abdominal radiograph shows distended small and large bowel.
vored at presentation, and the early use of gentle sigmoidoscopy allowed for early confirmation of that diagnosis. Endoscopic findings consistent with inflammatory bowel disease without a history of antibiotic use would prompt treatment with intravenous steroids and continued close observation. Alternatively, if stool cultures ultimately revealed an infectious colitis other than Clostridium difficile, appropriate therapy could be initiated. In this patient with pseudomembranes on endoscopy, the initial negative Clostridium difficile assay would not change my management. Assuming no worsening condition, peritonitis, or organ system failure, which would prompt operative intervention, I would continue with medical management and submit additional fecal samples for Clostridium difficile toxin testing. LITERATURE UPDATE WITH COMMENTARY: (Dr. J. P. Brooks) Clostridium difficile colitis has been increasing in recent years along with the increasing use of antibiotics. Although most cases are readily treated with cessation of the offending antibiotic and initiation of oral metronidazole, toxic colitis from Clostridium difficile represents the severe end of the spectrum with the potential for perforation, peritonitis, and death. When surgical therapy is required, mortality is still fairly high. We will begin the literature review with an excellent review article from the Mayo Clinic. 436
The incidence of Clostridium difficile colitis is increasing. Although the disease was described before the antibiotic era, Clostridium difficile-associated diarrhea (CDAD) typically occurs after exposure to antibiotics. The most frequent indication for antibiotic use is perioperative prophylaxis, and therefore, surgical patients make up more than half of all patients with CDAD. Any antimicrobial agent can incite the disease, including vancomycin and metronidazole. Clindamycin, lincomycin, ampicillin, or the cephalosporins are involved in the majority of cases. Fluoroquinolones are less likely to cause the disease. Clostridium difficile is present in an asymptomatic carriage stage in 50% of children, but colitis is rare in infants and children possibly because of a higher prevalence of antibodies or immature toxin receptors. Clostridium difficile carriage is uncommon in healthy adults (3% or less), but because it can occur after a single dose of antibiotics, the prevalence in antibiotictreated inpatients is up to 25%. Up to 39% of patients treated with antibiotics will develop some form of antibiotic-associated diarrhea, but Clostridium difficile colitis will be the cause of the diarrhea in only 10% of these patients. Treatment with antimicrobials can alter the balance of normal gut flora and allow overgrowth of Clostridium difficile. The bacteria are noninvasive, so development of colitis is dependent on their ability to produce toxins. Toxin A causes cytotoxicity by disrupting cytoplasmic microfilaments. Toxin B can then enter the cell and cause further toxicity. The damage can range from minimal inflammation of the mucosa to toxic dilation or perforation from inflammation in deeper layers. Clostridium difficile-associated diarrhea usually develops within 2 weeks after initiation of the causative antibiotic, but it can occur at any time within 6 weeks. Profuse, watery diarrhea
FIGURE 2. Abdominal CT scan shows intestinal dilitation without mechanical obstruction.
CURRENT SURGERY • Volume 61/Number 5 • September/October 2004
FIGURE 3. Endoscopic appearance of pseudomembranes.
