Bloodstream Infection with Anaerobiospirillum succiniciproducens: A Potentially Lethal Infection

Abstract

Anaerobiospirillum succiniciproducens (A succiniciproducens), a spiral, Gram-negative anaerobic rod which is part of the normal intestinal flora of cats and dogs, has rarely been reported as a cause of bacteremia and diarrhea in humans, particularly in immunocompromised hosts. Although it can be associated with significant mortality, the full extent of its pathogenicity, clinical spectrum, and optimal therapy remain to be determined. We review the available literature on microbiology, clinical manifestations, and treatment options for Anaerobiospirillum infection.

Anaerobiospirillum succiniciproducens (A succiniciproducens) is a spiral, motile, Gram-negative anaerobic rod with bipolar tufts of flagella that was described for the first time by Davis et al in 1976.¹ It is part of the normal intestinal flora of cats and dogs² and has been reported as a rare cause of bacteremia^3,4 and diarrhea⁵ in humans, particularly in immunocompromised hosts. It may not respond to treatment with metronidazole. We recently reported the first known case of A succiniciproducens bloodstream infection (BSI) treated with oral levofloxacin.⁶ The full extent of its pathogenicity, clinical spectrum, and optimal therapy remain to be determined. We review the available literature on microbiology, clinical manifestations, and treatment options for Anaerobiospirillum infection.

Methods

Review of the Literature

All previous studies included in our literature review were found using a PubMed search (through January 2010) of the medical literature, applying the terms “Anaerobiospirillum” and “infection.” In addition, the references cited in these articles were examined to identify additional reports.

Results

We identified 56 cases of Anaerobiospirillum spp. infection that have been published to date.^2–5,7–24 The cases had a global distribution and 23 cases (41.1%) were identified in the United States (US), 21 cases (37.5%) in Europe, 5 cases (8.9%) in Asia, 4 cases (7.1%) in Oceania, 2 cases (3.6%) in Africa and 1 case (1.8%) in South America; all of the cases appear to have been epidemiologically unrelated. Five cases^{11,14,15,17,19} were excluded due to non-English language or not enough information, and 51 cases were included in our review.^{2–5,7–10,12–13,16,18,20–24} Twenty eight (54.9%) patients were male. The mean age was 42.6 years (range, 6 months-90 years). We identified 33 cases of BSI due to A succiniciproducens,^{2–4,7–10,12,13,16,18,20,21,23,24} 16 cases of diarrhea without associated bloodstream infections (BSI) due to Anaerobiospirillum thomasii (A. thomasii)^5,16 and 2 cases of diarrhea without associated BSI due to A succiniciproducens.^5,16

We further analyzed the 33 reported cases of BSI due to A succiniciproducens (Table 1). Nineteen (57.6%) patients were male and the mean age was 54.1 years (range, 11 months-90 years). An underlying disorder was present in 28 of 31 patients (90.3%); 11 (39.3%) had a history of chronic alcoholism, 10 (35.7%) had an underlying malignancy, 8 (28.6%) had a history and/or clinical evidence of atherosclerosis, and 4 (14.3%) patients had a history of recent surgery, including a colectomy, resection of squamous cell cancer of the neck, abdominal surgery, and endarterectomy. Three (10.7%) patients had liver disease, three (10.7%) had insulin-dependent diabetes, and three (10.7%) had documented poor dentition. Only three patients had documented exposure to animals. Two (7.1%) patients had undergone recent chemotherapy or splenectomy, and two patients had AIDS.^3,11

Table 1.

Description of 33 cases of bacteremia with Anaerobiospirillum succiniciproducens with available data^a

