J Med Cases

Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc

Journal website https://www.journalmc.org

Case Report

Volume 13, Number 5, May 2022, pages 212-218

Clostridium tertium Bacteremia: A Marker of an Underlying Perforated Colonic Diverticular Disease in a Non-Neutropenic Patient With COVID-19

Figure 1. Axial images of a contrast-enhanced abdomen and pelvis CT scan revealed (a) extensive free intraperitoneal gas (vertical red arrows) and (b) a thickened sigmoid colon wall (horizontal red arrow) and focal pelvic fluids collection (red star). CT: computed tomography.

**Table 1.** Pertinent Laboratory Results on Admission
Blood test	Result	Reference range
White cells count (WCC)	15,000/mm³	4,000 - 11,000/mm³
Hemoglobin	12.5 g/dL	11.0 - 13.0 g/dL
Platelets	390,000/mm³	150,000 - 500,000/mm³
C-reactive protein (CRP)	72 mg/dL	1 - 7 mg/dL
Serum creatinine	1.7 mg/dL	0.6 - 1.1 mg/dL
Serum sodium	132 mmol/L	133 - 144 mmol/L
Serum potassium	3.2 mmol/L	3.6 - 5.0 mmol/L
Serum magnesium	1.4 mmol/L	2.2 - 2.8 mmol/L
Serum lactate	3.1 mmol/L	0.5 - 2.2 mmol/L
Serum glucose (point-of-care, POCG)	350 mg/dL	70 - 110 mg/dL
Hemoglobin A1c	9.5%	< 5.7%
Serum albumin	3.1 g/dL	3.6 - 5.0 g/dL

Table 1. Pertinent Laboratory Results on Admission

Blood test

Result

Reference range

White cells count (WCC)

15,000/mm³

4,000 - 11,000/mm³

Hemoglobin

12.5 g/dL

11.0 - 13.0 g/dL

Platelets

390,000/mm³

150,000 - 500,000/mm³

C-reactive protein (CRP)

72 mg/dL

1 - 7 mg/dL

Serum creatinine

1.7 mg/dL

0.6 - 1.1 mg/dL

Serum sodium

132 mmol/L

133 - 144 mmol/L

Serum potassium

3.2 mmol/L

3.6 - 5.0 mmol/L

Serum magnesium

1.4 mmol/L

2.2 - 2.8 mmol/L

Serum lactate

3.1 mmol/L

0.5 - 2.2 mmol/L

Serum glucose (point-of-care, POCG)

