Saturday, September 30, 2006

Antibiotic-Associated Colitis

Antibiotic-Associated Colitis

Antibiotic-associated colitis is inflammation of the large intestine caused by the growth of unusual bacteria that results from the use of antibiotics.

Many antibiotics alter the balance among the types and quantity of bacteria in the intestine, thus allowing certain disease-causing bacteria to multiply and replace other bacteria. The type of bacteria that most commonly overgrows and causes infection is Clostridium difficile. Clostridium difficile infection releases two toxins that can damage the protective lining of the large intestine.

Almost any antibiotic can cause this disorder, but clindamycinSome Trade Names CLEOCIN, penicillins such as ampicillinSome Trade Names OMNIPENPOLYCILLINPRINCIPEN, and cephalosporins such as cephalexinSome Trade Names KEFLEXare implicated most often. Other commonly involved antibiotics include erythromycinSome Trade Names E-MYCINERYTHROCINILOSONE, sulfonamides such as sulfamethoxazoleSome Trade Names GANTANOL, chloramphenicolSome Trade Names CHLOROMYCETIN, tetracyclineSome Trade Names ACHROMYCIN VTETRACYNSUMYCIN, and quinolones such as norfloxacinSome Trade Names NOROXIN.

Clostridium difficile infection is most common when an antibiotic is taken by mouth, but it also occurs when antibiotics are injected or administered intravenously. The risk of developing antibiotic-associated colitis increases with age.


Symptoms usually begin while the person is taking antibiotics. However, in one third of people who have this disorder, symptoms do not appear until 1 to 10 days after treatment has stopped, and in some people, symptoms do not appear for as long as 6 weeks afterward.

Symptoms vary according to the degree of inflammation caused by the bacteria, ranging from slightly loose stools to bloody diarrhea, abdominal pain, and fever. The most severe cases may involve life-threatening dehydration, low blood pressure, toxic megacolon (see Inflammatory Bowel Diseases: Complications), and perforation of the large intestine


The diagnosis of antibiotic-associated colitis is confirmed when one of the toxins produced by Clostridium difficile is identified in a stool sample. A toxin is found in about 20% of people with mild antibiotic-associated colitis and in more than 90% of those with severe antibiotic-associated colitis. Sometimes two or three stool samples must be obtained before the toxin is detected.

A doctor can also diagnose antibiotic-associated colitis by inspecting the lower part of the inflamed large intestine (the sigmoid colon), usually through a sigmoidoscope (a rigid or flexible viewing tube). A colonoscope (a longer flexible viewing tube) is used to examine the entire large intestine if the diseased section of intestine is higher than the reach of the sigmoidoscope. These procedures, however, usually are not required.


If a person with antibiotic-associated colitis has diarrhea while taking antibiotics, the drugs are discontinued immediately unless they are essential. Drugs that slow the movement of the intestine, such as diphenoxylate, generally are avoided because they may prolong the disorder by keeping the disease-causing toxin in contact with the large intestine. Antibiotic-induced diarrhea without complications usually subsides on its own within 10 to 12 days after the antibiotic has been stopped. When it does, no other therapy is required. However, if mild symptoms persist, cholestyramineSome Trade Names QUESTRANmay be effective, probably because it binds itself to the toxin.

For most cases of more severe antibiotic-associated colitis, the antibiotic metronidazoleSome Trade Names FLAGYLis effective against Clostridium difficile. The antibiotic vancomycinSome Trade Names VANCOCINis reserved for the most severe or resistant cases. Symptoms return in up to 20% of people with this disorder, and treatment with antibiotics is repeated. If diarrhea returns repeatedly, prolonged antibiotic therapy may be needed. Some people are treated with preparations of lactobacillus given by mouth or bacteroides given rectally to restock the intestine with normal bacteria; however, these treatments are not used routinely.

Rarely, antibiotic-associated colitis is so severe that the person must be hospitalized to receive intravenous fluids, electrolytes (such as sodium, magnesium, calcium, and potassium), and blood transfusions. A temporary ileostomy (a surgically created connection between the small intestine and an opening in the abdominal wall that diverts stool from the large intestine and rectum) or surgical removal of the large intestine occasionally is needed in these severe cases as a lifesaving measure.


Friday, September 22, 2006

Prophylactic antibiotic use in open fractures: an evidence-based guideline.

Prophylactic antibiotic use in open fractures: an evidence-based guideline.

Surg Infect (Larchmt). 2006 Aug;7(4):379-405

Department of Surgery, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey.


Prolonged courses of broad-spectrum antibiotics are often cited as the standard of care for prevention of infective complications of open fractures. The origins of these recommendations are obscure, however, and multi-drug-resistant systemic infections attributable to antibiotic overuse are common life-threatening problems in current intensive care unit practice.


To review systematically the effects of prophylactic antibiotic administration on the incidence of infections complicating open fractures.

Data Sources:

Computerized bibliographic search of published research and citation review of relevant articles.

Study Selection:

All published clinical trials claiming to evaluate, or cited elsewhere as being authoritative regarding, the role of antibiotics in open fracture management were identified and then evaluated according to published guidelines for evidence-based medicine. Only small studies (<20>

Data Extraction:

Information on demographics, study dates, fracture grade, antibiotic type, duration and route of administration, surgical interventions, infection-related outcomes, and the methodologic quality of the studies was extracted by the authors. The primary results were submitted to the Therapeutic Agents Committee of the Surgical Infection Society for review prior to creation of the final consensus document.

Data Synthesis:

Current antibiotic management of open fractures is based on a small number of studies that generally are more than 30 years old and do not reflect current management priorities in trauma and critical care. With a few noteworthy exceptions, these primary studies suffer from a variety of methodologic problems, including commingling of prospective and retrospective data sets, absence of or inappropriate statistical analysis, lack of blinding, or failure of randomization.