Author	Country	Age (yr)	Sex (M/F)	Underlying conditions	Symptoms	Susceptibility testing	Treatment	Outcome
Fadzilah et al7	Malaysia	17	M	Acute lymphoblastic leukaemia	Fever and diarrhea during a febrile neutropenic episode	Not available but the metronidazole disc used to screen for anaerobes showed no zone of inhibition.	Piperacillin-tazobactam, Imipenem (duration NR)	The patient improved only after therapy was switched to imipenem and vancomycin. He was discharged after a total hospital stay of 13 days
Mikami et al8	Japan	71	M	Liver cirrhosis and hepatocellular carcinoma	Diarrhea, fever	NA	NA	NA
Secchi et al9	Brazil	73	F	Diabetes mellitus type 2, atherosclerosis, impaired cardiac function, and a cerebrovascular accident	Fever, nausea, vomiting, sepsis, and diarrhea	Not done	Piperacillin tazobactam (8 days)	Died on day 27 postadmittance
Pienaar et al4	South Africa	25	F	Malignancy	Twelve hours after chemotherapy, she developed fever, chills, generalized myalgia, nonproductive cough, and abdominal cramps, followed by a single episode of loose stools	The MICs of the isolate were: amoxicillin-clavulanic acid, 2.0 mg/L; cefoxitin, 1.0 mg/L; clindamycin, 16 mg/L; erythromycin, 32 mg/L; imipenem, 0.06 mg/L; metronidazole, 16 mg/L; and penicillin, 0.5 mg/L. According to the NCCLS breakpoints for anaerobes, the isolate was susceptible to amoxicillin-clavulanic acid, cefoxitin, imipenem, and penicillin, intermediately resistant to metronidazole, and resistant to clindamycin. The organism did not produce b lactamase.	Amoxicillin-clavulanic acid (duration NR)	Recovered
Rudensky et al	Israel	11 months	F	No underlying conditions	2-day history of fever, irritability, vomiting and loss of appetite	Susceptible to amoxicillin/clavulanic acid and chloramphenicol, intermediately susceptible to amoxicillin, and resistant to penicillin, erythromycin, clindamycin and metronidazole.	Amoxicillin for 10 days	The child had a complete and uneventful recovery; follow-up blood cultures were not done
Tee et al3	Australia	53	M	Alcoholic liver disease	Fever(2-day hospital day)	Resistant to penicillin G, clindamycin and metronidazole but sensitive to chloramphenicol, imipenem, amoxicillin-clavulanate, and ticarcillin-clavulanate. Although there are no documented breakpoints for ciprofloxacin for anaerobic organisms, for all three isolates MICs were in the susceptible range for aerobic bacteria	No antibiotics	Became afebrile, and was discharged 2 days later
Tee et al3	Australia	48	M	AIDS, two weeks after chemotherapy for T-cell non-Hodgkin lymphoma	After 4 days in hospital he developed high fevers (up to 38.7°C), a productive cough, and diarrhea.	Resistant to clindamycin and metronidazole but sensitive to chloramphenicol, imipenem, amoxicillin-clavulanate, and ticarcillin-clavulanate. Although there are no documented breakpoints for ciprofloxacin for anaerobic organisms, for all three isolates MICs were in the susceptible range for aerobic bacteria	Ticarcillin-clavulanate	The patient continued to deteriorate and died 7 days later.
Tee et al3	Australia	57	M	History of non-Hodgkin lymphoma presented 12 days post chemotherapy splenectomy	3-day history of fever and night sweats, a 2-week history of malaise.	Resistant to clindamycin and metronidazole but sensitive to chloramphenicol, imipenem, amoxicillin-clavulanate, and ticarcillin-clavulanate. Although there are no documented breakpoints for ciprofloxacin for anaerobic organisms, for all three isolates MICs were in the susceptible range for aerobic bacteria.	Ticarcillin-clavulanate and gentamicin for 4 days and then orally with ciprofloxacin for 3 days	Rapid resolution of his symptoms
Goddard et al12	UK	63	F	Alcoholism, cirrhosis	Confusion	Sensitivities by disc diffusion showed sensitivity to cefuroxime, resistance to erythromycin and intermediate sensitivity to metronidazole. E-test (AB Biodisk, Solna, Sweden) MIC were: cefuroxime 0.19 μg/mL; cefotaxime O0.023 μg/ml; penicillin 0.38 μg/mL; metronidazole >32 μg/mL (resistant); clarithromycin 3 μg/mL; erythromycin 16 μg/mL	Cefuroxime and parenteral erythromycin	Despite therapy, her condition continued to deteriorate and she died 12 days after admission.
Marcus et al13	Africa	43	F	Chronic bronchitis. She kept two pet dogs indoors.	Malaise, headache, myalgia, and haemoptysis	Disk diffusion susceptibility tests showed susceptibility to chloramphenicol (0.5 mg/L), ciprofloxacin (1 mg/L), cefoxitin (0.5 mg/L), and ampicillin (2 mg/L). It was resistant to metronidazole (64 mg/L) and erythromycin (4 mg/L).	Ceftriaxone and chloramphenicol was prescribed and continued for 14 days.	The patient was extubated after 27 days of mechanical ventilation. She made an uneventful recovery and was discharged after a total of 42 days in hospital. On follow-up she developed a reactive polyarthritis.
