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Clostridium innocuum is an unusual cause of infections in humans. This report describes the first published case of C. innocuum bacteremia in an AIDS patient and provides a review of the literature. The case suggests that recent C. difficile infection may be a risk factor for the subsequent development of C. innocuum bacteremia among immunosuppressed persons. Due to their intrinsic resistance to several common antibiotics, including vancomycin, C. innocuum infections are important to recognize.
Clostridia species are gram-positive anaerobes that are normal flora of the oropharynx and gastrointestinal tract. Most clostridial infections are due to C. perfringens or C. septicum, whereas C. innocuum is a more unusual cause of infections in humans . Prior case reports have described C. innocuum as a cause of abdominal sepsis and, rarely, bacteremia [2–4]. This report describes the first reported case of C. innocuum bacteremia in an AIDS patient.
A 38-year-old African American male with AIDS was admitted for low grade fevers. He had previously been hospitalized for Clostridium difficile colitis and a necrotizing soft tissue infection of the right leg, which was culture-positive for methicillin-resistant Staphylococcus aureus (MRSA). Treatment consisted of daptomycin, imipenem, and oral vancomycin. The patient had a 12-year history of HIV infection; he had a CD4 count of 76 cells/mm3 and a HIV viral load of >100,000 copies/ml. He had self-discontinued his HIV regimen. The patient had also been diagnosed with abdominal adenopathy and diarrhea due to Mycobacterium avium infection, but refused the multi-drug therapy.
On the day of admission, examination revealed a temperature of 100.8 °F, pulse of 93, and blood pressure of 104/48. His examination was noteworthy for a healing right leg wound. Abdominal examination was mildly distended, but there were no masses or hepatosplenomegaly. Laboratory investigation showed a white blood count of 6,000/ mm3 with 90% neutrophils, hemoglobin of 7.1 mg/dl, and platelet count of 64,000/mm3. Chemistries were unremarkable except for a mildly elevated creatinine (1.5 mg/dl); liver function tests were normal. Stool studies and blood cultures were obtained on admission.
Due to concerns of continued infection of the leg and possible recurrent C. difficile colitis, daptomycin 4 mg/kg daily and oral metronidazole was begun. An anaerobic blood culture from admission became positive on hospital day three for a gram-positive rod. The organism was identified as a clostridium species, initially thought to be C. difficile. Three stool specimens were negative for C. difficile toxin, and an abdominal film showed mild obstruction without toxic megacolon. The blood isolate was sent to the Centers for Disease Control and Prevention (CDC) in Atlanta for further identification. The organism was an anaerobe, 1–2 mm in colony diameter, had yellow-green fluorescence, and was esculin positive. Further biochemical evaluation and fermentation tests identified the organism as Clostridium innocuum. The isolate was resistant to vancomycin. Therapy with metronidazole and daptomycin was continued and follow-up blood cultures were negative. The patient was switched to an oral regimen of metronidazole and linezolid for the C. innocuum bacteremia and wound infection with MRSA completing a total of 10 days of antibiotics. He restarted antiretroviral therapy and has had no further episodes of bacteremia.
Clostridium innocuum was first described in human infections in the 1960s . The name “innocuum” was chosen as a result of the organism’s proposed lack of virulence. Although the organism was thought to be non-pathogenic due to the lack of toxin production, infections have been reported, especially among immunocompromised hosts. Clostridial species are inhabitants of the gastrointestinal tract; hence, compromise of the integrity gastrointestinal tract may lead to translocation with bacteremia. In the current case, previous C. difficile colitis may have predisposed to the C. innocuum bacteremia as suggested by another report . This case may have an additional risk for C. innocuum bacteremia including a M. avium infection of the gastrointestinal tract.