develops that occasionally contains mucous or blood. The symptoms may be limited to loose stools or progress to abdominal distention, toxic megacolon, sepsis, peritonitis, and multisystem organ failure. Overall mortality is low at 2% to 5%, but with toxic megacolon, mortality ranges from 30% to 80%. Delay in diagnosis of CDAD is associated with higher mortality. Diagnosis of CDAD begins with recognizing the clinical findings as described above, but the disease may occur as an unexplained leukocytosis in an asymptomatic hospitalized patient. The fecal leukocyte count may be elevated. In the appropriate situation, treatment may be initiated prior to confirmatory studies, but typically Clostridium difficile testing will be in order. The enzyme-linked immunosorbent assay (ELISA) for detection of toxin A or B in the stool is preferred at many institutions. Culture for Clostridium difficile is difficult and not specific for active disease. Stool cytotoxicity is considered the gold standard but is expensive and time consuming. To make up for the lower sensitivity of ELISA, up to 3 stool specimens should be tested to increase the sensitivity from 75% to 90%. Endoscopy is beneficial when a quick diagnosis is needed. Although it can be normal in mild disease, patients with more significant CDAD will have erythematous mucosa, progressing to ulcerations and ultimately coalescing exudates of yellowish pseudomembranes. Colonoscopy may be required on occasion when the disease is limited to the proximal colon, beyond the reach of the flexible sigmoidoscope. In patients with severe disease, endoscopy should only be performed by experienced physicians with minimal air insufflation. Treatment begins with supportive therapy, isolation, and discontinuation of the offending antibiotic whenever possible. Neither antidiarrheals nor narcotics should be used, as they may precipitate severe colitis. Metronidazole should be added when therapy is required for significant symptoms or failure of supportive therapy alone. Oral therapy is felt to be superior to the intravenous route. Oral vancomycin is reserved for children,
failure of metronidazole, or severely ill patients. Although metronidazole has comparable efficacy with vancomycin, some Clostridium difficile strains are metronidazole-resistant and vancomycin response rates have been reported at up to 100%. When parenteral therapy is required as a result of ileus, intravenous metronidazole is required, and enteric vancomycin may be added via nasogastric tube or enema if desired. Recurrence of CDAD occurs in 10% to 30% of patients, and it usually responds to metronidazole. With continuing recurrences, prolonged courses of vancomycin may be used. Another option is pulse therapy—alternating treatment for 5 to 7 days of antibiotics with 5- to 7-day periods without antibiotics. Surgical treatment of CDAD is required in 5% or less and can have a high mortality. Total abdominal colectomy with end ileostomy is the procedure of choice. The surgical treatment of this disease is discussed in the following article. 2. Timing of surgery for fulminating pseudomembranous colitis Synnott K, Mealy K, Merry C, Kyne L, Keane C, Quill R. Br J Surg. 1998;85:229-231. At the time of publication of this article, per their review, there had been less than 50 reported cases of fulminant clostridial colitis requiring colectomy, with a collective mortality of 35%. The authors reviewed their experience during an outbreak of CDAD in St. James’s Hospital, Dublin, Ireland. Toxin assays were positive in 138 patients during a 6-month period. Nine of these patients died, 4 of 5 whom required surgery versus 5 of 133 requiring only medical treatment. Indications for surgical treatment of CDAD were (1) peritonitis, (2) shock, (3) multisystem organ failure, and (4) progression of disease despite maximal Clostridium difficile antibiotic therapy. Two of the surgical patients were relapses from prior treatment. Three patients had flexible sigmoidoscopy showing characteristic pseudomembranes. Subtotal abdominal colectomy with end ileostomy was performed in all 5 surgical patients. In 3 patients, a distal mucous fistula was used to allow irrigation of the rectal stump with antibiotics. Operative findings invariably included ascites, a markedly distended and edematous colon without serosal inflammation, and severe mucosal ulceration of the opened specimen. Postoperative death occurred as a result of persistant respiratory failure, myocardial infarction, and in 2 patients as a result of progressive multisystem organ failure. The last surgical patient recovered fully and was the only survivor and the youngest of the group. It was felt that the advanced age of these patients (average 69 years) and accompanying comorbidities contributed to the unusually high mortality. The authors also suggest that improved awareness of the potentially fatal nature of the disease late in the outbreak period may have contributed to early consultation and survival in the fifth operative patient. Based on their experience, they recommend joint medical and
CURRENT SURGERY • Volume 61/Number 5 • September/October 2004
437
