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Clostridial Myonecrosis
(Gas Gangrene)
Clinical Manifestations
Onset is heralded by acute pain at the site of the wound, followed by edema, increasing exquisite tenderness, exudate, and progression of pain. Systemic findings initially include tachycardia disproportionate to the degree of fever, pallor, diaphoresis, hypotension, renal failure, and then, later, alterations in mental status. Crepitus is suggestive but not pathog- nomonic of Clostridium infection and is not always present. Diagnosis is based on clinical manifestations including the characteristic appearance of necrotic muscle at surgery.
Untreated gas gangrene can lead to dissemi- nated myonecrosis, suppurative visceral infec- tion, septicemia, and death within hours.
Etiology
Clostridial myonecrosis is caused by Clostrid
ium species, most often Clostridium perfrin
gens. These organisms are large, gram-positive, spore-forming, anaerobic bacilli with blunt ends. Other Clostridium species (eg, Clostrid
ium sordellii, Clostridium septicum, Clostrid
ium novyi) have also been associated with myonecrosis. Disease manifestations are caused by potent clostridial exotoxins (eg, C sordellii with medical abortion; C septicum with malignancy). Mixed infection with other gram-positive and gram-negative bacteria is common.
Epidemiology
Clostridial myonecrosis usually results from contamination of open wounds involving muscle. The sources of Clostridium species are soil, contaminated foreign bodies, and human and animal feces. Dirty surgical or traumatic wounds, particularly those with retained foreign bodies or significant amounts of devitalized tissue, predispose to disease.
Nontraumatic gas gangrene occurs rarely in people who are immunocompromised, most
often in those with underlying malignancy, neutrophil dysfunction, or diseases associated with bowel ischemia.
Incubation Period From injury, 1 to 4 days.
Diagnostic Tests
Anaerobic cultures of wound exudate, involved soft tissue and muscle, and blood should be performed. Because Clostridium species are ubiquitous, their recovery from a wound is not diagnostic unless typical clinical manifesta- tions are present. A Gram-stained smear of wound discharge demonstrating characteristic gram-positive bacilli and few, if any, polymor- phonuclear leukocytes suggests clostridial infection. Tissue specimens (not swab speci- mens) for anaerobic culture must be obtained to confirm the diagnosis. Because some patho- genic Clostridium species are exquisitely oxy- gen sensitive, care should be taken to optimize anaerobic growth conditions. A radiograph of the affected site can demonstrate gas in the tissue, but this is a nonspecific finding. Occa- sionally, blood culture results are positive and are considered diagnostic.
Treatment
Prompt and complete surgical excision of necrotic tissue and removal of foreign material are essential. Repeated surgical debridement may be required. Management of shock, fluid and electrolyte imbalance, hemolytic anemia, and other complications is crucial. High-dose penicillin G should be administered intrave- nously. Clindamycin, metronidazole, mero- penem, ertapenem, and chloramphenicol can be considered as alternative drugs for patients with a serious penicillin allergy or for treat- ment of polymicrobial infections. The combi- nation of penicillin G and clindamycin may be superior to penicillin alone because of the theoretical benefit of clindamycin inhibiting toxin synthesis. Hyperbaric oxygen may be beneficial, but efficacy data from adequately controlled clinical studies are not available.
110 CLOSTriDiAL myONECrOSiS
Image 31.1
Gram stain of a tissue aspirate from a patient with clostridial omphalitis showing the charac teristic morphology of Clostridia bacilli, erro neously stained gram-negative, and sparse polymorphonuclear leukocytes.
Image 31.2
Clostridial omphalitis in an infant with myone crosis of the abdominal wall (periumbilical). Early and complete surgical excision of necrotic tissue and careful management of shock, fluid balance, and other complications are crucial for survival.