350 mg/dL

70 - 110 mg/dL

Hemoglobin A1c

9.5%

< 5.7%

Serum albumin

3.1 g/dL

3.6 - 5.0 g/dL

**Table 2.** Summary of the Reported Cases of *C. tertium* Bacteremia as per Literature Review 1990 - 2022 (Including the Presented Case)
Authors/publication year	Age (years)/gender	Clinical presentation	Possible risk factors	Subspeciality testing results (if available)/antibiotics instituted to treat C. tertium
CT: computed tomography; C. tertium: Clostridium tertium; COVID-19: coronavirus disease 2019; IBD: inflammatory bowel disease; CD: Crohn’s disease; UC: ulcerative colitis.
Shah et al, 2016 [1]	82/female	Neutropenic fevers/abdominal pain and diarrhea. CT chest with ground glass opacities	Acute myeloid leukemia (AML) on chemotherapy	No susceptibility testing available. Infection was treated with vancomycin, piperacillin-tazobactam, and ciprofloxacin.
	36/female	Neutropenic fevers/vomiting and diarrhea	AML on chemotherapy	Susceptible to meropenem, piperacillin-tazobactam, penicillin, and metronidazole.
	42/female	Neutropenic fevers/shortness of breath and cough with a nodular infiltrate on chest CT	AML on chemotherapy	Susceptibility results were only provided to metronidazole, the patient was treated empirically with piperacillin-tazobactam and then a 2-week course of clindamycin.
	55/male	Neutropenic fevers/lower abdominal pain and diarrhea	Myelodysplastic syndrome (MDS) on chemotherapy	No subspeciality testing available. Initially treated with cefepime, followed by vancomycin and piperacillin-tazobactam.
	60/male	Neutropenic fevers/shortness of breath and cough and a new perihilar infiltrate on chest X-rays	AML on chemotherapy	No susceptibility testing available. Initially treated with cefepime, followed by a 2-week course of vancomycin and metronidazole.
	69/male	Neutropenic fevers with ground-glass opacities on chest CT imaging	MDS on chemotherapy	No susceptibility testing available. Initially treated with vancomycin and cefepime followed by piperacillin-tazobactam for 2 weeks.
	60/male	Neutropenic fevers/fatigue	AML on chemotherapy	No susceptibility testing available. Initially treated with ciprofloxacin, then switched to vancomycin and cefepime with cultures results.
Miller et al, 2001 [2]	28/male	Abdominal pain, vomiting, and watery diarrhea. CT abdomen with Crohn’s features. Colonoscopy and biopsy confirmed CD. Blood cultures grew C. tertium	CD	No susceptibility testing available. Empirically treated with ciprofloxacin and clindamycin.
Miller et al, 2001 [2]	A case series of 32 patients including the above one [2]; 22 patients were males; age ranged widely from 16 to 75 years; 29 patients were neutropenic secondary to chemotherapy. Three non-neutropenic patients were as follows: one had spontaneous bacterial peritonitis (SBP) associated with alcoholic liver cirrhosis, one with CD, and the last one with systemic lupus erythematosus (SLE) treated with high-dose steroids.
Steyaert et al, 1999 [3]	65/male	Neutropenic fevers/abdominal pain and diarrhea	AML on chemotherapy	Resistant to ceftazidime, cefepime, and clindamycin; intermediately resistant to penicillin; and susceptible to metronidazole, and vancomycin. Initially treated with ceftazidime and amikacin that were switched to vancomycin following sensitivity results.
	55/male	Neutropenic fevers/abdominal pain and diarrhea	AML on chemotherapy	Resistant to ceftazidime, cefepime, and clindamycin; intermediately resistant to penicillin; and susceptible to metronidazole, quinolones, and vancomycin. He was treated with vancomycin.
Wazir et al, 2019 [4]	62/male	Fatigue and high-grade fevers in a patient with end-stage liver disease. Ascitic fluid analysis revealed SBP. Blood cultures grew C. tertium	Alcoholic liver cirrhosis	Susceptible to meropenem, metronidazole, and penicillin. Initial empiric treatment with meropenem and vancomycin then targeted meropenem therapy for 9 days with clearance of C. tertium bacteremia.
Sutton et al, 2017 [5]	60/male	Worsening abdominal pain and fevers in the setting of chronic liver disease. Ascitic fluids culture isolated C. tertium	Alcoholic liver cirrhosis	Susceptible to meropenem, ciprofloxacin, clindamycin, and vancomycin. Initial empiric treatment with vancomycin and meropenem, then the latter was switched to ciprofloxacin and metronidazole. Repeat cultures were negative.