surgical management for fulminating Clostridium difficile colitis and favor earlier operative intervention before organ failure develops. The following paper addresses the issue of intravenous metronidazole for CDAD. 3. Intravenous metronidazole for the treatment of clostridium difficile colitis Friedenberg F, Fernandez A, Kaul V, Niami PR, Levine GM. Dis Colon Rectum. 2001;44:11761180. Oral therapy for CDAD with metronidazole or vancomycin is the favored route for treatment, but occasionally nausea, vomiting, or ileus precludes the enteric route. Intravenous metronidazole has been reported as an alternative treatment in case series, but there is a lack of rigorous data. The authors of this article therefore retrospectively identified their CDAD patients treated with intravenous metronidazole to assess the efficacy. IV metronidazole has a relatively large volume of distribution and properties that favor penetration into the inflamed colon. For inclusion in this study, CDAD must have been confirmed with ELISA testing and IV metronidazole must have been used as sole treatment for the initial 2 days. Ten patients, averaging 74 years of age, fulfilled entry criteria. All patients received 500 mg of intravenous metronidazole 3 times daily. Parenteral therapy was required because of vomiting or NG decompression in 8 patients and severe abdominal pain in 2 patients. Radiographic findings of ileus or colonic thickening were common. No patient developed toxic megacolon or required colectomy for refractory colitis. In this study, toxicity from IV met-
438
ronidazole was not seen (peripheral neuropathy is a known potential toxicity of prolonged therapy). One patient developed vomiting while on IV metronidazole, ultimately resolving when therapy could be changed to the oral route. Clinically important symptom parameters showed a trend toward improvement in the majority of patients. Two patients died because of underlying medical conditions. Both had been switched to oral metronidazole several days prior to their deaths. One patient died of sepsis, but with a confounding urinary tract infection and no autopsy, it could not be determined whether the death was caused by colitis or urosepsis. The authors report their experience as the largest case series of IV metronidazole for CDAD. They feel their article provides additional support of this therapy in patients incapable of taking enteral therapy. Ultimate proof of effectiveness would require a prospective, randomized study of IV versus oral metronidazole. FOLLOW UP: (Dr. J. P. Brooks) With the return of diarrheal stools on hospital day 2, another sample was sent for Clostridium difficile toxin testing and treatment was continued without alterations in plan. The second Clostridium difficile test was positive. The remainder of the fecal studies ultimately returned negative. The abdominal distention began to improve by the third day of admission. She was transferred out of the intensive care unit and bowel rest was discontinued. She was switched to oral metronidazole as she improved and tolerated a diet. Her bowel movements were formed by the time of discharge home on hospital day 6. On follow-up in the clinic 1 week later, she was completely asymptomatic.
CURRENT SURGERY • Volume 61/Number 5 • September/October 2004
Abdominal Distention and Diarrhea in a Young Female Maj J. Patrick Brooks, USAF, MC,*† Lt Col W. Brian Perry, USAF, MC,† and Melanie L. Richards, MD‡ *379th Air Expeditionary Wing/Expeditionary Medical Group, Al-Udeid Airbase, Qatar, †Wilford Hall Medical Center, San Antonio, Texas; and ‡The University of Texas Health Science Center at San Antonio, San Antonio, Texas PROBLEM: Marked abdominal distention and diarrhea. CLINICAL PRESENTATION: (Dr. J. P. Brooks) A 25year-old woman presented to the emergency department with complaints of abdominal distention, discomfort, and a 2-week history of worsening diarrhea. Her bowel movements ultimately became frequent and watery, but without blood. In the day prior to presentation, her bowel frequency diminished markedly and abdominal distention with discomfort developed. Her medical history was significant only for communityacquired pneumonia 1 month previously. She had no prior surgical procedures. Her only current medication was loperamide, prescribed by her general practitioner during a visit the previous day when her diarrhea was most severe. On further questioning, she recalled taking a brief course of antibiotics for her pneumonia. A computer record search confirmed a 4-day course of oral levofloxacin, 500 mg daily, filled 1 month previously; a chest x-ray at that time confirmed a right basilar pneumonia. Physical examination revealed a slender young female who appeared moderately ill, with a resting tachycardia to the 120s. Cardiovascular examination was unremarkable. The most striking finding was marked abdominal distention, tympany, and moderate, nonlocalized abdominal tenderness without guarding or signs of peritonitis. There were no palpable hernias; rectal examination revealed an empty vault without detectable blood. Laboratory studies were significant for a leukeocytosis (WBC 18,400). An acute abdominal series was notable for air-filled small bowel with air fluid levels and distended, air-filled colon with an ahaustral appearance (Fig. 1). The air terminated abruptly in the descending colon, compatible with colonic obstruction. Computed tomography (CT) was obtained with rectal and IV contrast to evaluate the possible obstruction. Again, Correspondence: Inquiries to Lt Col W. Brian Perry, USAF, MC, Wilford Hall Medical Center, 859 MSGS/MCSG, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236; fax: (210) 292-3893; e-mail: [email protected] The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the United States Government, the Department of Defense, or the Department of the Air Force.