A literature review was conducted using Ovid MEDLINE (1950–2008) and EMBASE (1980 to 2008) and the terms “Clostridium innocuum” and “bacteremia”; references of papers were also utilized to locate further cases. The review of the literature found 13 cases of C. innocuum bacteremia or endocarditis, including this case (Table 1) [1, 4, 7]. Three other cases of bacteremia were noted in the literature, but did not include details of the individual cases [2, 8]. The median age of cases was 38 years (range 18–70 years), and 62% were male. All but one case had an immunocompromising condition, including malignancy (n=10), organ transplantation (n=1) and AIDS (n=1). This concurs with other reports suggesting that infections with “non-perfringens” clostridial species have a propensity to develop in immunocompromised hosts . The most common presenting symptom of C. innocuum bacteremia was fevers of unknown etiology, with gastrointestinal symptoms being the second most common clinical manifestation.
Identification of C. innocuum is often more difficult than other clostridial species which are usually identified by simple laboratory tests. Members of the RIC group (C. ramosum, C. innocuum, and C. clostridioforme) are often mis-identified in laboratories due to their Gram stain variability, lack of spores, and unusual colony morphology. The isolate in this case report was initially identified as another species of clostridia at a local laboratory before being definitively identified at the CDC. A study examining three rapid identification kits found that none could accurately identify this organism, suggesting that more complex biochemical and fermentation methods as well as gas-liquid chromatography are required for C. innocuum identification .
Accurate diagnosis in cases of systemic infection is paramount, since this species displays greater resistance to antibiotics compared to other clostridia. For instance, many C. innocuum isolates have resistance to vancomycin with MICs of 4–16 mcg/ml [9, 10]. Studies have shown that the resistance is intrinsic and related to the presence of two chromosomal genes allowing the synthesis of a peptidoglycan precursor with low vancomycin affinity [11, 12]. The presence of impaired susceptibility to vancomycin in a clostridial species should suggest that the isolate may be C. innocuum . C. innocuum may become selected for as a consequence of prior treatment with oral vancomycin, for example, in the setting of a prior C. difficile infection. In addition to vancomycin, C. innocuum isolates often have decreased susceptibility to cephalosporins, clindamycin, and quinolones . Antibiotics such as metronidazole and ampicillin-sulbactam are typically active against this organism . The MICs for newer agents, such as linezolid and daptomycin, have been reported as 2–4 mcg/ml and 2–8 mcg/ml, respectively .
The outcome of clostridial infections are variable and depend on both the clostridial species and host. Some have suggested that C. innocuum isolates may be contaminants or represent transient bacteremia since usually only one blood culture is positive . However, these cases often occur in the setting of immunosuppression and antibiotics are initiated immediately, given the potential for mortality, so the pathogenicity of C. innocuum in clinical specimens may be uncertain. As demonstrated by this review, severe C. innocuum infections have been well-described [1, 4, 7, 8]. In addition to bacteremia, these organisms may cause empyema, pylephlebitis, and pelvic abscesses [2, 3]. The survival of patients with an endovascular infection in this review was 46%; deaths were due to the infection and/or the underlying condition. Advanced age and malignancy may be associated with poor clinical outcome .
In summary, this is the first case reported of Clostridium innocuum bacteremia among an AIDS patient. Given the propensity of this infection to occur in immunocompromised hosts and the rising numbers of this patient population, clostridial infections may become more common. This case suggests a possible association between prior C. difficile infection treated with vancomycin and the subsequent development of C. innocuum infection. Clinicians should be aware of the difficulties identifying this organism and its intrinsic resistance to several common antibiotics including vancomycin.
Support for this work was provided by the Infectious Disease Clinical Research Program (IDCRP), Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, of which the TriService AIDS Clinical Consortium (TACC) is a component. The IDCRP is a DoD tri-service program executed through USUHS and the Henry M. Jackson Foundation for the Advancement of Military Medicine in collaboration with HHS/NIH/NIAID/DCR through Interagency Agreement HU0001-05-2-0011.
The opinions or ascertains contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Departments of the Army, Navy, or Air Force, or the Department of Defense. The authors have no commercial or other association that might pose a conflict of interest in this work.