Chalhoub et al, 2016 [6]	54/female	Pancolitis progressed to septic shock with acute respiratory distress syndrome (ARDS). Serial blood cultures grew C. tertium	Colitis without evidence of IBD. Probable intestinal mucosal injury triggering C. tertium translocation	Susceptible to penicillin and vancomycin, resistant to clindamycin. Initially treated imipenem, vancomycin, and ciprofloxacin, the latter switched to ampicillin. The three-antibiotics regime was continued for 3 weeks with clearance of infection.
Gosbell et al, 1996 [7]	19/female	Recurrent neutropenic fevers	Acute lymphoblastic leukemia (ALL) on chemotherapy	Susceptible to penicillin, metronidazole, and vancomycin.
	57/female	Vomiting and diarrhea in a patient with a known history of UC	UC	No susceptibility testing available. C. tertium was isolated in the setting of polymicrobial isolates.
Coleman et al, 1993 [8]	15/female	Neutropenic fevers/abdominal pain and diarrhea. CT abdomen showing enterocolitis of the cecum and right colon	ALL on chemotherapy	No susceptibility testing available. Initially treated with ceftazidime, metronidazole, and gentamicin regime switched to ciprofloxacin and vancomycin when cultures grew C. tertium. Operative intervention with right hemicolectomy was indicated to control sepsis.
Tappe et al, 2004 [9]	51/female	Postoperative fever progressed to septic shock in the setting of ileus post-laparotomy and adhesiolysis	Paralytic ileus with probable mucosal injury secondary to ileus inducing C. tertium translocation	Susceptible to meropenem, imipenem, vancomycin, linezolid, and piperacillin-tazobactam, and resistant to penicillin, cefotaxime, clindamycin, and co-trimoxazole.
Milano et al, 2019 [10]	43/male	High-grade fevers due to a giant hepatic abscess 4 weeks post-appendectomy for a perforated appendix requiring radiology-guided drainage of the abscess	Perforated appendix with polymicrobial peritonitis and bacterial translocation and the recent use of broad-spectrum antibiotics	No susceptibility testing available. C. tertium was isolated in gram-negative polymicrobial blood cultures and the drained hepatic abscess substance. He was treated with radiologically guided hepatic abscess drainage conjugated with piperacillin-tazobactam.
You et al, 2015 [11]	44/female	Acute bronchopneumonia and C. tertium bacteremia identification of using 16S rRNA sequencing	Suicidal ingestion of glyphosate	Susceptible to penicillin, piperacillin/tazobactam, amoxicillin/clavulanic acid, cephalothin, cefoxitin, imipenem, and vancomycin, but resistance to cefotaxime, ceftazidime, cefepime, gentamicin, clindamycin, and metronidazole.
Ray et al, 2003 [12]	58/male	Necrotizing fasciitis of distal lower extremity requiring fasciotomy	History of non-Hodgkin lymphoma status post-chemotherapy 6 months prior to presentation. Alcoholic liver disease	No susceptibility testing available. The patient was treated with imipenem, vancomycin, and metronidazole.
	40/male	Necrotizing fasciitis of proximal lower extremity requiring extensive fasciotomy	Motor vehicle accident with multiple lower extremities and abdominal injuries	Susceptible to penicillin, ampicillin, vancomycin, and metronidazole.
Salvador et al, 2013 [13]	47/male	Breakthrough bacteremia with neutropenic fevers presenting with abdominal pain	ALL on chemotherapy	Susceptible to metronidazole and moxifloxacin but resistant to ceftriaxone.
Vanderhofstadt et al, 2010 [14]	51/male	The patient was completely asymptomatic. Routine blood cultures prior to the start of induction chemotherapy revealed C. tertium bacteremia.	Relapsing AML status post bone marrow transplant who was due to start a new course of induction chemotherapy	Susceptible to penicillin, amoxicillin-clavulanic, and metronidazole. Resistant to clindamycin.
	23/male	Neutropenic fevers without a focus of infection	Non-Hodgkin lymphoma on chemotherapy	Sensitive to amikacin, and ceftazidime but resistant to amoxicillin-clavulanic.
Saad et al, 2022 (present case)	66/female	Septic shock secondary to C. tertium bacteremia in a critically ill non-neutropenic patient with COVID-19	Perforated colonic diverticular disease with bacterial translocation	Susceptible to meropenem, metronidazole, and amoxicillin-clavulanic, and piperacillin-tazobactam.