CURRENT SURGERY • Published by Elsevier Inc. on behalf of the Association of Program Directors in Surgery
air-filled small and large bowels were seen with marked abdominal distention. The rectal contrast passed into the descending colon without evidence of obstruction (Fig. 2). There was marked thickening of the rectosigmoid colon. The surgical team was consulted. As obstruction was ruled out, this clinical picture of abdominal distention, thickened colon, and diarrhea represented a form of toxic colitis. Infectious colitis or inflammatory bowel disease were possibilities, but with the history of antibiotic use 1 month previously, toxic Clostridium difficile colitis was favored. The patient was then admitted to the intensive care unit with contact precautions. A nasogastric tube and foley catheter were inserted, and intravenous metronidazole and fluid resuscitation, initiated in the emergency department, was continued. She had not had any further bowel movements since presentation, so toxin assays for Clostridium difficile could not be performed until the next day. Therefore, the patient underwent flexible sigmoidoscopy to confirm the diagnosis that evening in the intensive care unit. Minimal insufflation was used. The rectosigmoid colon was found to be distended and coated in densely adherent, yellow-green mucous (Fig. 3). Copious irrigation was able to reveal inflamed mucosa beneath the pseudomembrane. A fluid sample for fecal leukocytes, culture for fecal pathogens, ova and parasites, and Clostridium difficile toxin was collected. No biopsies were taken. The patient tolerated the limited examination well. With these pathognomonic findings, intravenous metronidazole was continued as severe ileus would likely limit enteric absorption of medications. As a result of her toxic colitis, enteric vancomycin was also administered, via the nasogastric tube. By the next day, the patient had made no improvement in her distention. The fecal leukocyte count was 20, and the Clostridium difficile toxin assay was negative. She was hemodynamically stable with good urine output and no signs of peritonitis. GROUP DISCUSSION: (Dr. W. B. Perry and faculty) This patient with toxic colitis has the potential to become ill and require urgent colectomy. Intensive care unit admission, fluid rescuscitation, bowel rest, and a search for a confirmatory diagnosis are all warranted. Clostridium difficile colitis was fa0149-7944/04/$30.00 doi:10.1016/j.cursur.2004.05.018
435
1. Clostridium difficile-associated diarhea and colitis (Review) Yassin SF, Young-Fadok TM, Zein NN, Pardi DS. Mayo Clin Proc. 2001;76:725-730.
FIGURE 1. Plain abdominal radiograph shows distended small and large bowel.
vored at presentation, and the early use of gentle sigmoidoscopy allowed for early confirmation of that diagnosis. Endoscopic findings consistent with inflammatory bowel disease without a history of antibiotic use would prompt treatment with intravenous steroids and continued close observation. Alternatively, if stool cultures ultimately revealed an infectious colitis other than Clostridium difficile, appropriate therapy could be initiated. In this patient with pseudomembranes on endoscopy, the initial negative Clostridium difficile assay would not change my management. Assuming no worsening condition, peritonitis, or organ system failure, which would prompt operative intervention, I would continue with medical management and submit additional fecal samples for Clostridium difficile toxin testing. LITERATURE UPDATE WITH COMMENTARY: (Dr. J. P. Brooks) Clostridium difficile colitis has been increasing in recent years along with the increasing use of antibiotics. Although most cases are readily treated with cessation of the offending antibiotic and initiation of oral metronidazole, toxic colitis from Clostridium difficile represents the severe end of the spectrum with the potential for perforation, peritonitis, and death. When surgical therapy is required, mortality is still fairly high. We will begin the literature review with an excellent review article from the Mayo Clinic. 436
The incidence of Clostridium difficile colitis is increasing. Although the disease was described before the antibiotic era, Clostridium difficile-associated diarrhea (CDAD) typically occurs after exposure to antibiotics. The most frequent indication for antibiotic use is perioperative prophylaxis, and therefore, surgical patients make up more than half of all patients with CDAD. Any antimicrobial agent can incite the disease, including vancomycin and metronidazole. Clindamycin, lincomycin, ampicillin, or the cephalosporins are involved in the majority of cases. Fluoroquinolones are less likely to cause the disease. Clostridium difficile is present in an asymptomatic carriage stage in 50% of children, but colitis is rare in infants and children possibly because of a higher prevalence of antibodies or immature toxin receptors. Clostridium difficile carriage is uncommon in healthy adults (3% or less), but because it can occur after a single dose of antibiotics, the prevalence in antibiotictreated inpatients is up to 25%. Up to 39% of patients treated with antibiotics will develop some form of antibiotic-associated diarrhea, but Clostridium difficile colitis will be the cause of the diarrhea in only 10% of these patients. Treatment with antimicrobials can alter the balance of normal gut flora and allow overgrowth of Clostridium difficile. The bacteria are noninvasive, so development of colitis is dependent on their ability to produce toxins. Toxin A causes cytotoxicity by disrupting cytoplasmic microfilaments. Toxin B can then enter the cell and cause further toxicity. The damage can range from minimal inflammation of the mucosa to toxic dilation or perforation from inflammation in deeper layers. Clostridium difficile-associated diarrhea usually develops within 2 weeks after initiation of the causative antibiotic, but it can occur at any time within 6 weeks. Profuse, watery diarrhea
FIGURE 2. Abdominal CT scan shows intestinal dilitation without mechanical obstruction.
