Life-threatening clostridial infections range from intoxications (e.g., food poisoning, tetanus) to necrotizing enteritis/colitis, bacteremia, myonecrosis, and toxic shock syndrome (TSS). Tetanus and botulism are discussed in Chaps. 140 and 141, respectively. Colitis due to C. difficile is discussed in Chap. 129.
Clostridial Wound Contamination
Of open traumatic wounds, 30–80% are reportedly contaminated with clostridial species. In the absence of devitalized tissue, the presence of clostridia does not necessarily lead to infection. In traumatic injuries, clostridia are isolated with equal frequency from both suppurative and well-healing wounds. Thus, diagnosis and treatment of clostridial infection should be based on clinical signs and symptoms and not solely on bacteriologic findings.
Polymicrobial Infections Involving Clostridia
Clostridial species may be found in polymicrobial infections also involving microbial components of the indigenous flora. In these infections, clostridia often appear in association with non-spore-forming anaerobes and facultative or aerobic organisms. Head and neck infections, conjunctivitis, brain abscess, sinusitis, otitis, aspiration pneumonia, lung abscess, pleural empyema, cholecystitis, septic arthritis, and bone infections all may involve clostridia. These conditions are often associated with severe local inflammation but may lack the characteristic systemic signs of toxicity and rapid progression seen in other clostridial infections. In addition, clostridia are isolated from ∼66% of intraabdominal infections in which the mucosal integrity of the bowel or respiratory system has been compromised. In this setting, C. ramosum, C. perfringens, and C. bifermentans are the most commonly isolated species. Their presence does not invariably lead to a poor outcome. Clostridia have been isolated from suppurative infections of the female genital tract (e.g., ovarian or pelvic abscess) and from diseased gallbladders. Although the most frequently isolated species is C. perfringens, gangrene is not typically observed; however, gas formation in the biliary system can lead to emphysematous cholecystitis, especially in diabetic patients. C. perfringens in association with mixed aerobic and anaerobic microbes can cause aggressive life-threatening type I necrotizing fasciitis or Fournier's gangrene.
The treatment of mixed aerobic/anaerobic infection of the abdomen, perineum, or gynecologic organs should be based on Gram's staining, culture, and antibiotic sensitivity information. Reasonable empirical treatment consists of ampicillin or ampicillin/sulbactam combined with either clindamycin or metronidazole (Table 142-1). Broader gram-negative coverage may be necessary if the patient has recently been hospitalized or treated with antibiotics. Such coverage can be obtained by substituting ticarcillin/clavulanic acid, piperacillin/sulbactam, or a penem antibiotic for ampicillin or by adding a fluoroquinolone or an aminoglycoside to the regimen.
Table 142-1 Treatment of Clostridial Infections |Favorite Table|Download (.pdf)
Table 142-1 Treatment of Clostridial Infections
|Condition||Antibiotic Treatment||Penicillin Allergy||Adjunctive Treatment/Note|
|Polymicrobial anaerobic infections involving clostridia (e.g., abdominal wall, gynecologic)|
Ampicillin (2 g IV q4h)
Clindamycin (600–900 mg IV q6–8h)
Ciprofloxacin (400 mg IV q6–8 h)
Vancomycin (1 g IV q12h)
Metronidazole (500 mg IV q6h)
Ciprofloxacin (400 mg IV q6–8h)
Empirical therapy should be initiated. Therapy should be based on Gram's stain and culture results and on sensitivity data when available. Add gram-negative coverage if indicated (see text).