Yuen et al18	Hong Kong	46	M	No underlying diseases, but his wound was contaminated by the seawater at a reclamation site where rubbish and sewage were disposed of	Fever, wound infection	Susceptible to cefamandole, cephalothin, gentamicin, chloramphenicol, and septrin and resistant to penicillin, metronidazdole, nali-dixic acid, and vancomycin.	Benzylpenicillin, metronidazole, cefamandole, and gentamicin were given for the next 14 days	Despite four debridments and continuing antibiotic therapy, the wound continued to have a purulent discharge, with signs of ischemia distal to the laceration. Finally, a below-elbow amputation was done, and the patient became afebrile.
McNeil et al20	USA	38	M	Alcoholism	Afebrile, nausea, vomiting	ND	Chloramphenicol	Recovered
McNeil et al20	USA	69	M	Prostate cancer, atherosclerosis	Fever	ND	Cefazolin, tobramycin cephalexin	Recovered
McNeil et al20	USA	48	F	Surgery	Afebrile	ND	None	Recovered
McNeil et al20	USA	54	M	Bowel cancer	Afebrile	ND	Tetracycline	Died
McNeil et al20	USA	87	F	Atherosclerosis	Afebrile, Nausea, hematemesis	ND	Penicillin G, tobramycin	Died
McNeil et al20	USA	59	M	Alcoholism, poor dentition	Afebrile, Jaundice	ND	Cefoxitin, penicillin G, gentamicin	Recovered
McNeil et al20	USA	72	M	Alcoholism, atherosclerosis, neck cancer, surgery	Hypothermia, Jaundice	ND	None	Died
McNeil et al20	USA	40	F	Diabetes	Fever, nausea, vomiting	ND	Erythromycin	Recovered
McNeil et al20	USA	90	F	Atherosclerosis	Afebrile, anorexia	ND	Tetracycline	Recovered
McNeil et al20	USA	65	M	Colon cancer, anemia	Afebrile	ND	None	Recovered
McNeil et al20	USA	55	M	Alcoholism, colon cancer, surgery	Fever, diarrhea, abdominal pain	ND	Tobramycin, penicillin G, clindamycin	Recovered
McNeil et al20	USA	66	F	Alcoholism	Afebrile rectal bleeding, ascites	ND	None	Recovered
McNeil et al20	USA	54	F	Alcoholism	Afebrile, diarrhea	Penicillin (MIC 8), cefoxitin (MIC 0.12), clindamycin (MIC 4), chloramphenicol (0.25) metronidazole (4), tetracycline (<0.06) ND: cephalothin vancomycin, ampicillin cefotaxime erythromycin (Dilution method)	Gentamicin, cefazolin	Died
McNeil et al20	USA	67	M	Alcoholism, atherosclerosis	Afebrile, melena, jaundice		Gentamicin cefoperazone	Died
McNeil et al20	USA	30	F	Diabetes	Afebrile, nausea	Penicillin (MIC 1), cephalothin (MIC 8) cefoxitin (MIC <0.5), cefotaxime <0.5 clindamycin (MIC >16), erythromycin 16, chloramphenicol (<0.5) metronidazole (4–32), tetracycline (4) ND: vancomycin, ampicillin cefotaxime erythromycin (Dilution MIC method)	Ampicillin	Recovered
McNeil et al20	USA	39	F	Atherosclerosis, diabetes	Fever, abdominal pain, diarrhea		None	Died
McNeil et al20	USA	79	F	None	Fever, nausea, vomiting, diarrhea		None	Recovered
Park et al21	USA	30	M	Poor dentition	Afebrile vomiting, abdominal pain, diarrhea	S Penicillin (MIC 0.5), cephalothin (MIC 2) cefoxitin (MIC <0.5), cefotaxime (MIC <0.5) clindamycin (MIC 16), erythromycin (MIC 4), chloramphenicol (<0.5) metronidazole (4), tetracycline (2) ND: vancomycin, ampicillin (Dilution MIC method)	Penicillin V, trimethoprim-sulfamethoxaz	Recovered
Park et al21	USA	87	M	Poor dentition	Fever, nausea, vomiting	S Penicillin (MIC 2), cephalothin (MIC 8) cefoxitin (MIC <0.5), cefotaxime (MIC <0.5) clindamycin (MIC >16), erythromycin (MIC 16), chloramphenicol (<0.5) metronidazole (8), tetracycline (4) ND: vancomycin, ampicillin (Dilution MIC method)	Ampicillin, cefamandole cefoperazone	Recovered
Shlaes et al23	USA	34	M	Alcoholism	Fever nausea, vomiting, abdominal pain, ascites	R to Penicillin, vancomycin ND: cefoxitin, cefotaxime, clindamycin, metronidazole S to cephalothin, erythromycin, chloramphenicol, tetracycline, ampicillin (disk susceptibility)	Gentamicin, erythromycin	After an initial response to antimicrobial therapy, this patient suffered a relapse on day 12, with fever, severe myalgia, and evidence of sacroileitis. These symptoms responded to indomethacin, and the infection was ultimately cured.
Shlaes et al23	USA	52	M	Alcoholism, cirrhosis, postsplenectomy. This patient recalled having been bitten by cat fleas be-fore his illness but reported no direct exposure to dogs.	Fever, hematemesis, rectal bleeding, ascites	R to Penicillin, vancomycin ND: cefoxitin, cefotaxime, clindamycin, metronidazole S to cephalothin, erythromycin, chloramphenicol, tetracycline, ampicillin (disk susceptibility)	Ampicillin, tobramycin then chloramphenicol	Recovered
Rifkin and Opdyke24	USA	75	M	Surgery (sepsis after carotid endarterectomy), atherosclerosis	Afebrile. Decrese in vision	R to Penicillin, erythromycin, ampicillin. ND: metronidazole, cefoxitin, cefotaxime, vancomycin. S to cephalothin, clindamycin, chloramphenicol, tetracycline (disk susceptibility)	Gentamicin, clindamycin	Died