CURRENT SURGERY • Volume 61/Number 5 • September/October 2004
FIGURE 3. Endoscopic appearance of pseudomembranes.
develops that occasionally contains mucous or blood. The symptoms may be limited to loose stools or progress to abdominal distention, toxic megacolon, sepsis, peritonitis, and multisystem organ failure. Overall mortality is low at 2% to 5%, but with toxic megacolon, mortality ranges from 30% to 80%. Delay in diagnosis of CDAD is associated with higher mortality. Diagnosis of CDAD begins with recognizing the clinical findings as described above, but the disease may occur as an unexplained leukocytosis in an asymptomatic hospitalized patient. The fecal leukocyte count may be elevated. In the appropriate situation, treatment may be initiated prior to confirmatory studies, but typically Clostridium difficile testing will be in order. The enzyme-linked immunosorbent assay (ELISA) for detection of toxin A or B in the stool is preferred at many institutions. Culture for Clostridium difficile is difficult and not specific for active disease. Stool cytotoxicity is considered the gold standard but is expensive and time consuming. To make up for the lower sensitivity of ELISA, up to 3 stool specimens should be tested to increase the sensitivity from 75% to 90%. Endoscopy is beneficial when a quick diagnosis is needed. Although it can be normal in mild disease, patients with more significant CDAD will have erythematous mucosa, progressing to ulcerations and ultimately coalescing exudates of yellowish pseudomembranes. Colonoscopy may be required on occasion when the disease is limited to the proximal colon, beyond the reach of the flexible sigmoidoscope. In patients with severe disease, endoscopy should only be performed by experienced physicians with minimal air insufflation. Treatment begins with supportive therapy, isolation, and discontinuation of the offending antibiotic whenever possible. Neither antidiarrheals nor narcotics should be used, as they may precipitate severe colitis. Metronidazole should be added when therapy is required for significant symptoms or failure of supportive therapy alone. Oral therapy is felt to be superior to the intravenous route. Oral vancomycin is reserved for children,
failure of metronidazole, or severely ill patients. Although metronidazole has comparable efficacy with vancomycin, some Clostridium difficile strains are metronidazole-resistant and vancomycin response rates have been reported at up to 100%. When parenteral therapy is required as a result of ileus, intravenous metronidazole is required, and enteric vancomycin may be added via nasogastric tube or enema if desired. Recurrence of CDAD occurs in 10% to 30% of patients, and it usually responds to metronidazole. With continuing recurrences, prolonged courses of vancomycin may be used. Another option is pulse therapy—alternating treatment for 5 to 7 days of antibiotics with 5- to 7-day periods without antibiotics. Surgical treatment of CDAD is required in 5% or less and can have a high mortality. Total abdominal colectomy with end ileostomy is the procedure of choice. The surgical treatment of this disease is discussed in the following article. 2. Timing of surgery for fulminating pseudomembranous colitis Synnott K, Mealy K, Merry C, Kyne L, Keane C, Quill R. Br J Surg. 1998;85:229-231. At the time of publication of this article, per their review, there had been less than 50 reported cases of fulminant clostridial colitis requiring colectomy, with a collective mortality of 35%. The authors reviewed their experience during an outbreak of CDAD in St. James’s Hospital, Dublin, Ireland. Toxin assays were positive in 138 patients during a 6-month period. Nine of these patients died, 4 of 5 whom required surgery versus 5 of 133 requiring only medical treatment. Indications for surgical treatment of CDAD were (1) peritonitis, (2) shock, (3) multisystem organ failure, and (4) progression of disease despite maximal Clostridium difficile antibiotic therapy. Two of the surgical patients were relapses from prior treatment. Three patients had flexible sigmoidoscopy showing characteristic pseudomembranes. Subtotal abdominal colectomy with end ileostomy was performed in all 5 surgical patients. In 3 patients, a distal mucous fistula was