Penicillin, 3–4 mU IV q4–6h
Clindamycin (600–900 mg IV q6–8h)
as for polymicrobial anaerobic infections (see above)
|Transient bacteremia without signs of systemic toxicity may be clinically insignificant.|
Penicillin G (4 mU IV q4–6 h)
Clindamycin (600–900 mg IV q6–8h)
Cefoxitin (2 g IV q6h)
Clindamycin (600–900 mg IV q6–8h)
|Emergent surgical exploration and thorough debridement are extremely important. Hyperbaric oxygen therapy may be considered after surgery and antibiotics have been initiated.|
Enteric Clostridial Infections
C. perfringens type A is one of the most common bacterial causes of food-borne illness in the United States and Canada. The foods typically implicated include improperly cooked meat and meat products (e.g., gravy) in which residual spores germinate and proliferate during slow cooling or insufficient reheating. Illness results from the ingestion of food containing at least ∼108 viable vegetative cells, which sporulate in the alkaline environment of the small intestine, producing C. perfringens enterotoxin in the process. The diarrhea that develops within 7–30 h of ingestion of contaminated food is generally mild and self-limiting; however, in the very young, the elderly, and the immunocompromised, symptoms are more severe and occasionally fatal. Enterotoxin-producing C. perfringens has been implicated as an etiologic agent of persistent diarrhea in elderly patients in nursing homes and tertiary-care institutions and has been considered to play a role in antibiotic-associated diarrhea without pseudomembranous colitis.
C. perfringens strains associated with food poisoning possess the gene (cpe) coding for enterotoxin, which acts by forming pores in host cell membranes. C. perfringens strains isolated from non-food-borne diseases, such as antibiotic-associated and sporadic diarrhea, carry cpe on a plasmid that may be transmitted to other strains. Several methods have been described for the detection ofC. perfringens enterotoxin in feces, including cell culture assay (Vero cells), enzyme-linked immunosorbent assay, reversed-phase latex agglutination, and polymerase chain reaction (PCR) amplification of cpe. Each method has its advantages and limitations.
Enteritis necroticans (gas gangrene of the bowel) is a fulminating clinical illness characterized by extensive necrosis of the intestinal mucosa and wall. Cases can occur sporadically in adults or as epidemics in people of all ages. Enteritis necroticans is caused by α toxin– and β toxin–producing strains of C. perfringens type C; β toxin is located on a plasmid and is mainly responsible for pathogenesis. This life-threatening infection causes ischemic necrosis of the jejunum. In Papua New Guinea during the 1960s, enteritis necroticans (known in that locale as pigbel) was found to be the most common cause of death in children; it has been associated with pig feasts and occurs both sporadically and in outbreaks. Intramuscular immunization against the β toxin resulted in a decreased incidence of the disease in Papua New Guinea. Enteritis necroticans has also been recognized in the United States, the United Kingdom, Germany (“darmbrand”), and other developed nations; especially affected are adults who are malnourished or who have diabetes, alcoholic liver disease, or neutropenia.
Necrotizing enterocolitis, a disease resembling enteritis necroticans but associated with C. perfringens type A, has been found in North America in previously healthy adults. It is also a serious gastrointestinal disease of low-birth-weight (premature) infants hospitalized in neonatal intensive care units. The etiology and pathogenesis of this disease have remained enigmatic for more than four decades. Pathologic similarities between necrotizing enterocolitis and enteritis necroticans include the pattern of small-bowel necrosis involving the submucosa, mucosa, and muscularis; the presence of gas dissecting the tissue planes; and the degree of inflammation. Enteritis necroticans most commonly involves the jejunum, whereas necrotizing enterocolitis affects the ileum and frequently the ileocecal valve. Both diseases may manifest as intestinal gas cysts, although this feature is more common in necrotizing enterocolitis. The sources of the gas, which contains hydrogen, methane, and carbon dioxide, are probably the fermentative activities of intestinal bacteria, including clostridia. Epidemiologic data support an important role for C. perfringens or other gas-producing microorganisms (e.g., C. neonatale, certain other clostridia, or Klebsiella species) in the pathogenesis of necrotizing enterocolitis.
Patients with suspected clostridial enteric infection should undergo nasogastric suction and receive IV fluids. Pyrantel is given by mouth, and the bowel is rested by fasting. Benzylpenicillin (1 mU) is given intravenously every 4 h, and the patient is observed for complications requiring surgery. Patients with mild cases recover without surgical intervention. If surgical indications are present (gas in the peritoneal cavity, absent bowel sounds, rebound tenderness, abdominal rigidity), however, the mortality rate ranges from 35% to 100%; fatal outcome is due in part to perforation of the intestine. As pigbel continues to be a common disease in Papua New Guinea, consideration should be given to the use of a C. perfringens type C toxoid vaccine in local areas. Two doses given 3–4 months apart are preventive.