^aND, not done; R, resistant; S, sensitive; NCCLS, National Committee on Clinical Laboratory Standards; MICs, minimum inhibitory concentrations; AIDS, acquired immunodeficiency syndrome.

Prominent clinical features included gastrointestinal tract signs and symptoms in 17 (70.8%) of 24 symptomatic patients (presence of fever or gastrointestinal symptoms). Gastrointestinal signs and symptoms included diarrhea in 11 (64.7%) patients, vomiting in 11 (64.7%), nausea in 10 (58.8%), bleeding in 8 (47%), and abdominal pain in 2 (11.8%) patients.

Fever >38 Celsius was documented in 17 (60.7%) of 33 patients with BSI. Fifteen (45.5%) patients were afebrile, one patient (3%) was hypothermic, and eight patients (24.2%) were asymptomatic (absence of fever or any gastrointestinal symptoms). Interestingly, polymicrobial bacteremia was reported in six cases (18.2%)^9,20 and more specifically, pathogens that were isolated simultaneously with A succiniciproducens included Streptococcus pneumoniae,²⁰ Staphylococcus aureus,⁹ Staphylococcus spp,²⁰ Escherichia coli,²⁰ Proteus spp,²⁰ Peptococcus sp,²⁰ and Propionibacterium acnes.²⁰ Data on follow up blood cultures were not available in most case reports reviewed, and thus we could not determine the duration of A succinoproducens BSI.

