Pseudomonas aeruginosa as a cause of infectious diarrhea successfully treated with oral ciprofloxacin

OBJECTIVE: To describe an immunocompromised patient (without AIDS) with nosocomial infectious diarrhea caused by Pseudomonas aeruginosa. Oral ciprofloxacin therapy proved to be effective. CASE SUMMARY: An 80-year-old woman with type II diabetes mellitus and hypertension developed progressive renal insufficiency, was hospitalized because of uremia, and underwent hemodialysis. When the patient developed hematochezia, Duke's C sigmoid colon cancer was detected and successfully resected. She received broad-spectrum antibiotics in the perioperative period. The patient then developed profuse diarrhea associated with abdominal cramping, a low-grade fever, prostration, and headache. The patient then started to received vancomycin 500 mg po qid empirically. Four days later, the diarrhea continued unabated, the Clostridium difficile titer was negative, and the vancomycin therapy was stopped. However, the stool culture was positive for heavy growth of P. aeruginosa sensitive to ciprofloxacin. The patient then began to receive ciprofloxacin 500 mg po bid. Within 3 days the diarrhea stopped. Oral ciprofloxacin therapy was continued for 10 days and the patient remained free of symptoms with formed stools thereafter. DISCUSSION: Diarrhea following the use of broad-spectrum antibiotics implicates pseudomembranous colitis as the cause. The patient did not respond to oral vancomycin therapy and had a negative stool assay for C. difficile toxin. This patient was believed to have Pseudomonas enteritis, which was confirmed by 2 positive stool cultures. The administration of oral ciprofloxacin therapy stopped her diarrhea with a rapid resolution of symptoms. CONCLUSIONS: P. aeruginosa as a cause of infectious diarrhea is unusual. When it occurs, it usually represents a nosocomial infection in an immunocompromised host. This report illustrates that oral ciprofloxacin therapy is effective for Pseudomonas enteritis, with rapid resolution of symptoms.     

Clostridium difficile colitis: factors influencing treatment failure and relapse--a prospective evaluation

OBJECTIVE: The aim of this study was to identify patient related factors that may influence the treatment response and relapse following Clostridium difficile (C. difficile) colitis. METHODS: A total of 36 patients with C. difficile colitis were followed for 3 months. Age, sex, place of residence, severity of infection, treatment, underlying medical condition, and treatment were compared in patients who failed to respond to treatment in 14 days and in patients who relapsed after a successful treatment. Student's t test and Fisher's exact test were used to compare the groups. A p value of <0.05 was considered significant. RESULTS: A low serum albumin (p=0.016) and continuation of systemic antibiotic treatment were found to be associated with refractoriness to treatment. Continuation or restarting of antibiotics after successful treatment increases the risk of relapse (p=0.003). The age, sex place of residence, underlying medical condition, and type of precipitating antibiotics had no effect on the treatment response and relapse. The severity of colitis and the type of therapy (metronidazole vs vancomycin) did not influence the treatment response or relapse. CONCLUSION: Low serum albumin serves as a useful marker for patients who require prolonged treatment for C. difficile colitis. It is prudent to review the need for the continuation of systemic antibiotic treatment, as it adversely affects the treatment response and increases the risk of relapse.     

Clostridium difficile-associated diarrhea and colitis: clinical manifestations, diagnosis, and treatment

PURPOSE: This review examines the pathogenesis, clinical manifestations, diagnosis, and current medical and operative strategies in the treatment of Clostridium difficile diarrhea and colitis. Prevention and future avenues of research are also investigated. METHODS: A review of the literature was conducted with the use of MEDLINE. RESULTS: C. difficile is a gram-positive, spore-forming bacterium capable of causing toxigenic colitis in susceptible patients, usually those receiving antibiotics. Overgrowth of toxigenic strains may result in a spectrum of disease, including becoming an asymptomatic carrier, diarrhea, self-limited colitis, fulminant colitis, and toxic megacolon. Diagnosis requires a high index of suspicion and depends on clinical data, laboratory stool studies (enzyme-linked immunoabsorbent assay and cytotoxin test), and endoscopy in selected cases. Protocols for treatment of primary and relapsing infections are provided in algorithm format. Discontinuation of antibiotics may be enough to resolve symptoms. Medical management with oral metronidazole or vancomycin is the first-line therapy for those with symptomatic colitis. Teicoplanin, Saccharomyces spp. and Lactobacillus spp., and intravenous IgG antitoxin are reserved for more recalcitrant cases. Refractory or relapsing infections may require vancomycin given orally or other newer modalities. Fulminant colitis and toxic megacolon warrant subtotal colectomy. Cost, in terms of extended hospital stay, medical and surgical management, and, in some cases, ward closure, is thought to be formidable. Review of perioperative antibiotic policies and analysis of hospital formularies may contribute to prevention and decreased costs. CONCLUSION: C. difficile diarrhea and colitis is a nosocomial infection that may result in significant morbidity, mortality, and medical costs. Standard laboratory studies and endoscopic evaluation assist in the diagnosis of clinically suspicious cases. Appropriate perioperative antibiotic dosing, narrowing the antibiotic spectrum when treating infections, and discontinuing antibiotics at appropriate intervals prevent toxic sequelae.     