Table 2. Summary of the Reported Cases of C. tertium Bacteremia as per Literature Review 1990 - 2022 (Including the Presented Case)

Authors/publication year

Age (years)/gender

Clinical presentation

Possible risk factors

Subspeciality testing results (if available)/antibiotics instituted to treat C. tertium

CT: computed tomography; C. tertium: Clostridium tertium; COVID-19: coronavirus disease 2019; IBD: inflammatory bowel disease; CD: Crohn’s disease; UC: ulcerative colitis.

Shah et al, 2016 [1]

82/female

Neutropenic fevers/abdominal pain and diarrhea. CT chest with ground glass opacities

Acute myeloid leukemia (AML) on chemotherapy

No susceptibility testing available. Infection was treated with vancomycin, piperacillin-tazobactam, and ciprofloxacin.

36/female

Neutropenic fevers/vomiting and diarrhea

AML on chemotherapy

Susceptible to meropenem, piperacillin-tazobactam, penicillin, and metronidazole.

42/female

Neutropenic fevers/shortness of breath and cough with a nodular infiltrate on chest CT

AML on chemotherapy

Susceptibility results were only provided to metronidazole, the patient was treated empirically with piperacillin-tazobactam and then a 2-week course of clindamycin.

55/male

Neutropenic fevers/lower abdominal pain and diarrhea

Myelodysplastic syndrome (MDS) on chemotherapy

No subspeciality testing available. Initially treated with cefepime, followed by vancomycin and piperacillin-tazobactam.

60/male

Neutropenic fevers/shortness of breath and cough and a new perihilar infiltrate on chest X-rays

AML on chemotherapy

No susceptibility testing available. Initially treated with cefepime, followed by a 2-week course of vancomycin and metronidazole.

69/male

Neutropenic fevers with ground-glass opacities on chest CT imaging

MDS on chemotherapy

No susceptibility testing available. Initially treated with vancomycin and cefepime followed by piperacillin-tazobactam for 2 weeks.

60/male

Neutropenic fevers/fatigue

AML on chemotherapy

No susceptibility testing available. Initially treated with ciprofloxacin, then switched to vancomycin and cefepime with cultures results.

Miller et al, 2001 [2]

28/male

Abdominal pain, vomiting, and watery diarrhea. CT abdomen with Crohn’s features. Colonoscopy and biopsy confirmed CD. Blood cultures grew C. tertium

No susceptibility testing available. Empirically treated with ciprofloxacin and clindamycin.

Miller et al, 2001 [2]

A case series of 32 patients including the above one [2]; 22 patients were males; age ranged widely from 16 to 75 years; 29 patients were neutropenic secondary to chemotherapy. Three non-neutropenic patients were as follows: one had spontaneous bacterial peritonitis (SBP) associated with alcoholic liver cirrhosis, one with CD, and the last one with systemic lupus erythematosus (SLE) treated with high-dose steroids.

Steyaert et al, 1999 [3]

65/male

Neutropenic fevers/abdominal pain and diarrhea

AML on chemotherapy

Resistant to ceftazidime, cefepime, and clindamycin; intermediately resistant to penicillin; and susceptible to metronidazole, and vancomycin. Initially treated with ceftazidime and amikacin that were switched to vancomycin following sensitivity results.

55/male

Neutropenic fevers/abdominal pain and diarrhea

AML on chemotherapy

Resistant to ceftazidime, cefepime, and clindamycin; intermediately resistant to penicillin; and susceptible to metronidazole, quinolones, and vancomycin. He was treated with vancomycin.

Wazir et al, 2019 [4]

62/male

Fatigue and high-grade fevers in a patient with end-stage liver disease. Ascitic fluid analysis revealed SBP. Blood cultures grew C. tertium

Alcoholic liver cirrhosis

Susceptible to meropenem, metronidazole, and penicillin. Initial empiric treatment with meropenem and vancomycin then targeted meropenem therapy for 9 days with clearance of C. tertium bacteremia.

Sutton et al, 2017 [5]

60/male

Worsening abdominal pain and fevers in the setting of chronic liver disease. Ascitic fluids culture isolated C. tertium

Alcoholic liver cirrhosis

Susceptible to meropenem, ciprofloxacin, clindamycin, and vancomycin. Initial empiric treatment with vancomycin and meropenem, then the latter was switched to ciprofloxacin and metronidazole. Repeat cultures were negative.

Chalhoub et al, 2016 [6]

54/female

Pancolitis progressed to septic shock with acute respiratory distress syndrome (ARDS). Serial blood cultures grew C. tertium

Colitis without evidence of IBD. Probable intestinal mucosal injury triggering C. tertium translocation

Susceptible to penicillin and vancomycin, resistant to clindamycin. Initially treated imipenem, vancomycin, and ciprofloxacin, the latter switched to ampicillin. The three-antibiotics regime was continued for 3 weeks with clearance of infection.

