Leptotrichia Bacteremia in Patients Receiving High-Dose Chemotherapy

Abstract

Leptotrichia spp. are anaerobic, pencil-shaped, Gram-negative rods that are part of the normal oral and intestinal human flora. Although not typically considered pathogenic, invasive Leptotrichia infections have been reported in immunosuppressed patients. A perceived rise in the identification of Leptotrichia spp. at our institution prompted a retrospective evaluation of these infections. Laboratory and clinical records were reviewed to identify Leptotrichia culture-positive patients. Over a 5-year period, 68 Leptotrichia-positive specimens were identified. Of these, 21% (14/68) were identified in original samples submitted from 13 different patients at our institution, and the remainder (79% [54/68]) were unknown isolates referred from outside hospitals for molecular identification. All in-house Leptotrichia were identified from blood cultures. Only 64% (9/14) of these grew on solid media, and 5 were a part of polymicrobial bacteremias containing other enteric pathogens. All local patients were receiving chemotherapy and a majority received hematopoietic stem cell transplant (HSCT) (11/13). All had neutropenic fever with symptoms of mucositis and/or enteritis. Most of the HSCT patients (73% [8/11]) were autologous recipients hospitalized after recent highdose chemotherapy for multiple myeloma. L. hongkongensis, a novel species, was found in the majority of myeloma cases (63% [5/8]). In conclusion, we suggest that Leptotrichia spp. may be an underappreciated cause of bacteremia, particularly in multiple myeloma patients receiving cytotoxic chemotherapy for autologous HSCT. In our cohort, these infections were associated with neutropenic fever from an enteric source, and most isolates remained sensitive to standard antibiotics. H igh-dose chemotherapy followed by hematopoietic stem-cell transplantation (HSCT), is a well-established treatment modality for a variety of hematologic malignancies; however, infectious complications remain a major barrier to the overall success of this procedure. HSCT recipients are at particularly high risk for the development of invasive bacterial infections as a result of regimen-related neutropenia and cytotoxic damage to the oral and gastrointestinal mucosa. Mucositis severity, specifically, is an independent predictor of anaerobic bloodstream infection (BSI) following HSCT (11).Leptotrichia spp. are fastidious anaerobic, pencil-shaped, Gram-negative rods that reside in the mouths, intestines, and female genital tracts of humans (20). Traditionally considered to be nonpathogenic, Leptotrichia species have occasionally been reported to cause invasive disease in HSCT patients and other immunocompromised hosts (6, 14, 18). The overall incidence of Leptotrichia infections in at-risk patient populations, however, may be underestimated. These organisms are notoriously difficult to recover from blood culture and may retain crystal violet, which can lead to their misidentification as Gram-positive rods. Commercially available phenotypic identification systems also have problems classifying...

Leptotrichia species in human infections II

“…L . buccalis was for centuries the only known Leptotrichia species, but new species have now been formally accepted, which include L. goodfellowii , L. hofstadii , L. shahii , L. trevisanii , and L. wadei (Figure 1) [2,4,5] and L. hongkongensis [6]. As with other members of the oral commensal microbiota, Leptotrichia species are also associated with periodontal diseases and oral cavity abscesses [5,7,8], typically as opportunistic infections.…”

“…Leptotrichia species can cause opportunistic infections that lead to bacteremia in neutropenic patients with oral mucosal injuries [2,5] and bacteremia due to L. trevisanii after an allogeneic bone-marrow transplant [13]. Although systemic infections involving Leptotrichia species are infrequent, severe infections have been reported in immunocompromised patients [2,4,7,9,10,13–19].

Figure 1.A phylogenetic tree obtained from the MEGA (www.megasoftware.net) program based on only sequences >800 bp by neighbor joining after ClustalW alignment.

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“…Since previous reviews [2,3], Leptotrichia species have been reported in >124 cases [4,7,16,18–69,87–93], whereby 30 cases involved L. buccalis [4,8,15,21,34,52,56,70–79,87], 24 cases L. wadei [4,20,24,34,37,42,48,56,67,80,81,90,93], 16 cases L. trevisanii [4,5,9,10,13,14,17,37,87], 14 cases L. hofstadii [34,40,49,56,81–84,93], 10 cases L. goodfellowii [4,11,12,21,56,74,85,87], eight cases L. hongkongensis [4,6,18,45,47,56], and five L. shahii [34,56,86]. L. trevisanii and L. wadei bacteremia are extremely rare; clinicians should consider these species in cases involving immunocompromised patients with oral lesions [4,5,13,17,87]. The aim of the present review is to update the knowledge on the genus Leptotrichia as given in previous reports, adding information published after 2008 [2,3].…”

“…It has also been recovered from root canals of patients with or without other oral diseases, tissue fluids and subgingival plaque samples, and exudate with cellulitis after a dog bite (Table 2) [8,52,72–74,77,90]. Furthermore, it has been recovered from the blood and amniotic fluid of a female patient and from the amniotic fluid of an afebrile pregnant woman with acute chorioamnionitis [4,78] (Table 2). It has also been detected in saliva, on the mucosal surface of patients with removable partial dentures, in peri-implant crevicular fluids [34,76,79], and in biofilms (Table 2) [75].…”

“…It has also been isolated from the blood of an amniotic fluid patient with a wound and respiratory difficulties [4], from a wound exudate of a healthy person with cellulitis after a dog bite [74], from saliva, plaque, and the mucosal surface of caries-active patients and diabetic smokers [56,90], and from the blood of patients with heart failure, diabetes, bladder cancer, pulmonary edema, and bronchopneumonia [11]. L. goodfellowii has been recovered from an immunocompetent endocarditis patient with bioprosthetic pulmonic valve and an aortic valve homograft suffering from fever and chronic night sweats (diaphoretic) (Table 2) [12].…”