Clostridium species are important causes of bloodstream infections. Molecular epidemiologic studies of anaerobic bacteremia have identified C. perfringens and C. tertium as the two most frequently isolated species; these organisms cause up to 79% and 5%, respectively, of clostridial bacteremias. Occasionally, C. perfringens bacteremia occurs in the absence of an identifiable infection at another site. When associated with myonecrosis, bacteremia has a grave prognosis.
C. septicum is also commonly associated with bacteremia. This species is isolated only rarely from the feces of healthy individuals but may be found in the normal appendix. More than 50% of patients whose blood cultures are positive for this organism have some gastrointestinal anomaly (e.g., diverticular disease) or underlying malignancy (e.g., carcinoma of the colon). In addition, a clinically important association of C. septicum bacteremia with neutropenia of any origin—and, more specifically, with neutropenic enterocolitis involving the terminal ileum or cecum—has been observed. Patients with diabetes mellitus, severe atherosclerotic cardiovascular disease, or anaerobic myonecrosis (gas gangrene) may also develop C. septicum bacteremia. C. septicum has been recovered from the bloodstream of cirrhotic patients, as have C. perfringens, C. bifermentans, and other clostridia. Infections of the bloodstream by C. sordellii and C. perfringens have been associated with TSS.
Bloodstream infection by C. tertium, either alone or in combination with C. septicum or C. perfringens, can be found in patients with serious underlying disease such as malignancy or acute pancreatitis, with or without neutropenic enterocolitis; the frequency has not been systematically studied. C. tertium may present special problems in terms of both identification and treatment. This organism may stain gram-negative; is aerotolerant; and is resistant to metronidazole, clindamycin, and cephalosporins.
Other clostridia from the C. clostridioforme group (including C. clostridioforme, C. hathewayi, and C. bolteae) can cause bacteremia.
The clinical importance of recognizing clostridial bacteremia—especially that due to C. septicum—and starting appropriate treatment immediately cannot be overemphasized. Patients with this condition usually are gravely ill, and infection may metastasize to distant anatomic sites, resulting in spontaneous myonecrosis (see next section). Alternative methods to identify these strains, such as PCR or other rapid diagnostic tests, are not currently available. Anaerobic blood cultures and Gram's stain interpretation remain the best diagnostic tests at this point.
Clostridial Skin and Soft-Tissue Infections
Histotoxic clostridial species such as C. perfringens, C. histolyticum, C. septicum, C. novyi, and C. sordellii cause aggressive necrotizing infections of the skin and soft tissues. These infections are attributable in part to the elaboration of bacterial proteases, phospholipases, and cytotoxins. Necrotizing clostridial soft-tissue infections are rapidly progressive and are characterized by marked tissue destruction, gas in the tissues, and shock; they frequently end in death. Severe pain, crepitus, brawny induration with rapid progression to skin sloughing, violaceous bullae, and marked tachycardia are characteristics found in the majority of patients.
Clostridial Myonecrosis (Gas Gangrene)
C. perfringens myonecrosis (gas gangrene) is one of the most fulminant gram-positive bacterial infections of humans. Even with appropriate antibiotic therapy and management in an intensive care unit, tissue destruction can progress rapidly. Gas gangrene is accompanied by bacteremia, hypotension, and multiorgan failure and is invariably fatal if untreated. Gas gangrene is a true emergency and requires immediate surgical debridement.