The identity of A succinoproducens was confirmed with a 16S rRNA sequencing test in six cases (18.2%).^3,7–9 Disk diffusion, microdilution, and E-test antimicrobial susceptibility testing on blood-culture isolates were performed in seven,^{3,10,12,13,18,23,24} three,^4,20,21 and one¹² studies, respectively, and showed that A succinoproducens isolates were susceptible to amoxicillin,^{10,12,13,23,24} amoxicillin–clavulanic acid,^3,4,10,12,13 ticarcillin-clavulanate,^3,12 cephalothin,^{18,20,21,23,24} cefamandole,¹⁸ cefuroxime,¹² cefoxitin,^4,20,21 cefotaxime,^12,13,20,21 imipenem,^3,4 chloramphenicol,^{3,10,13,18,20,21,23,24} tetracycline,^20,21,23,24 gentamicin,¹⁸ trimethoprim-sulfamethoxazole,¹⁸ and ciprofloxacin.^3,13 A succinoproducens isolates were resistant to vancomycin^18,23 and nalidixic acid,¹⁸ tended to be resistant to metronidazole,^{3,4,10,12,13,18,21} clindamycin,^{3,4,10,20,21,24} and erythromycin^{3,4,10,12,13,20,21,23,24} and had variable susceptibility to penicillin.^{3,4,10,12,18,20,21,23,24} In Table 2 we summarize the % susceptibility of A succinoproducens isolates to each class of antibiotics based on available data. However, in most studies susceptibility of A succinoproducens to different antibiotics was either not performed or not reported. In the few studies in which susceptibility testing was performed, no detailed data on susceptibility for all different classes of antibiotics were reported. The A succinoproducens isolate in our case was susceptible to the following antibiotics at minimum inhibitory concentrations (MICs): mero-penem (≤0.25 μg/mL), metronidazole (8 μg/mL), penicillin (0.5 μg/mL), piperacillin/tazobactam (≤8), levofloxacin (MIC: 0.5 μg/mL), and resistant to clindamycin (>16 μg/mL).

Table 2.

Percent (%) susceptibility of reported isolates of A succinoproducens to different antibiotics^a

Antibiotic	No. isolates	Percent of susceptibility, n (%)	Methods used (no. isolates)	References
Penicillin	12	41.7 (5/12)	Disk diffusion (7), dilution method (4), E-test (1)	3, 4, 10, 12, 18, 20, 21, 23, 24
Amoxicillin	6	83.3 (5/6)	Disk diffusion (5), E-test (1)	10, 12, 13, 23, 24
Amoxicillin-clavulanate	7	100 (7/7)	Disk diffusion (5), dilution methods (1), E-test (1)	3, 4, 10, 12, 13
Ticarcillin-clavulanate	4	100 (4/4)	Disk diffusion (3), E-test (1)	3, 12
Cephalothin	7	71.4 (5/7)	Disk diffusion (4), dilution methods (3)	18, 20, 21, 23, 24
Cefamandole	1	100 (1/1)	Disk diffusion (1)	18
Cefuroxime	1	100 (1/1)	E-test (1)	12
Cefoxitin	5	100 (5/5)	Dilution methods (5)	4, 20, 21
Cefotaxime	5	100 (5/5)	Disk diffusion (1), dilution methods (3), E-test (1)	12, 13, 20, 21
Imipenem	4	100 (4/4)	Disk diffusion (3), dilution methods (1)	3, 4
Chloramphenicol	13	100 (13/13)	Disk diffusion (9), dilution methods (4)	3, 10, 13, 18, 20, 21, 23, 24
Metronidazole	12	25 (3/12)	Disk diffusion (6), dilution methods (5), E-test (1)	3, 4, 10, 12, 13, 18, 21
Clindamycin	10	10 (1/10)	Disk diffusion (5), dilution methods (5)	3, 4, 10, 20, 21, 24
Erythromycin	11	27.3 (3/11)	Disk diffusion (6), dilution methods (4), E-test (1)	3, 4, 10, 12, 13, 20, 21, 23, 24
Tetracycline	7	71.4 (5/7)	Disk diffusion (3), dilution methods (4)	20, 21, 23, 24
Gentamicin	1	100 (1/1)	Disk diffusion (1)	18
TMP-SMZ	1	100 (1/1)	Disk diffusion (1)	18
Ciprofloxacin	4	100 (4/4)	Disk diffusion (4)	3, 13
Nalidixic acid	1	0 (0/1)	Disk diffusion (1)	18
Vancomycin	3	0 (3/3)	Disk diffusion (3)	18, 23

^aTMP-SMZ, trimethoprim-sulfamethoxazole.