Review article: antibiotic-induced Clostridium difficile infection

The great majority of cases of Clostridium difficile infection are hospital-acquired, and the reported incidence in England and Wales has increased sixfold between 1990 and 1993, with at least 17 patients dying in a recent large nosocomial outbreak. C. difficile infection accounts for an average 3-week increased length of stay in hospital. Acquisition of a toxigenic strain of Clostridium difficile may be followed by asymptomatic carriage, diarrhoea, colitis or pseudomembranous colitis. Antibiotic treatment and older age are major risk factors for the development of symptomatic disease, but less well-defined differences in strain virulence and host susceptibility are also probably important. Accurate data on the relative risks of different antibiotics to induce symptomatic C. difficile infection are scarce, but third-generation cephalosporins are frequently implicated. New kits are becoming available for the laboratory diagnosis of C. difficile infection but many of these lack sensitivity. Oral metronidazole or vancomycin are the main treatment options but avoidance of further antibiotics should also be encouraged where possible. The role of environmental C. difficile spores, which are highly resistant to conventional disinfectants, needs to be defined. Proven strategies for the prevention of C. difficile infection are required, in particular protocols to ensure that cross-infection does not occur.     

Clostridium difficile infections. Current aspects

Clostridium difficile is a gram-positive anaerobe that forms subterminal spores. It is now one of major nosocomial pathogens, mainly in older patients, because of its ability to persist in the environment and to become established in the gastrointestinal tract once the natural microflora has been modified by antibiotic therapy. Toxigenic strains of C. difficile produce toxin A (enterotoxin) or toxin B (cytotoxin) or both with cause the cytotoxic effect "rounding". C. difficile can spread from patient to patient and, probably, the primary way by which the organism is spread is by health care workers. C. difficile causes intestinal diseases ranging by mild diarrhea (antibiotic associated diarrhea) to fatal pseudomembranous colitis (PMC). The current therapy is based on oral administration of metronidazole or vancomycin . In patients non responders or that continue to relapse can be used other forms of therapy: antibiotic (teicoplanine, bacitracine, rifamixine); anion exchange resin (colestipol, colestiramine); probiotic therapy (S. boulardii, lactobacilli and fecal enemas). New and improved studies will lead to new and better ways of treating patients and better understanding of this unusual pathogen and how it causes diseases.     

Colitis associated to chemotherapy with 5-fluorouracil

Antitumoral agents, especially when administered in combination, can induce pseudomembranous colitis, due to their antimitotic and antibacterial properties. Although patients given 5-fluorouracil frequently show nonspecific colitis or diarrhea without colitis, very few cases of proven pseudomembranous colitis have been described during 5-fluorouracil monotherapy. We describe the second case reported in the English literature of a typical pseudomembranous colitis occurring in a patient given 5-fluorouracil as a single antimitotic agent for colonic cancer. Intestinal injury was not preceded by antibiotic therapy. Although both stool and pseudomembrane culture did not yield C. difficile, oral vancomycin was started. This treatment led to a prompt improvement of intestinal symptoms and colitis was resolved in one week.     

Antibodies to recombinant Clostridium difficile toxins A and B are an effective treatment and prevent relapse of C. difficile-associated disease in a hamster model of infection

Clostridium difficile causes antibiotic-associated diarrhea and colitis in humans through the actions of toxin A and toxin B on the colonic mucosa. At present, broad-spectrum antibiotic drugs are used to treat this disease, and patients suffer from high relapse rates after termination of treatment. This study examined the role of both toxins in pathogenesis and the ability of orally administered avian antibodies against recombinant epitopes of toxin A and toxin B to treat C. difficile-associated disease (CDAD). DNA fragments representing the entire gene of each toxin were cloned, expressed, and affinity purified. Hens were immunized with these purified recombinant-protein fragments of toxin A and toxin B. Toxin-neutralizing antibodies fractionated from egg yolks were evaluated by a toxin neutralization assay in Syrian hamsters. The carboxy-terminal region of each toxin was most effective in generating toxin-neutralizing antibodies. With a hamster infection model, antibodies to both toxins A and B (CDAD antitoxin) were required to prevent morbidity and mortality from infection. In contrast to vancomycin, CDAD antitoxin prevented relapse and subsequent C. difficile reinfection in the hamsters. These results indicate that CDAD antitoxin may be effective in the treatment and management of CDAD in humans.     