The development of gas gangrene requires an anaerobic environment and contamination of a wound with spores or vegetative organisms. Devitalized tissue, foreign bodies, and ischemia reduce locally available oxygen levels and favor outgrowth of vegetative cells and spores. Thus conditions predisposing to traumatic gas gangrene include crush-type injury, laceration of large or medium-sized arteries, and open fractures of long bones that are contaminated with soil or bits of clothing containing the bacterial spores. Gas gangrene of the abdominal wall and flanks follows penetrating injuries such as knife or gunshot wounds that are sufficient to compromise intestinal integrity, with resultant leakage of the bowel contents into the soft tissues. Proximity to fecal sources of bacteria is a risk factor for cases following hip surgery, adrenaline injections into the buttocks, or amputation of the leg for ischemic vascular disease. In the last decade, cutaneous gas gangrene caused by C. perfringens, C. novyi, and C. sordellii has been described in the United States and northern Europe among persons injecting black-tar heroin subcutaneously.
The incubation period for traumatic gas gangrene can be as short as 6 h and is usually <4 days. The infection is characterized by the sudden onset of excruciating pain at the affected site and the rapid development of a foul-smelling wound containing a thin serosanguineous discharge and gas bubbles. Brawny edema and induration develop and give way to cutaneous blisters containing bluish to maroon-colored fluid. Such tissue later may become liquefied and slough. The margin between healthy and necrotic tissue often advances several inches per hour despite appropriate antibiotic therapy, and radical amputation remains the single best life-saving intervention. Shock and organ failure frequently accompany gas gangrene; when patients become bacteremic, the mortality rate exceeds 50%.
Diagnosis of traumatic gas gangrene is not difficult because the infection always begins at the site of significant trauma, is associated with gas in the tissue, and is rapidly progressive. Gram's staining of drainage or tissue biopsy is usually definitive, demonstrating large gram-positive (or gram-variable) rods, an absence of inflammatory cells, and widespread soft-tissue necrosis.
Spontaneous (Nontraumatic) Gas Gangrene
Spontaneous gas gangrene generally occurs via hematogenous seeding of normal muscle with histotoxic clostridia—principally C. perfringens, C. septicum, and C. novyi and occasionally C. tertium—from a gastrointestinal tract portal of entry (as in colonic malignancy, inflammatory bowel disease, diverticulitis, necrotizing enterocolitis, cecitis, or distal ileitis or after gastrointestinal surgery). These gastrointestinal pathologies permit bacterial access to the bloodstream; consequently, aerotolerant C. septicum can proliferate in normal tissues. Patients surviving bacteremia or spontaneous gangrene due to C. septicum should undergo aggressive diagnostic studies to rule out gastrointestinal pathology.
Additional predisposing host factors include leukemia, lympho-proliferative disorders, cancer chemotherapy, radiation therapy, and AIDS. Cyclic, congenital, or acquired neutropenia is also strongly associated with an increased incidence of spontaneous gas gangrene due to C. septicum; in such cases, necrotizing enterocolitis, cecitis, or distal ileitis is common, particularly among children.
The first symptom of spontaneous gas gangrene may be confusion followed by the abrupt onset of excruciating pain in the absence of trauma. These findings, along with fever, should heighten suspicion of spontaneous gas gangrene. However, because of the lack of an obvious portal of entry, the correct diagnosis is frequently delayed or missed. The infection is characterized by rapid progression of tissue destruction with demonstrable gas in the tissue (Fig. 142-2). Swelling increases and bullae filled with clear, cloudy, hemorrhagic, or purplish fluid appear. The surrounding skin has a purple hue, which may reflect vascular compromise resulting from the diffusion of bacterial toxins into surrounding tissues. Invasion of healthy tissue rapidly ensues, with quick progression to shock and multiple-organ failure. Mortality rates in this setting range from 67 to 100% among adults; among children, the mortality rate is 59%, with the majority of deaths occurring within 24 h of onset.
Radiograph of patient with spontaneous gas gangrene due to C. septicum, demonstrating gas in the affected arm and shoulder.
Pathogenesis of Gas Gangrene
In traumatic gas gangrene, organisms are introduced into devitalized tissue. It is important to recognize that for C. perfringens and C. novyi, trauma must be sufficient to interrupt the blood supply and thereby to establish an optimal anaerobic environment for growth of these species. These conditions are not strictly required for the more aerotolerant species such as C. septicum and C. tertium, which can seed normal tissues from gastrointestinal lesions. Once introduced into an appropriate niche, the organisms proliferate locally and elaborate exotoxins.