Antibiotics that have been used for treatment of this organism (see Table 1) include penicillin in eight cases (25%),^18,20,21 gentamicin in six cases (18.8%),^18,20,23,24 tobramycin in five cases (15.6%),^20,23 amoxicillin in four cases (12.5%),^{10,20–21,23} erythromycin in three cases (9.4%),^12,20,23 chloramphenicol in three cases (9.4%),^13,20,23 piperacillin–tazobactam in two cases (6.3%),^7,9 ticarcillin-clavulanic acid in two cases (6.3%),³ cefazolin in two cases (6.3%),²⁰ cefoperazone in two cases (6.3%),^20,21 tetracycline in two cases (6.3%),²⁰ and clindamycin in two cases (6.3%).^20,24 Amoxicillin-clavulanate,⁴ cefamanzole,²¹ imipenem,⁷ cefoxitin,²⁰ cefuroxime,¹² ceftriaxone,¹³ metronidazole,¹⁸ and bactrim²¹ have also been used in isolated cases. Combination of antimicrobials was used in 11 cases (34.4%),^{12,13,18,20,21} including combinations of β-lactam (penicillin or cephalosporin) plus aminoglycoside in 7 cases,^12,18,20,21 ceftriaxone and chloramphenicol,¹³ cefuroxime and erythromycin,¹² penicillin V, and trimethoprim-sulfamethoxazole.²¹ In all of these cases, treatment was empiric and A succinoproducens was only identified later during the hospitalization. In addition, antimicrobial susceptibility testing was not performed in most cases. The duration of antimicrobial therapy was reported in only five cases and varied between 7 and 14 days.^3,9,10,13,18

In one case the clinical outcome of A succinoproducens BSI was not reported.⁸ The overall mortality from cases of A succinoproducens BSI was 31.3% and 10 patients died.^3,9,12,23 These patients had more than two comorbidities, and in 3/10 (30%) of these cases there was concurrent BSI with another pathogen, including Staphylococcus aureus,⁹ Streptococcus pneumoniae,¹² and Escherischia coli.²⁰ Twenty patients (66.7%) recovered without any sequelae.^{3,4,7,10,18,20–21,23} Two patients (6.3%) recovered but developed post-infectious reactive arthritis.^13,23 Although 25 patients (78.2%) received antimicrobial therapy, its effect on the outcome of the infection was unclear. Five patients (15.2%) recovered without any treatment.³ One patient recovered despite inappropriate antimicrobial therapy (erythromycin).

Discussion

Anaerobiospirillum spp is a group of spiral, motile, Gram-negative, anaerobic rods that have been isolated from the feces of mammals including cats, dogs, and humans.^1,5 There are two known Anaerobiospirillum species that infect humans: A succiniciproducens causes both bloodstream infections^{3,10–14,17–20,24} and diarrhea,⁵ and A. thomasii has only been implicated as a cause of diarrhea.¹⁶ A succiniciproducens is more likely to cause BSI than diarrhea and has been reported in the US, Europe, Africa, and Asia, suggesting a global distribution.^{5,13,15,18,19,21–24} Most patients with diarrheal disease did not have an underlying disorder, and most patients recovered from the infection.^2,5 In contrast, almost all reported cases of BSI have been in patients with an underlying illness. The first report of BSI caused by A succiniciproducens was described in 1981 by Rifkin and Opdyke.²⁴ McNeil et al,²⁰ reviewed all cases of BSI caused by anaerobic Gram-negative bacilli in the US that occurred between 1975 and 1986. They identified 22 cases of BSI due to A succiniciproducens and observed that most of these patients had some degree of immunosuppression, but the pathogenesis of this infection remains unclear.