CLOSTRIDIUM DIFFICILE 111
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Clostridium difficile
Clinical Manifestations
Clostridium difficile is associated with several syndromes as well as with asymptomatic car- riage. Mild to moderate illness is characterized by watery diarrhea, low-grade fever, and mild abdominal pain. Pseudomembranous entero- colitis is characterized by diarrhea with mucus in feces, abdominal cramps and pain, fever, and systemic toxicity. Occasionally, children have marked abdominal tenderness and disten- tion with minimal diarrhea (toxic megacolon).
The colonic mucosa often contains 2- to 5-mm, raised, yellowish plaques. Disease often begins while the child is hospitalized receiving anti- microbial therapy but can occur up to 10 weeks after therapy cessation. Community-associated C difficile disease is less common but is increas- ing in frequency. The illness usually, but not always, is associated with antimicrobial ther- apy or prior hospitalization. Complications, which occur more commonly in older adults, can include toxic megacolon, intestinal perfo- ration, systemic inflammatory response syn- drome, and death. Severe or fatal disease is more likely to occur in neutropenic children with leukemia, infants with Hirschsprung disease (congenital megacolon), and patients with inflammatory bowel disease. Colonization with C difficile, including toxin-producing strains, occurs in children younger than 5 years and is most common in infants. It is unclear how frequently C difficile causes disease in infants younger than 1 year.
Etiology
Clostridium difficile is a spore-forming, obligate anaerobic, gram-positive bacillus.
Disease is related to A and B toxins produced by these organisms.
Epidemiology
C difficile can be isolated from soil and is commonly found in the hospital environment.
C difficile is acquired from the environment or from stool of other colonized or infected peo- ple by the fecal-oral route. Intestinal coloniza- tion rates in healthy infants can be as high as 50% but usually are less than 5% in children
older than 5 years and adults. Hospitals, nurs- ing homes, and child care facilities are major reservoirs for C difficile. Risk factors for acqui- sition of the bacteria include prolonged hospi- talization and exposure to an infected person in the hospital or the community. Risk factors for C difficile disease include antimicrobial therapy, repeated enemas, gastric acid sup- pression therapy, prolonged nasogastric tube placement, gastrostomy and jejunostomy tubes, underlying bowel disease, gastrointestinal tract surgery, renal insufficiency, and humoral immunocompromise. C difficile colitis has been associated with exposure to almost every antimicrobial agent. Hospitalization of chil- dren for C difficile colitis is increasing. The NAP1 strain, a more virulent strain of C diffi
cile with variations in toxin genes, is associated with severe disease, has emerged as a cause of outbreaks among adults, and has been reported in children.
Incubation Period
Unknown; colitis usually develops 5 to 10 days after initiation of antimicrobial therapy.
Diagnostic Tests
The diagnosis of C difficile disease is based on the presence of diarrhea and detection of C difficile toxins in a diarrheal specimen.
Isolation of the organism or toxin detection from the stool of a patient who is not having liquid stools (unless toxic megacolon is sus- pected) should not be performed. Endoscopic findings of pseudomembranes and hyperemic, friable rectal mucosa suggest pseudomembra- nous enterocolitis. The most common testing method for C difficile toxins is the commer- cially available enzyme immunoassay (EIA), which detects toxins A and B. Although EIAs are rapid and performed easily, their sensitivity is relatively low. The cell culture cytotoxicity assay, which also tests for toxin in stool, is more sensitive but requires more labor and has a slow turnaround time, limiting its use- fulness in the clinical setting. Two-step testing algorithms that use sensitive but nonspecific (detects toxigenic and nontoxigenic strains) glutamate dehydrogenase EIA combined with confirmatory toxin testing of positive results can also be used. Molecular assays using nucleic acid amplification tests (NAATs) have
112 CLOSTRIDIUM DIFFICILE
been developed; NAATs combine good sensi- tivity and specificity, provide results to clini- cians in times comparable with EIAs, and are not required to be part of a 2- or 3-step algo- rithm. Many children’s hospitals are convert- ing to NAAT technology to diagnose C difficile infection, but more data are needed in children before this technology can be used routinely as a stand-alone test. The predictive value of a positive NAAT result in a child younger than 5 years is unknown because carriage of toxi- genic strains often occurs in these children.