The major C. perfringens extracellular toxins implicated in gas gangrene are α toxin and θ toxin. A lethal hemolysin that has both phospholipase C and sphingomyelinase activities, α toxin has been implicated as the major virulence factor of C. perfringens: immunization of mice with the C-terminal domain of α toxin provides protection against lethal challenge with C. perfringens, and isogenic α toxin–deficient mutant strains of C. perfringens are not lethal in a murine model of gas gangrene. It has been shown in experimental models that the severe pain, rapid progression, marked tissue destruction, and absence of neutrophils in C. perfringens gas gangrene are attributable in large part to α toxin–induced occlusion of blood vessels by heterotypic aggregates of platelets and neutrophils. The formation of these aggregates, which occurs within minutes, is largely mediated by α toxin's ability to activate the platelet adhesion molecule gpIIbIIIa (Fig. 142-3); the implication is that platelet glycoprotein inhibitors (e.g., eptifibatide, abciximab) may be therapeutic for maintaining tissue blood flow.
Schematic illustration of the molecular mechanisms of C. perfringens α toxin–induced platelet/neutrophil aggregates. Homotypic aggregates of platelets (not shown) and heterotypic aggregates of platelets and leukocytes are due to α toxin–induced activation of the platelet fibrinogen receptor gpIIbIIIa and upregulation of leukocyte CD11b/CD18. Binding of fibrinogen (red) bridges the connection between these adhesion molecules on adjacent cells. An auxiliary role for α toxin–induced upregulation of platelet P-selectin and its binding to leukocyte P-selectin glycoprotein ligand 1 (PSGL-1) or other leukocyte surface carbohydrates has also been demonstrated.
C. perfringens θ toxin (perfringolysin) is a member of the thiol-activated cytolysin family known as cholesterol-dependent cytolysins, which includes streptolysin O from group A Streptococcus, pneumolysin from Streptococcus pneumoniae, and several other toxins. Cholesterol-dependent cytolysins bind as oligomers to cholesterol in host cell membranes. At high concentrations, these toxins form ring-like pores resulting in cell lysis. At sublytic concentrations, θ toxin hyperactivates phagocytes and vascular endothelial cells.
Cardiovascular collapse and end-organ failure occur late in the course of C. perfringens gas gangrene and are largely attributable to both direct and indirect effects of α and θ toxins. In experimental models, θ toxin causes markedly reduced systemic vascular resistance but increased cardiac output (e.g., “warm shock”), probably via induction of endogenous mediators (e.g., prostacyclin, platelet-activating factor) that cause vasodilation. This effect is similar to that observed in gram-negative sepsis. In sharp contrast, α toxin directly suppresses myocardial contractility; the consequence is profound hypotension due to a sudden reduction in cardiac output. The roles of other endogenous mediators, such as cytokines (e.g., tumor necrosis factor, interleukin 1, interleukin 6) and vasodilators (e.g., bradykinin) have not been fully elucidated.
C. septicum produces four main toxins—α toxin (lethal, hemolytic, necrotizing activity), β toxin (DNase), γ toxin (hyaluronidase), and Δ" toxin (septicolysin, an oxygen-labile hemolysin)—as well as a protease and a neuraminidase. Unlike the α toxin of C. perfringens, that of C. septicum does not possess phospholipase activity. The mechanisms remain to be fully elucidated, but it is likely that each of these toxins contributes uniquely to C. septicum gas gangrene.
Patients with suspected gas gangrene (either traumatic or spontaneous) should undergo prompt surgical inspection of the infected site. Direct examination of a gram-stained smear of the involved tissues is of major importance. Characteristic histologic findings in clostridial gas gangrene include widespread tissue destruction, a paucity of leukocytes in infected tissues in conjunction with an accumulation of leukocytes in adjacent vessels (Fig. 142-4), and the presence of gram-positive rods (with or without spores). CT and MRI are invaluable for determining whether the infection is localized or is spreading along fascial planes, and needle aspiration or punch biopsy may provide an etiologic diagnosis in at least 20% of cases. However, these techniques should not replace surgical exploration, Gram's staining, and histopathologic examination. When spontaneous gas gangrene is suspected, blood should be cultured since bacteremia usually precedes cutaneous manifestations by several hours.
