Successful Treatment of Carbapenemase-Producing Pandrug-Resistant Klebsiella pneumoniae Bacteremia

Abstract

New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated. CASE PRESENTATIONA 64-year-old female with a history of diabetes mellitus developed Clostridium difficile colitis with toxic megacolon requiring total colectomy. As a complication of the total colectomy, she had a volvulus requiring extensive resection of necrotic small bowel with resultant total parenteral nutrition-dependent short bowel syndrome (only 15 cm of small bowel left). The patient was referred to our institution for an intestinal transplant. Induction immunosuppression consisted of antithymocyte globulin at 2 mg/kg of body weight intravenously (i.v.) (5 doses), methylprednisolone at 500 mg i.v. every 24 h (q24h) (4 doses, followed by a slow taper over the first 2 weeks), and rituximab at 150 mg/m 2 i.v. (1 dose). Maintenance immunosuppression consisted of basiliximab at 40 mg i.v. every 4 weeks for the first 3 months, tacrolimus, and low-dose prednisone. The antimicrobial prophylaxis regimen consisted of ganciclovir (5 mg/kg i.v. q12h for 2 weeks, followed by valganciclovir at 900 mg per os [p.o.] daily) and trimethoprimsulfamethoxazole (80/400 mg p.o. three times a week) for cytomegalovirus and Pneumocystis jirovecii pneumonia prophylaxis, respectively. No multidrug-resistant organisms were identified by rectal and nasal surveillance cultures at the time of the transplant.The early posttransplant course was complicated by an intraabdominal hematoma on postoperative day 1, which required emergent surgical exploration and evacuation. Abdominal wound closure was performed on postoperative day 8. On postoperative day 12, the patient required another surgical exploration with intraoperative findings of pancreatitis with a small peripancreatic collection. Cultures from this collection obtained in the operating room yielded a heavy growth of Klebsiella pneumoniae. A Hodge test was positive, indicating carbapenemase production. The presence of the Klebsiella pneumoniae carbapenemase (KPC) gene was confirmed using the Verigene (Nanosphere, Inc., Northbrook, IL) Gram-negative blood culture nucleic acid test. The class B (IMP-type metallo-␤-lactamase, New Delhi metallo-␤-lactamase [NDM], and Verona integron-encoded metallo-␤-lactamase [VIM]) and class D (oxacillinase [OXA]-type) carbapenemase genes were not detected. The isolate was resistant to aminoglycosides but susceptible to tigecycline (MIC, 0.38 g/ml) and colistin (MIC, 0.19 g/ml). The patient was started on a combination of tigecycline (1 dose of 100 mg i.v., followed by 50 mg i.v. q12h) and colistin (2.5 mg i.v. q12h) and completed a 14-day course for complicated intra-abdominal infection (cIAI) due to carbapenem-resistant Klebsiella...

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms

“…The first was a case report of a 64-year-old woman who received compassionate-use CAZ-AVI for bacteremia caused by KPC-producing K. pneumoniae that did not respond to colistin and dual-carbapenem therapy. She was treated successfully with CAZ-AVI and ertapenem (22). The second was a case series of three patients (aged 72 to 89 years) with CRE bacteremia that had not responded to previous antibiotics.…”

Global Dissemination of bla KPC into Bacterial Species beyond Klebsiella pneumoniae and In Vitro Susceptibility to Ceftazidime-Avibactam and Aztreonam-Avibactam

“…KPC-producing MDR isolates often remain susceptible only to tigecycline, polymyxins, and some aminoglycosides (e.g., gentamicin or amikacin); however, monotherapy with tigecycline or colistin is frequently associated with high treatment failure rates (4,(8)(9)(10)42). Ceftazidime-avibactam was recently used in combination with ertapenem to successfully treat a patient infected with a KPC-producing K. pneumoniae isolate that had become resistant to tigecycline and colistin after treatment for successive nosocomial infections (43). However, one KPC-producing isolate that was resistant to ceftazidime-avibactam via an unknown mechanism has also been reported (44).…”

耐碳青霉烯类肺炎克雷白杆菌临床分布及整合素1与其耐药关系的研究

“…Kp is also a potential nosocomial multidrug resistant bacterium. 2 Carbapenem-resistant Klebsiella pneumoniae (CRKP) is resistant to many structurally unrelated antibiotics because of its dominant array of chromosome and plasmid-mediated antibiotic resistance factors. 3 It also could capture many resistance genes from other bacteria.…”