Atypical presentation of Clostridium difficile colitis in patients with cystic fibrosis

OBJECTIVE: This report describes the unusual presentation of Clostridium difficile colitis in five patients with cystic fibrosis and the role of CT in first suggesting the correct diagnosis in this group of patients. Because of the absence of watery diarrhea and the presence of abdominal bloating and decreased stooling, cystic fibrosis patients with C. difficile colitis will be treated for stool impaction, meconium ileus equivalent, or distal intestinal obstruction syndrome. CT of the abdomen, performed in these five patients because of their lack of improvement after standard therapy for stool impaction, showed an extensive pancolitis later confirmed to be caused by C. difficile infection. CONCLUSION: In patients with cystic fibrosis, imaging findings of a pancolitis should raise the possibility of C. difficile colitis despite the lack of watery diarrhea. Anticlostridial treatment can be initiated before bacteriologic confirmation is obtained.     

Some aspects of the Clostridium difficile infection

Clostridium difficile is now regarded as the most common nosocomial enteric pathogen. C. difficile infection has a wide spectrum of a clinical presentation ranging from asymptomatic carriage to the fulminant colitis. Antibiotic therapy is the most important risk factor in pathogen contagion, however other factors are also involved. Typical pathophysiology: 1. alteration of the indigenous colonic flora by antibodies, 2. ingestion of spores, 3. colonization by Clostridium difficile, 4. production of its toxins. Both entherotoxin A and cytotoxin B are active in human colon. The mode of action of these toxins is already quite well known. The main treatment includes withdrawal of the inducing agents, supported occasionally by oral Vancomycin and Metronidazole. Relapse is a major complication.     

Clostridium difficile colitis associated with treatment of Helicobacter pylori infection

Helicobacter pylori infection of the stomach is being detected and treated more often now than ever before. This is likely to result in an increase in complications such as antibiotic-associated diarrhea. However, there is no literature on the incidence of such diarrhea, particularly Clostridium difficile colitis, in patients treated for Helicobacter pylori infection. We report the case of a patient who developed Clostridium difficile colitis after treatment for Helicobacter pylori infection with metronidazole, amoxicillin, H2 blockers, and bismuth subsalicylate. This patient presented with severe diarrhea that responded to a course of metronidazole with rapid disappearance of symptoms. The incidence of Clostridium difficile colitis in patients treated for Helicobacter pylori infection has not been studied. This unique association, although not unexpected, has not yet been reported in the literature. The increasing number of patients being diagnosed and treated for this infection requires a heightened awareness on the part of physicians, to assure early diagnosis and treatment of this treatable, yet potentially dangerous, complication.     

Critical enhancement of the in-medium nucleon-nucleon cross section at low temperatures

As part of an 18-month carcinogenicity study, 680 Syrian hamsters (Mesocricetus auratus) received daily gavage doses of fenazaquin, an experimental miticide. Mortality associated with severe enteritis was noticed beginning when the hamsters were 4 months old and ranged from one to five deaths per month until the hamsters were about 10 months old, when 41 deaths occurred in a 1-month period. Ante- and postmortem findings were consistent with those reported for antibiotic-induced enteritis in hamsters. Clostridium difficile was isolated from 12 of the 13 samples of cecal contents analyzed. Toxin assays of C. difficile isolates collected from 11 affected animals were positive for both cyto- and enterotoxins. Daily oral administration of vancomycin hydrochloride at a dose of 20 mg/kg was initiated when the hamsters were about 10 months old. Deaths due to C. difficile enteritis were significantly decreased within 2 weeks, and treatment was continued for 3 months. A trial withdrawal period for a subset of 64 hamsters (approximately 16% of the total population) was initiated to evaluate survival after discontinuation of the antibiotic treatment. Clostridium difficile enteritis recurred within 2 weeks and caused 19 deaths during the next month; therefore, these hamsters were returned to daily vancomycin treatment for the remainder of the study. With the exception of severe gaseous distention of the ceca, which caused death in 17 (< 4% of the total population) of the affected hamsters, vancomycin treatment did not cause any major adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nasopharyngeal perforation: an exceptional accident during digestive endoscopy]

We describe a case of systemic cytomegalovirus (CMV) infection in an ulcerative colitis patient admitted to the hospital for an acute flare-up of his colitis. He was treated with combination immunosuppressive therapy including i.v. cyclosporine and corticosteroids and PO azathioprine. Severe bilateral stabbing knee pain was the only manifestation of CMV disease, which quickly responded to adequate antiviral therapy.     