PMID: 16978082 [PubMed - in process]

Friday, September 15, 2006

A Non-Nephrotoxic Gentamicin Congener That Retains Antimicrobial Efficacy.

A Non-Nephrotoxic Gentamicin Congener That Retains Antimicrobial Efficacy.

Sept 13, 2006

Sandoval RM,
Reilly JP,
Running W,
Campos SB,
Santos JR,
Phillips CL,
Molitoris BA.

*Indiana University School of Medicine, Division of Nephrology, Indiana Center for Biological Microscopy, Indiana University Department of Pathology & Laboratory Medicine, and paragraph signRoudebush Veterans Administration Medical Center, Indianapolis, and Indiana University Department of Chemistry, Bloomington, Indiana.

Aminoglycoside antibiotics, although of major clinical importance in the treatment of serious Gram- negative infections and a potential therapeutic agent in the amelioration of diseases that are characterized by premature stop mutations, are associated with a high incidence of acute renal failure. With the use of HPLC techniques, the four components (congeners) of gentamicin, the most commonly used aminoglycoside, were isolated and characterized. Described here is a congener with minimal cytotoxicity in cell culture and animal studies that retained normal bactericidal properties in both Bacillus subtilis and a multidrug-resistant form of Klebsiella pneumoniae.

Furthermore, in animal studies, this congener failed to induce the functional and pathologic changes that are characteristic of gentamicin nephrotoxicity that is seen with the native compound. Finally, internalization of this non-nephrotoxic component was unaltered, but the subcellular distribution was different from native gentamicin or the other three cytotoxic congeners. These studies have identified a component of the native gentamicin congener mixture that retains its bactericidal properties with minimal or no apparent nephrotoxicity.

PMID: 16971659 [PubMed - as supplied by publisher]

Friday, September 08, 2006

Impact of piperacillin resistance on the outcome of Pseudomonas ventilator-associated pneumonia.

Impact of piperacillin resistance on the outcome of Pseudomonas ventilator-associated pneumonia.

Sept 7, 2006

Combes A,
Luyt CE,
Fagon JY,
Wolff M,
Trouillet JL,
Chastre J.

Groupe Hospitalier Pitie-Salpetriere, Assistance Publique, Hopitaux de Paris Universite Pierre et Marie Curie, Paris 6, Service de Reanimation Medicale, Institut de Cardiologie, 47, boulevard de l'Hopital, 75651, Paris Cedex 13, France,


The impact of antibiotic resistance on the outcome of infections due to Gram-negative bacilli, especially Pseudomonas, remains highly controversial.


We evaluated the impact of piperacillin resistance on the outcomes of Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) for patients who had received appropriate empiric antibiotics before enrollment in the PNEUMA trial, a multicenter randomized study comparing 8 vs 15[Symbol: see text]days of antibiotics.


Despite similar characteristics at intensive care unit (ICU) admission, patients infected with piperacillin-resistant Pseudomonas strains were more acutely ill at VAP onset and had a higher 28-day mortality rate (37 vs 19%; P[Symbol: see text]=[Symbol: see text]0.04) than those with piperacillin-susceptible Pseudomonas VAP. Factors associated with 28-day mortality retained by multivariable analysis were: age (OR: 1.07; 95% CI: 1.03-1.12); female gender (OR: 4.00; 95% CI: 1.41-11.11); severe underlying comorbidities (OR: 2.73; 95% CI: 1.02-7.33); and SOFA score (OR: 1.17; 95% CI: 1.03-1.32), but piperacillin resistance did not reach statistical significance (OR: 2.00; 95% CI: 0.72-5.61). The VAP recurrence rates, either superinfection or relapse, and durations of mechanical ventilation and ICU stay did not differ as a function of Pseudomonas-resistance status.


For patients with Pseudomonas VAP benefiting from appropriate empiric antibiotics, piperacillin resistance was associated with increased disease severity at VAP onset and higher 28-day crude mortality; however, after controlling for confounders, piperacillin-resistance was no longer significantly associated with 28-day mortality. The VAP recurrence rates and durations of ICU stay and mechanical ventilation did not differ for susceptible and resistant strains.

PMID: 16957901
[PubMed - as supplied by publisher]

Friday, September 01, 2006

Antibiotics and Severe pseudomonal infections.

Antibiotics and Severe pseudomonal infections.

Curr Opin Crit Care. 2006 Oct;12(5):458-63.

Mutlu GM,
Wunderink RG.

Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.


To review the most recent data on severe Pseudomonas aeruginosa infections. The focus will be on clinical studies with an emphasis on the critically ill.


The frequency of P. aeruginosa as the etiologic agent of infections associated with high morbidity and mortality in hospitalized patients continues to increase. Unfortunately, pan-resistant isolates are now emerging as a significant clinical problem. Highly or pan-resistant isolates are associated with more frequent inappropriate initial therapy and increased mortality. Prevention relies on limitation of antibiotic pressure. Unfortunately, antibiotic class rotation has not resulted in persistent decreases in resistant isolates and the increased use of treatment protocols may actually increase selection.


Because of the frequency of antibiotic resistance in clinical isolates of P. aeruginosa and the high associated mortality, combination, broad-spectrum antibiotic therapy should be used for empiric coverage of suspected P. aeruginosa infections. Accurate diagnostic testing can help to discontinue unnecessary antibiotics and decrease the overall selective pressure. Increasing resistance without new antibiotic classes on the horizon suggests the need for better use of available antibiotics and an emphasis on innovative treatment strategies in the future.

PMID: 16943726 [PubMed - in process]