Because colonization with C difficile in infants is common, testing for other causes of diarrhea is always recommended in these patients.
C difficile toxin degrades at room temperate and can be undetectable within 2 hours after collection of a stool specimen. Tests of cure should not be performed.
Treatment
Precipitating antimicrobial therapy should be discontinued as soon as possible. Antimicro- bial therapy for C difficile infection is always indicated for symptomatic patients. C difficile is susceptible to metronidazole and vancomy- cin. Metronidazole, orally, is the drug of choice for initial treatment of children and adoles- cents with mild to moderate diarrhea and for first relapse. Oral vancomycin or vancomycin administered by enema plus intravenous met-
ronidazole is indicated as initial therapy for patients with severe disease (ie, hospitalized in an intensive care unit, pseudomembranous enterocolitis by endoscopy, or significant underlying intestinal tract disease) and for patients who do not respond to oral metro- nidazole. Vancomycin for intravenous use can be prepared for oral use. Intravenously administered vancomycin is not effective for C difficile infection. Therapy with metronida- zole or vancomycin or the combination should be administered for at least 10 days.
Up to 25% of patients experience a relapse after discontinuing therapy, but infection usually responds to a second course of the same treat- ment. Metronidazole should not be used for treatment of a second recurrence or for chronic therapy because neurotoxicity is possible.
Tapered or pulse regimens of vancomycin are recommended under this circumstance. Fidax- omicin and nitazoxanide have been approved for treatment of C difficile–associated diarrhea in adults, but no pediatric data are available for fidaxomicin. Nitazoxanide is also an effec- tive therapy in adults. Drugs that decrease intestinal motility should not be administered.
Follow-up testing for toxin is not recom- mended. Fecal transplant (intestinal micro- biota transplantation) appears to be effective in adults; there are limited data in pediatrics.
Image 32.1
Clostridium difficile is a gram-positive, spore-forming bacteria that can be part of the normal intestinal flora in as many as 50% of children younger than 2 years. it is a cause of pseudo membranous enterocolitis and antibiotic-associated diarrhea in older children and adults. Courtesy of AAP News.
CLOSTRIDIUM DIFFICILE 113
Image 32.2
This photograph depicts Clostridium difficile colonies after 48 hours’ growth on a blood agar plate (magnification x4.8). Courtesy of Centers for Disease Control and Prevention/Dr Holdeman.
Image 32.3
This micrograph depicts gram-positive Clostridium difficile from a stool sample culture obtained using a 0.1-µm filter. People can become infected if they touch items or surfaces that are contaminated with C difficile spores and then touch their mouths or mucous membranes. Health care workers can spread the bacteria to other patients or contaminate surfaces through hand contact. Courtesy of Lois Higg/
Courtesy of Centers for Disease Control and Prevention.
Image 32.4
The right-hand panel shows the typical pseudo membranes of Clostridium difficile colitis; the left-hand panel shows the histology, with the pseudomembrane structure at the top middle (arrows). Courtesy of Carol J. Baker, mD, FAAP.
114 CLOSTRIDIUM PERFRINGENS FOOD POiSONiNG
33
Clostridium perfringens Food Poisoning
Clinical Manifestations
Clostridium perfringens foodborne illness is characterized by a sudden onset of watery diarrhea and moderate to severe, cramping, midepigastric pain. Vomiting and fever are uncommon. Symptoms usually resolve within 24 hours. The short incubation period, short duration, and absence of fever in most patients differentiate C perfringens foodborne disease from shigellosis and salmonellosis, and the infrequency of vomiting and longer incubation period contrast with the clinical features of foodborne disease associated with heavy metals, Staphylococcus aureus enterotoxins, Bacillus cereus emetic toxin, and fish and shell- fish toxins. Diarrheal illness caused by B cereus diarrheal enterotoxins can be indistinguishable from that caused by C perfringens. Enteritis necroticans (also known as pigbel) results from hemorrhagic necrosis of the midgut and is a cause of severe illness and death attributable to C perfringens food poisoning caused by Clostridium β toxin. Rare cases have been reported in the Highlands of Papua, in New Guinea, and in Thailand; malnutrition is an important risk factor.