Ventilator-induced injury: from barotrauma to biotrauma

In Sweden, mares sometimes develop acute, often fatal, colitis when their foals are treated orally with erythromycin and rifampicin for Rhodococcus (R.) equi infection. Clostridium (C.) difficile, or its cytotoxin, was demonstrated in faecal samples from 5 of 11 (45%) mares with diarrhoea. By contrast C. difficile was not found in the faecal flora of 12 healthy mares with foals treated for R. equi infection or in 56 healthy mares with healthy untreated foals. No other enteric pathogen was isolated from any diarrhoeic mare. Of 7 investigated treated foals, 4 had a high (1651.0, 1468.3, 273.0 and 88.8 microg/g) faecal concentration of erythromycin. The dams of those 4 foals developed acute colitis, whereas the dams of 3 foals with a lower (26.3, 4.6 and 3.7 microg/g) faecal erythromycin concentration remained healthy, indicating that there might have been an accidental intake of erythromycin by mares. The foals treated with antibiotics were regarded as asymptomatic carriers and potential reservoirs, as C. difficile was found in 7 of 16 foals investigated, while 56 untreated foals proved negative. The isolated C. difficile strains proved resistant to both erythromycin (MIC>256 mg/l) and rifampicin (MIC>32 mg/l), a fact that may have favoured the growth of C. difficile in the foal intestine. All mares found positive for C. difficile were, or had recently been, hospitalised together with their foals, indicating that C. difficile may be a nosocomial infection, in horses. The results emphasise that routine testing for C. difficile and its cytotoxin is recommended when acute colitis occurs in mares when their foals are treated with erythromycin and rifampicin. Preventive measures in order to avoid accidental ingestion of erythromycin by mares from the treatment of their foals are suggested.     

Review article: treatment of Clostridium difficile infection

AIM: A systematic review of controlled trials of therapy of Clostridium difficile intestinal infection using methodology described by the Cochrane Collaboration. METHODS: Trials were identified by searching computer databases over the years 1978-1996. Trials were included if they were (a) prospective randomized, controlled trials and (b) included patients with symptomatic disease. The primary end-point was clinical resolution of diarrhoea. Secondary end-points were clinical relapse and stool clearance of C. difficile and C. difficile toxin. RESULTS: Nine trials (469 patients) satisfying the inclusion criteria were identified. Two trials were placebo controlled. Six trials compared vancomycin to other antibiotics (fusidic acid, bacitracin, teicoplanin and metronidazole). For clinical resolution response rates ranged from 21 (placebo) to 100% (vancomycin). On pooling the trials, no antibiotic showed clear therapeutic superiority. Rates of clinical relapse ranged from 5 to 42%. Only one trial showed significant advantage of one antibiotic over another for prevention of relapse (teicoplanin vs. fusidic acid). CONCLUSION: The published data are limited, and further studies are required.     

Lipid metabolism in pregnancy. VIII. Effects of dietary fat versus carbohydrate on lipoprotein and hepatic lipids and tissue triglyceride lipases

From 1324 patients with antibiotic-associated diarrhea (AAD) 1643 stool samples were analyzed by a cell test for Clostridium difficile toxin in stool filtrates and cultivation for occurrence of C. difficile strains. In patients with no detectable toxin in their stool strains of C. difficile were isolated in 2.2% whereas when toxin was detectable, the isolation rate varied from 17% to 36%. Furthermore, there was a correlation between toxin titre in stool filtrate and production of cytotoxin in vitro by the corresponding C. difficile strains. Five clostridial strains, not belonging to the species C. difficile, were found to produce typical cytotoxin in vitro. However, five strains identified as C. difficile by biochemical reactions and gas liquid chromatography, did not produce an extracellular cytotoxin. The antibiotic susceptibility patterns of the Clostridium strains were investigated. No correlation was recognized between antibiotic resistance of isolated Clostridium strains and the AAD-inducing antibiotic penicillins and linco/clindamycin. Neither did cases of relapse of diarrheal disease after vancomycin treatment harbour C. difficile strains with increased resistance to vancomycin. It is concluded that the pathogenesis of antibiotic-associated enterocolitis is more complex than a mere intestinal overgrowth of resistant strains of C. difficile.     