used to allow irrigation of the rectal stump with antibiotics. Operative findings invariably included ascites, a markedly distended and edematous colon without serosal inflammation, and severe mucosal ulceration of the opened specimen. Postoperative death occurred as a result of persistant respiratory failure, myocardial infarction, and in 2 patients as a result of progressive multisystem organ failure. The last surgical patient recovered fully and was the only survivor and the youngest of the group. It was felt that the advanced age of these patients (average 69 years) and accompanying comorbidities contributed to the unusually high mortality. The authors also suggest that improved awareness of the potentially fatal nature of the disease late in the outbreak period may have contributed to early consultation and survival in the fifth operative patient. Based on their experience, they recommend joint medical and
CURRENT SURGERY • Volume 61/Number 5 • September/October 2004
437
surgical management for fulminating Clostridium difficile colitis and favor earlier operative intervention before organ failure develops. The following paper addresses the issue of intravenous metronidazole for CDAD. 3. Intravenous metronidazole for the treatment of clostridium difficile colitis Friedenberg F, Fernandez A, Kaul V, Niami PR, Levine GM. Dis Colon Rectum. 2001;44:11761180. Oral therapy for CDAD with metronidazole or vancomycin is the favored route for treatment, but occasionally nausea, vomiting, or ileus precludes the enteric route. Intravenous metronidazole has been reported as an alternative treatment in case series, but there is a lack of rigorous data. The authors of this article therefore retrospectively identified their CDAD patients treated with intravenous metronidazole to assess the efficacy. IV metronidazole has a relatively large volume of distribution and properties that favor penetration into the inflamed colon. For inclusion in this study, CDAD must have been confirmed with ELISA testing and IV metronidazole must have been used as sole treatment for the initial 2 days. Ten patients, averaging 74 years of age, fulfilled entry criteria. All patients received 500 mg of intravenous metronidazole 3 times daily. Parenteral therapy was required because of vomiting or NG decompression in 8 patients and severe abdominal pain in 2 patients. Radiographic findings of ileus or colonic thickening were common. No patient developed toxic megacolon or required colectomy for refractory colitis. In this study, toxicity from IV met-
438
ronidazole was not seen (peripheral neuropathy is a known potential toxicity of prolonged therapy). One patient developed vomiting while on IV metronidazole, ultimately resolving when therapy could be changed to the oral route. Clinically important symptom parameters showed a trend toward improvement in the majority of patients. Two patients died because of underlying medical conditions. Both had been switched to oral metronidazole several days prior to their deaths. One patient died of sepsis, but with a confounding urinary tract infection and no autopsy, it could not be determined whether the death was caused by colitis or urosepsis. The authors report their experience as the largest case series of IV metronidazole for CDAD. They feel their article provides additional support of this therapy in patients incapable of taking enteral therapy. Ultimate proof of effectiveness would require a prospective, randomized study of IV versus oral metronidazole. FOLLOW UP: (Dr. J. P. Brooks) With the return of diarrheal stools on hospital day 2, another sample was sent for Clostridium difficile toxin testing and treatment was continued without alterations in plan. The second Clostridium difficile test was positive. The remainder of the fecal studies ultimately returned negative. The abdominal distention began to improve by the third day of admission. She was transferred out of the intensive care unit and bowel rest was discontinued. She was switched to oral metronidazole as she improved and tolerated a diet. Her bowel movements were formed by the time of discharge home on hospital day 6. On follow-up in the clinic 1 week later, she was completely asymptomatic.
CURRENT SURGERY • Volume 61/Number 5 • September/October 2004