A total of 251 hospitalized patients who received tigecycline between January 2007 and July 2013 at our institution were screened for inclusion in this study. Of these patients, nine were treated with tigecycline for CDI. Two patients were excluded due to <48 h of treatment with tigecycline. In both of these cases, alternative agents for CDI were used according to the decision of a treating physician. A total of seven patients met study criteria and were included in the final analysis.
Case Reports
Case 1 occurred in a 64-year-old female who was admitted for community onset CDI. This patient had multiple risk factors for CDI, including recent antibiotic use (meropenem and vancomycin for pneumonia, and levofloxacin for chronic leukopenia) and immunosuppression. She was initially leukopenic secondary to end-stage liver disease awaiting transplantation with mild CDI (WBC 600/μL, serum creatinine 138% relative to baseline). She was treated with intravenous metronidazole 500 mg three times daily for CDI starting on hospital day 1. On hospital day 2, follow-up PCR for toxigenic C. difficile remained positive. Her early hospital course was unremarkable; however, she developed ileus, nausea, and vomiting on hospital day 4 and her CDI had progressed from mild to a severe complicated case. The patient was transferred to the intensive care unit (ICU) and oral vancomycin 125 mg four times daily was added to the regimen. On hospital day 6, the patient’s ileus remained unresolved, her serum creatinine level increased to 188% of the premorbid level and she developed severe abdominal pain. Due to the concerns for limited effectiveness of oral vancomycin in the setting of ileus, intravenous tigecycline was added to the regimen on hospital day 6 as a 100-mg loading dose followed by 50-mg doses twice daily. This patient was treated with a combination of intravenous tigecycline, oral vancomycin, and intravenous metronidazole for 10 days. No side effects of tigecycline therapy were noted in the electronic medical record. Follow-up PCR for toxigenic C. difficile was negative at the end of treatment. This patient was at high risk of recurrence due to her chronic antibiotic use and pancytopenia. Therefore, she was discharged to a long-term care facility where she completed a 30-day vancomycin taper. She had no subsequent recurrence of CDI on record.
Case 2 occurred in a 46-year-old male who was admitted to the ICU with severe diarrhea and septic shock requiring 13 L fluid resuscitation and vasopressors. The patient presented with severe leukocytosis (WBC 35,400/μL) and renal impairment (serum creatinine increased 166% of the premorbid level). This patient had a number of risk factors for CDI, including admission from a long-term care facility and multiple prior antibiotic use (see Table
1 for full listing). He was treated initially with oral metronidazole 500 mg three times daily. Oral metronidazole was switched to intravenous and oral vancomycin 125 mg four times daily was added on hospital day 2 upon detection of toxigenic
C. difficile. At this point, the patient was intubated due to decreasing respiratory function and pulmonary edema. He also had other symptoms of severe complicated CDI, included nausea and vomiting, abdominal pain, colonic wall thickening, and ascites. Oral vancomycin was changed to rectal vancomycin 500 mg four times daily on hospital day 3 due to the development of paralytic ileus. This regimen continued through hospital day 7, with fever, ileus, and abdominal pain resolving. On hospital day 8, the patient again developed diarrhea with abdominal pain and persisting leukocytosis (WBC 24,300/μL). Due to these non-resolving symptoms and the severity of the patient’s condition, intravenous tigecycline was added on hospital day 8 as a 100-mg loading dose followed by 50 mg twice daily. Clinical cure was achieved after 8 days of treatment with tigecycline, rectal vancomycin, and intravenous metronidazole. Due to the high risk of recurrence, the patient completed a vancomycin taper upon discharge to a long-term care facility. There was no documented recurrence of CDI on record.
Table 1
Summary of patient characteristics, risk factors, antimicrobial treatment, and clinical outcomes by case of Clostridium difficile infection
1 | F (64) | 7 | Severe complicated | 5 | LVX, VAN, MEM | Community | TIG + VAN + MTZ | 10 | Yes | Yes | Yes | No | No |
2 | M (46) | 2 | Severe complicated | 5 | TZP, VAN, LVX, TOB, ERY, FEP, MTZ, LZD, CFZ | LTC facility | TIG + VAN + MTZ | 8 | Yes | Yes | Yes | No | No |
3 | M (38) | 4 | Severe complicated | 3 | TZP, SAM | Hospital | TIG + VAN | 8 | Yes | Yes | No | No | No |
4 | F (80) | 13 | Severe complicated | 6 | VAN, LVX, TZP | Community | TIG + VAN + MTZ | 6 | Yes | Yes | Yes | No | No |
5 | M (68) | 6 | Severe complicated | 6 | TMP-SMX, LVX, LZD, FEP | Hospital | TIG + VAN + MTZ | 21 | Yes | –a
| No | No | Yes |
6 | F (84) | 9 | Severe complicated | 8 | TMP-SMX | LTC facility | TIG + VAN + MTZ | 3 | No | –b
| No | No | Yes |
7 | F (73) | 8 | Severe | 5 | TZP, LVX, VAN | Hospital | TIG + MTZ | 4 | Yes | Yes | No | No | No |
Case 3 occurred in a 38-year-old male who was initially admitted due to acute hypoxic respiratory failure and necrotizing pancreatitis. For this infection, he was treated with piperacillin–tazobactam, which was switched to ampicillin–sulbactam after 10 days by the consulting infectious diseases specialist. On hospital day 25, the patient started developing copious diarrhea (>15 loose stools per day), fever (38.4 °C), and leukocytosis (WBC 13,500/μL) consistent with C. difficile sepsis and severe complicated CDI. The patient’s serum creatinine levels increased 143% relative to baseline. Upon confirmation of CDI on hospital day 26, intravenous metronidazole 500 mg three times daily was initiated. Tigecycline was added on hospital day 27 for dual coverage of enterococcal pancreatitis and C. difficile. Oral vancomycin 250 mg four times daily was also added at this time and metronidazole was discontinued by decision of the treating physician. Fever and leukocytosis subsided and diarrhea improved on 8 days of combination therapy with tigecycline and oral vancomycin. There was no recurrence of CDI on record.