Association of Clostridium difficile with enterocolitis and lactose intolerance in a foal

Diagnoses of Clostridium difficile enterocolitis and lactose intolerance were made in a neonatal foal with persistent diarrhea. It was determined that the foal had lactose intolerance on the basis of the results of a lactose tolerance test, and a diagnosis of C difficile enterocolitis was subsequently made. The foal responded to oral administration of metronidazole and lactase. Lactose intolerance is a secondary problem most commonly associated with rotavirus infection, but it can be caused by any condition affecting the small intestine. Because C difficile can affect the small intestine in foals, it was presumably the cause of the lactose intolerance in this foal with persistent diarrhea. Oral administration of lactase was not initially successful in this foal, most likely because of ongoing C difficile enterocolitis. Presumably, metronidazole was an effective treatment for C difficile enterocolitis and administration of lactase allowed for normal digestion of milk until endogenous lactose production returned. Clostridium difficile enterocolitis and lactose intolerance should be considered as differential diagnoses in neonatal foals with diarrhea, especially when the foal is bright and alert.     

Severe Clostridium difficile-associated colitis in young patients with cystic fibrosis

We report four patients with cystic fibrosis and fulminant Clostridium difficile-associated colitis: two died, and one required hemicolectomy. Three of four patients carried the N1303K mutation. Severe and fatal C. difficile colitis can occur in cystic fibrosis patients, possibly with a genotype-specific predilection (i.e., N1303K/other). Because cystic fibrosis patients may have a wide spectrum of gastrointestinal symptoms, disease caused by C. difficile must be considered when these patients have acute abdominal pain, diarrhea, or severe leukocytosis.     

Drug-associated hemorrhagic enteritis

Drug-associated hemorrhagic colitis are divided into antibiotic associated hemorrhagic colitis (AAHC) and other drug associated hemorrhagic colitis. AAHC are mainly caused by oral usage of Ampicillin and its derivatives (85%). Initially AAHC are believed to be caused by Klebsiella oxytoca overgrowth. However, these organisum has no exotoxin like Clostridium difficile and pathogenesis of AAHC are still unresolved. Typical AAHC are diagnosed by colonoscopy with diffuse hemorrhage and edema mainly found in descending colon and transverse colon. NSAIDs are also the cause of hemorrhagic colitis like AAHC. Mephenamic acid are famous for this complication. Diarrhea is one of the main complication of oral 5-fluorouracil administration and even causes hemorrhagic colitis. Its histology are characteristic in gland atrophy. Gold colitis are reported 36 cases in rheumatoid arthritis patients. Exact mechanism of bleeding are not understood. NSAIDs may cause collagenous colitis and or lymphocytic colitis in RA patients. Other rare hemorrhagic colitis are associated with azathioprine, methyl dopa, interferon alfa etc. NSAIDs and anticoagulants are well known drugs for complication of GI bleeding making hemorrhagic enteritis.     

Clostridium difficile and older adults: what primary care providers should know

Clostridium difficile poses particular risk for older adults, who are subject to more serious symptoms than younger patients. Antibiotic exposure and other risk factors are associated with the pathogenesis of C. difficile-associated disease. Treatment goals include prescribing anti-C. difficile activity agents (when indicated), attending to volume status and prescribing oral rehydration therapy as needed, avoiding the use of antiperistaltic drugs, discontinuing any offending antibiotics, avoiding the indiscriminate use of broad-spectrum antibiotics, providing supportive therapy, following infection control protocols, and eliminating environmental contaminants.     

Antibacterial activity of teicoplanin against Clostridium difficile

The in vitro inhibitory action of teicoplanin, vancomycin, metronidazole and clindamycin against clinical isolates of Clostridium difficile was investigated. Minimum inhibitory concentrations (MICs) were determined using E test. Teicoplanin (MIC range 0.023-0.75 microgram/ml), vancomycin (MIC range 0.5-3 micrograms/ml) and metronidazole (MIC range 0.19-1 microgram/ml) were all very active against the isolates examined. No resistant strains of C. difficile to those three antimicrobial agents were observed, whereas resistance to clindamycin was found in 39.5% of the tested strains. Teicoplanin was about 4-times more potent than vancomycin. It appears to be a more promising antimicrobial for treatment of C. difficile enteric disease.