Pathogenesis of Anaerobiospirillum Infection

Anaerobiospirillum species are part of the normal intestinal flora of cats and dogs, but apparently not of humans.^5,25–27 In one study, A succiniciproducens was isolated in 7.4% of animals.²⁶ Based on limited data from case reports,^2,18 it has been suggested that Anaerobiospirillum species are zoonotic bacteria transmitted to humans from animals, and are underdiagnosed because human stool samples are not routinely screened for these organisms.^2,5 Although Anaerobiospirillum spp. do not appear to be part of the normal intestinal flora of humans, A. thomasii and A succiniciproducens have been isolated from the stool of patients with diarrhea.^5,16 However, in one study of 527 fecal samples from asymptomatic individuals, A succiniciproducens was not detected in any of these samples.² Previous reports have suggested that the primary portal of entry in patients with BSI caused by this microorganism appears to be the gastrointestinal tract.^5,20 Waterborne transmission was suggested in one patient with wound infection who was exposed to sea water.¹⁸ Human to human transmission has not been reported.²²

Most patients with A succiniciproducens BSI had underlying disorders, such as chronic alcoholism,^{3,12,14,19,20} atherosclerosis,^20,24 malignancies,^3,17,19,20 recent surgery,²⁰ diabetes mellitus,^17,20 dental caries,²⁰ and AIDS.^3,11 We found that reported underlying disorders in decreasing order of frequency were alcoholism, malignancy, atherosclerosis, surgery, diabetes mellitus, and poor dentition. Chronic alcoholism is known to be associated with increased risk of developing BSI with anaerobic microorganisms.^{3,12,14,19,20} Poor nutritional status, disruption of the integrity of the gastrointestinal mucosa, presence of ascites (27.3% of alcoholic patients in our study) that may be associated with increased translocation of bacteria (we found six cases of polymicrobial BSI^9,20), and alterations of the host immune defense system may be important mechanisms in these patients. Whether a defect of the gastrointestinal mucosal barrier leads to invasion by A succiniciproducens, or whether other unknown cofactors are needed for it to gain access to the patient’s bloodstream is yet to be determined.

Microbiology

Demonstration of polar tufts of flagella using electron microscopy on a stained smear preparation is crucial in differentiating Anaerobiospirillum from closely related genera.^{3,10,11,24,28} Anaerobiospirillum spp may be mistakenly identified as Campylobacter spp due to its similar shape on Gram staining and positive motility. Anaerobiospirillum spp are oxidase and catalase negative, demonstrate corkscrew-like motility, and have bipolar tufts of flagella, whereas Campylobacter spp are oxidase and catalase positive, display darting motility and have a single flagellum on one or both poles.^11,20

Biochemical tests with commercial kits are also being used for the identification of this organism. Useful biochemical markers for Anaerobiospirillum spp. include the following: negative catalase, oxidase, indol, and nitrate reduction.³ According to previous reports, A succiniciproducens and A. thomasii can be differentiated by biochemical tests with carbohydrate fermentations and by the enzyme profiles obtained with API-ZYM strips, notably, the absence of β-galactosidase and α-glucosidase activities.¹⁶ A succiniciproducens is β-galactosidase and lactose positive.^{1,3,5,14,16,18,24}

Determination of the 16S rRNA gene by polymerase chain reaction amplification and sequencing, however, is the most accurate method for identification and classification of Anaerobiospirillum spp.³

Ordering of fecal cultures for inpatients staying for long periods in the hospital is neither common nor considered adequate.²⁹ Any attempt to isolate uncommon pathogens from fecal samples should be discussed with microbiology specialists, since these organisms usually will not grow on media commonly used to screen for specific enteropathogenic organisms.