Histopathology of experimental gas gangrene due to C. perfringens, demonstrating widespread muscle necrosis, a paucity of leukocytes in infected tissues, and accumulation of leukocytes in adjacent vessels (arrows). These features are due to the effects of α and θ toxins on muscle cells, platelets, leukocytes, and endothelial cells.
For patients with evidence of clostridial gas gangrene, thorough emergent surgical debridement is of extreme importance. All devitalized tissue should be widely resected back to healthy viable muscle and skin so as to remove conditions that allow anaerobic organisms to continue proliferating. Closure of traumatic wounds or compound fractures should be delayed for 5–6 days until it is certain that these sites are free of infection.
Antibiotic treatment of traumatic or spontaneous gas gangrene (Table 142-1) consists of the administration of penicillin and clindamycin for 10–14 days. Penicillin is recommended on the basis of in vitro sensitivity data; clindamycin is recommended because of its superior efficacy over penicillin in animal models of C. perfringens gas gangrene and in some clinical reports. Controlled clinical trials comparing the efficacy of these agents in humans have not been performed. In the penicillin-allergic patient, clindamycin may be used alone. The superior efficacy of clindamycin is probably due to its ability to inhibit bacterial protein toxin production, its insensitivity to the size of the bacterial load or the stage of bacterial growth, and its ability to modulate the host's immune response.
C. tertium is resistant to penicillin, cephalosporins, and clindamycin. Appropriate antibiotic therapy for C. tertium infection is vancomycin (1 g every 12 h IV) or metronidazole (500 mg every 8 h IV).
The value of adjunctive treatment with hyperbaric oxygen (HBO) for gas gangrene remains controversial. Basic science studies suggest that HBO can inhibit the growth of C. perfringens but not that of the more aerotolerant C. septicum. In vitro, blood and macerated muscle inhibit the bactericidal potential of HBO. Numerous studies in animals demonstrate little efficacy of HBO alone, whereas antibiotics alone—especially those that inhibit bacterial protein synthesis—confer marked benefits. Addition of HBO to the therapeutic regimen provides some additional benefit, but only if surgery and antibiotic administration precede HBO treatment.
In conclusion, gas gangrene is a rapidly progressive infection whose outcome depends on prompt recognition, emergent surgery, and timely administration of antibiotics that inhibit toxin production. Gas gangrene associated with bacteremia probably represents a later stage of illness and is associated with the worst outcomes. Emergent surgical debridement is crucial to ensure survival, and ancillary procedures (e.g., CT or MRI) or transport to HBO units should not delay this intervention. Some trauma centers associated with HBO units may have special expertise in managing these aggressive infections, but proximity and speed of transfer must be carefully weighed against the need for haste.
Prognosis of Gas Gangrene
The prognosis for patients with gas gangrene is more favorable when the infection involves an extremity rather than the trunk or visceral organs, since debridement of the latter sites is more difficult. Gas gangrene is most likely to progress to shock and death in patients with associated bacteremia and intravascular hemolysis. Mortality rates are highest for patients in shock at the time of diagnosis. Mortality rates are relatively high among patients with spontaneous gas gangrene, especially that due toC. septicum. Survivors of gas gangrene may undergo multiple debridements and face long periods of hospitalization and rehabilitation.
Prevention of Gas Gangrene
Initial aggressive debridement of devitalized tissue can reduce the risk of gas gangrene in contaminated deep wounds. Interventions to be avoided include prolonged application of tourniquets and surgical closure of traumatic wounds; patients with compound fractures are at significant risk for gas gangrene if the wound is closed surgically. Vaccination against α toxin is protective in experimental animal models of C. perfringens gas gangrene but has not been investigated in humans. In addition, as mentioned above, a hyperimmune globulin would represent a significant advance for prophylaxis in victims of acute traumatic injury or for attenuation of the spread of infection in patients with established gas gangrene.