Etiology
Typical food poisoning is caused by a heat- labile C perfringens enterotoxin. C perfringens type A, which produces α toxin and entero- toxin, commonly causes foodborne illness.
Enteritis necroticans is caused by C perfringens type C, which produces α and β toxins and enterotoxin.
Epidemiology
C perfringens is a gram-positive, spore-forming bacillus that is ubiquitous in the environment and the intestinal tracts of humans and ani- mals and is commonly present in raw meat and poultry. Spores of C perfringens that survive cooking can germinate and multiply rapidly
during slow cooling, when stored at tempera- tures from 20°C to 60°C (68°F–140°F), and during inadequate reheating. At an optimum temperature, C perfringens has one of the fastest rates of growth of any bacterium. Ill- ness results from consumption of food con- taining high numbers of vegetative organisms (>105 colony-forming units [CFU]/g) followed by enterotoxin production in the intestine.
Beef, poultry, gravies, and dried or precooked foods are common sources. Ingestion of the organism is most commonly associated with foods prepared by restaurants or caterers or in institutional settings (eg, schools, camps) where food is prepared in large quantities, cooled slowly, and stored inappropriately for prolonged periods. Illness is not transmissible from person to person.
Incubation Period
6 to 24 hours; usually 8 to 12 hours.
Diagnostic Tests
Because the fecal flora of healthy people commonly includes C perfringens, counts of C perfringens of 106 CFU/g of feces or greater obtained within 48 hours of onset of illness are required to support the diagnosis in ill people.
The diagnosis also can be supported by detec- tion of enterotoxin in stool. C perfringens can be confirmed as the cause of an outbreak if 106 CFU/g are isolated from stool or entero- toxin is demonstrated in the stool of 2 or more ill people or when the concentration of organ- isms is at least 105/g in the epidemiologically implicated food. Although C perfringens is an anaerobe, special transport conditions are unnecessary. Stool specimens, rather than rec- tal swab specimens, should be obtained, trans- ported in ice packs, and tested within 24 hours.
Treatment
Oral rehydration or, occasionally, intravenous fluid and electrolyte replacement may be indi- cated to prevent or treat dehydration. Antimi- crobial agents are not indicated.
CLOSTRIDIUM PERFRINGENS FOOD POiSONiNG 115
Image 33.1
This photomicrograph reveals numbers of Clostridium perfringens bacteria grown in Schaedler broth and subsequently stained using Gram stain (magnification x1,000). C perfringens is a spore-forming, heat-resistant bacterium that can cause foodborne disease. The spores persist in the environment and often contaminate raw food materials. These bacteria are found in mammalian feces and soil. Courtesy of Centers for Disease Control and Prevention/Don Stalons.
Image 33.2
This photomicrograph reveals Clostridium perfringens grown in Schaedler broth using Gram stain. Courtesy of Centers for Disease Control and Prevention/Don Stalons.
Image 33.3
Clostridium perfringens, an anaerobic, gram-positive, spore-forming bacillus, causes a broad spectrum of pathology, including food poisoning. in Papua New Guinea, C perfringens is a cause of severe illness and death called necrotizing enteritis necroticans (locally known as pigbel). Courtesy of Hugh moffet, mD.
Image 33.4
This slide shows hemorrhagic necrosis of the intestine in a patient with Clostridium perfringens sepsis.
Courtesy of Dimitris P. Agamanolis, mD.
116 COCCiDiOiDOmyCOSiS
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