Antimicrobial Susceptibility

Owing to the rare reports of BSI caused by this organism, the optimal antimicrobial treatment for A succiniciproducens still remains to be determined. Differentiation from Campylobacter spp is important from epidemiologic and treatment perspectives. Unlike Campylobacter spp, A succiniciproducens is usually resistant to erythromycin. In addition, it is most important to identify A succiniciproducens, in that it is often resistant to many antibiotics normally prescribed for anaerobic infections, such as clindamycin and metronidazole.^3,4,18,20 This organism is reported to be susceptible to amoxacillin-clavulanic acid, cephalosporins, and chloramphenicol, and resistant to vancomycin and nalidixic acid.^4,12,20,30 Susceptibilities to penicillin G, ampicillin, erythromycin, clindamycin, and metronidazole are variable.³ Although we found that only 41.7% of the reported isolates with available susceptibility data were susceptible to penicillin because high levels of penicillin are achievable in blood, infection with isolates for which MICs may be elevated (intermediate susceptibility) may be treatable. Although there are no documented breakpoints for fluoroquinolones for anaerobic organisms, seven isolate MICs were in the susceptible range for aerobic bacteria and Anaerobiosprillum was reported to be susceptible to quinolones in vitro.^3,13,31 In one study, three isolates of A succiniciproducens were sensitive to gemifloxacin and trovafloxacin,³¹ whereas four isolates of A succiniciproducens have been described to be susceptible to ciprofloxacin.^3,13 However, the effect of antimicrobial treatment on the outcome of the infection remains unclear.²⁰

Clinical Manifestations

A succiniciproducens can cause both BSI^{3,10–14,17–20,24} and diarrhea.^5,16 Many of these patients, however, are afebrile and asymptomatic. In the majority of these patients, bacteremia was preceded and/or accompanied by gastrointestinal signs and symptoms (ie, nausea, vomiting, abdominal pain, and gastrointestinal tract hemorrhage), a significant febrile reaction, and a prominent leukocytosis. It is important to note that postinfection sequelae, notably arthritis, can also occur in some patients.^13,23,30

Treatment

The optimal treatment for A succiniciproducens is not yet known, with some reported patients dying despite treatment with antibiotics to which the bacteria showed in vitro susceptibility, and some recovering without any antimicrobial treatment.^3,20 Although most of the patients had received antimicrobial therapy, its effect on clinical outcome was unknown. Several untreated patients recovered, while several treated patients died. We found a significant mortality rate for this infection (31.3%). Six of these patients presented with polymicrobial BSI and died despite institution of appropriate antimicrobial therapy. On the other hand, five patients (15.2%) recovered without any treatment.^3,12 Thus, further studies are needed to define the role of antimicrobial threpapy in BSI with A succiniciproducens.

Clinicians should be aware of therapeutic options for treatment of A succiniciproducens infection, as this organism has been associated with significant mortality in certain cases. It is possible to treat patients with A succiniciproducens with oral fluoroquinolones, especially if they are afebrile and asymptomatic.¹² Fluoroquinolones can be useful antimicrobial agents in these cases, especially in the setting of allergy to penicillin and potential resistance of this anaerobe to clindamycin and metronidazole, which are normally common therapeutic options for anaerobic infections.

Limitations

There are limitations in this review of the literature. A lack of detailed exposure histories for some patients may have resulted in underreporting of patients’ exposures. Variations in referral practices for these unusual isolates and differences in the type of commercial blood culture identification systems may have affected the frequency of isolation of A succiniciproducens from patients’ blood cultures. In addition, the apparent fastidiousness of the isolates prevented the determination of their antimicrobial susceptibilities in many of the reported cases by use of a standardized method. Finally, certain information such as duration of treatment was not available in many of the reported cases of A succiniciproducens reviewed herein.

Conclusion

A succiniciproducens may be a significant pathogenic anaerobe that is underreported. A high index of suspicion on the part of microbiologists and clinicians may be an important factor in the early recognition of bacteremia in patients with infections due to this organism. The increased awareness of the importance of this unusual agent as the cause of human disease will help us further understand its epidemiology and treatment.

Key Points.

• Anaerobiospirillum succiniciproducens (A succiniciproducens) may be a significant pathogenic anaerobe that is underreported. However, the full extent of the pathogenicity, clinical spectrum, and optimal therapy of A succiniciproducens infections remains to be determined.

• We summarize the scientific evidence on the pathogenesis, clinical manifestations, treatment, and outcome of A succiniciproducens bloodstream infections. We also summarize detailed data on the antimicrobial susceptibility of A succiniciproducens.

• Clinicians should be aware of therapeutic options for treatment of A succiniciproducens infection, as this organism has been associated with significant mortality (31%).