Clostridial infection of the endometrium, particularly that due to C. sordellii, can develop after gynecologic procedures, childbirth, or abortion (spontaneous or elective, surgical or medical) and, once established, proceeds rapidly to TSS and death. Systemic manifestations including edema, effusions, profound leukocytosis, and hemoconcentration are followed by the rapid onset of hypotension and multiple-organ failure. Elevation of the hematocrit to 75–80% and leukocytosis of 50,000–200,000 cells per microliter, with a left shift, are characteristic of C. sordellii infection. Pain may not be a prominent feature, and fever is typically absent. In one series, 18% of 45 cases of C. sordellii infection were associated with normal childbirth, 11% with medically induced abortion, and 0.4% with spontaneous abortion; the case-fatality rate was 100% in these groups. Of the infections in this series that were not related to gynecologic procedures or childbirth, 22% occurred in injection drug users, and 50% of these patients died. Other infections followed trauma or surgery (42%), mostly in healthy persons, and 53% of these patients died. Overall, the mortality rate was 69% (31 of45 cases). Of patients who succumbed, 85% died within 2–6 days of initial infection or following procedures.
Early diagnosis of C. sordellii infections often proves difficult for several reasons. First, the prevalence of these infections is low. Second, the initial symptoms are nonspecific and frankly misleading. Early in the course, the illness resembles any number of infectious diseases, including viral syndromes. Given these vague symptoms and an absence of fever, physicians usually do not aggressively pursue additional diagnostic tests. The absence of local evidence of infection and the lack of fever make early diagnosis ofC. sordellii infection particularly problematic in patients who develop deep-seated infection following childbirth, therapeutic abortion, gastrointestinal surgery, or trauma. Such patients are frequently evaluated for pulmonary embolization, gastrointestinal bleeding, pyelonephritis, or cholecystitis. Unfortunately, such delays in diagnosis increase the risk of death, and, as in most necrotizing soft-tissue infections, patients are hypotensive with evidence of organ dysfunction by the time local signs and symptoms become apparent. In contrast, infection is more readily suspected in injection drug users presenting with local swelling, pain, and redness at injection sites; early recognition probably contributes to the lower mortality rates in this group.
Physicians should suspect C. sordellii infection in patients who present within 2–7 days after injury, surgery, drug injection, childbirth, or abortion and who complain of pain, nausea, vomiting, and diarrhea but are afebrile. There is little information regarding appropriate treatment for C. sordellii infections. In fact, the interval between onset of symptoms and death is often so short that there is little time to initiate empirical antimicrobial therapy. Indeed, anaerobic cultures of blood and wound aspirates are time-consuming, and many hospital laboratories do not routinely perform antimicrobial sensitivity testing on anaerobes. Antibiotic susceptibility data from older studies suggest that C. sordellii, like most clostridia, is susceptible to β-lactam antibiotics, clindamycin, tetracycline, and chloramphenicol but is resistant to aminoglycosides and sulfonamides. Antibiotics that suppress toxin synthesis (e.g., clindamycin) may possibly prove useful as therapeutic adjuncts since they are effective in necrotizing infections due to other toxin-producing gram-positive organisms.
Other Clostridial Skin and Soft-Tissue Infections
Crepitant cellulitis (also called anaerobic cellulitis) occurs principally in diabetic patients and characteristically involves subcutaneous tissues or retroperitoneal tissues, whereas the muscle and fascia are not involved. This infection can progress to fulminant systemic disease.
Cases of C. histolyticum infection with cellulitis, abscess formation, or endocarditis have also been documented in injection drug users. Endophthalmitis due to C. sordellii or C. perfringens has been described. C. ramosum is also isolated frequently from clinical specimens, including blood and intraabdominal and soft tissues. This species may be resistant to clindamycin and multiple cephalosporins.