Case 4 occurred in an 80-year-old female who was admitted due to increasing fatigue and copious diarrhea consistent with community onset CDI. Her risk factors for CDI included advanced age and recent antibiotic use (vancomycin, levofloxacin, and piperacillin–tazobactam). This patient’s initial severity of illness was mild (WBC 9,100/μL, serum creatinine 116% of the premorbid level) and she was treated with oral metronidazole 500 mg three times daily beginning on hospital day 1. After 3 days of metronidazole treatment, her abdominal pain had improved, but the diarrhea persisted and her WBC began trending upward (16,500/μL). On hospital day 4, the patient developed septic shock secondary to CDI. As her CDI had progressed to a severe complicated case, intravenous tigecycline and vancomycin 250 mg four times daily were added. Tigecycline was given as a 100-mg loading dose followed by 50 mg twice daily. The patient was treated successfully with 6 days of triple therapy with tigecycline, vancomycin, and metronidazole. Due to the high risk of CDI recurrence in this patient, a vancomycin taper was completed. The patient was discharged to home and had no CDI recurrence within 28 days of follow-up.
Case 5 occurred in a 68-year-old male who was admitted to the hospital for febrile neutropenia secondary to pre-B cell acute lymphoblastic leukemia. This patient had multiple risk factors for CDI, including advanced age, hematologic malignancy, multiple prior antibiotic use (trimethoprim–sulfamethoxazole, levofloxacin, linezolid, and cefepime), prior chemotherapy use, and hospitalization. On hospital day 6, the patient developed acute respiratory distress and severe sepsis (4/4 SIRS criteria). On hospital day 7, the patient developed diarrhea and C. difficile toxin was detected. This case was classified as severe complicated CDI and treated initially with two days of intravenous metronidazole 500 mg three times daily and oral vancomycin 125 mg four times daily. On hospital day 9, tigecycline was added due to persisting diarrhea (>800 mL liquid stool) and fever (38.2 °C). The patient’s fever resolved on hospital day 11, diarrhea resolved on hospital day 14, and clinical cure was achieved. Triple therapy with tigecycline, vancomycin, and metronidazole was continued for a total of 21 days due to concerns for recurrence in the context of the patient’s pancytopenia. At this time, the patient was switched to palliative care due to underlying cancer with a poor overall prognosis. He tolerated treatment with tigecycline well and no side effects were reported. The patient was discharged home to hospice with no further CDI treatment. Sustained response was unevaluable due to death within 28 days of tigecycline completion.
Case 6 occurred in an 84-year-old female admitted from a nursing home with altered mental status, leukocytosis (WBC 19,300/μL), and acute kidney failure (serum creatinine increased 497% relative to baseline). The patient was admitted to the ICU with severe complicated CDI with septic shock. Intravenous metronidazole 500 mg three times daily and oral vancomycin 125 mg four times daily were started on hospital day 1. The patient’s diarrhea and leukocytosis persisted (WBC 41,200/μL) and intravenous tigecycline was added on hospital day 7 as a 100-mg loading dose followed by 50 mg twice daily. She was treated with combination tigecycline, vancomycin, and metronidazole for 3 days. The patient’s diarrhea resolved and her WBC decreased yet remained elevated (WBC 33,600/μL). Tigecycline was discontinued per the family’s decision to switch her to oral antibiotics for discharge to hospice. This patient was classified as clinical failure due to non-resolving leukocytosis and sustained response was unevaluable due to the lack of clinical cure. No side effects associated with tigecycline use were noted in the electronic medical record.
Case 7 occurred in a 73-year-old female who was initially admitted due to pneumonia and acute kidney injury. The patient was treated empirically with vancomycin, levofloxacin, and piperacillin-tazobactam. On hospital day 3, the patient developed copious diarrhea, nausea, leukocytosis (WBC 20,000/μL) and serum creatinine increased 151% of the premorbid level. Clostridium difficile toxin was detected and oral metronidazole 500 mg three times daily was initiated. Tigecycline was added on hospital day 5 based on recommendations by the consulting infectious diseases specialist. Tigecycline was initiated instead of vancomycin due to the additional coverage of the patient’s concomitant vancomycin-resistant enterococcal urinary tract infection. The patient was successfully treated with 4 days of combination therapy with tigecycline and metronidazole with resolution of all CDI symptoms. No side effects attributed to tigecycline use were noted, and she had no documented CDI recurrence on record.