Gosbell et al, 1996 [7]

19/female

Recurrent neutropenic fevers

Acute lymphoblastic leukemia (ALL) on chemotherapy

Susceptible to penicillin, metronidazole, and vancomycin.

57/female

Vomiting and diarrhea in a patient with a known history of UC

No susceptibility testing available. C. tertium was isolated in the setting of polymicrobial isolates.

Coleman et al, 1993 [8]

15/female

Neutropenic fevers/abdominal pain and diarrhea. CT abdomen showing enterocolitis of the cecum and right colon

ALL on chemotherapy

No susceptibility testing available. Initially treated with ceftazidime, metronidazole, and gentamicin regime switched to ciprofloxacin and vancomycin when cultures grew C. tertium. Operative intervention with right hemicolectomy was indicated to control sepsis.

Tappe et al, 2004 [9]

51/female

Postoperative fever progressed to septic shock in the setting of ileus post-laparotomy and adhesiolysis

Paralytic ileus with probable mucosal injury secondary to ileus inducing C. tertium translocation

Susceptible to meropenem, imipenem, vancomycin, linezolid, and piperacillin-tazobactam, and resistant to penicillin, cefotaxime, clindamycin, and co-trimoxazole.

Milano et al, 2019 [10]

43/male

High-grade fevers due to a giant hepatic abscess 4 weeks post-appendectomy for a perforated appendix requiring radiology-guided drainage of the abscess

Perforated appendix with polymicrobial peritonitis and bacterial translocation and the recent use of broad-spectrum antibiotics

No susceptibility testing available. C. tertium was isolated in gram-negative polymicrobial blood cultures and the drained hepatic abscess substance. He was treated with radiologically guided hepatic abscess drainage conjugated with piperacillin-tazobactam.

You et al, 2015 [11]

44/female

Acute bronchopneumonia and C. tertium bacteremia identification of using 16S rRNA sequencing

Suicidal ingestion of glyphosate

Susceptible to penicillin, piperacillin/tazobactam, amoxicillin/clavulanic acid, cephalothin, cefoxitin, imipenem, and vancomycin, but resistance to cefotaxime, ceftazidime, cefepime, gentamicin, clindamycin, and metronidazole.

Ray et al, 2003 [12]

58/male

Necrotizing fasciitis of distal lower extremity requiring fasciotomy

History of non-Hodgkin lymphoma status post-chemotherapy 6 months prior to presentation. Alcoholic liver disease

No susceptibility testing available. The patient was treated with imipenem, vancomycin, and metronidazole.

40/male

Necrotizing fasciitis of proximal lower extremity requiring extensive fasciotomy

Motor vehicle accident with multiple lower extremities and abdominal injuries

Susceptible to penicillin, ampicillin, vancomycin, and metronidazole.

Salvador et al, 2013 [13]

47/male

Breakthrough bacteremia with neutropenic fevers presenting with abdominal pain

ALL on chemotherapy

Susceptible to metronidazole and moxifloxacin but resistant to ceftriaxone.

Vanderhofstadt et al, 2010 [14]

51/male

The patient was completely asymptomatic. Routine blood cultures prior to the start of induction chemotherapy revealed C. tertium bacteremia.

Relapsing AML status post bone marrow transplant who was due to start a new course of induction chemotherapy

Susceptible to penicillin, amoxicillin-clavulanic, and metronidazole. Resistant to clindamycin.

23/male

Neutropenic fevers without a focus of infection

Non-Hodgkin lymphoma on chemotherapy

Sensitive to amikacin, and ceftazidime but resistant to amoxicillin-clavulanic.

Saad et al, 2022 (present case)

66/female

Septic shock secondary to C. tertium bacteremia in a critically ill non-neutropenic patient with COVID-19

Perforated colonic diverticular disease with bacterial translocation

Susceptible to meropenem, metronidazole, and amoxicillin-clavulanic, and piperacillin-tazobactam.