Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Novel Therapy for Multidrug Resistant Gram Negative Infections in Children

(E-pub Ahead of Print)

Author(s): Brittany A Rodriguez, Jennifer E Girotto, David P Nicolau*.

Journal Name: Current Pediatric Reviews

Abstract:

The rise in multidrug-resistant (MDR) infections has become a significant problem in both the developing countries and in the United States (U.S.). Specifically, MDR gram-negative infections are emerging, affecting not only adults but children as well. The specific gram-negative organisms that have been most concerning within the pediatric population include MDR P. aeruginosa, Enterobacteriaceae, and Acinetobacter spp.

The increase in antimicrobial resistance rates is associated with various mechanisms with one of the most common being the production of beta-lactamases. Both ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) are two recently approved antibiotics in the U.S. While both of these agents are inhibitors of beta-lactamase enzymes, there are differences between them that are important to understand. At this time, the data in children for these agents are extremely limited. The aim of this review is to describe the characteristics of these agents and their potential uses in pediatric patients. Case Presentation: A 16-year-old, 60 kg, previously healthy male was admitted with a one-day history of emesis, abdominal pain, and right lower quadrant tenderness. Upon presentation, imaging and inflammatory markers were unremarkable with C-reactive protein (CRP) and white blood cell (WBC) counts of 0.35 mg/dL and 15 Thous/μL, respectively. Over the next 5 days, the patient continued to progress with peak temperatures of 39.4ºC and CRP of 28 mg/dL. At that time, a computerized tomography scan revealed perforated appendicitis that required laparoscopic surgery and drainage. The patient was started on intravenous (IV) metronidazole 1,500 mg every 24 hours and ciprofloxacin 400 mg every 12 hours. The drained fluid obtained at the time of the procedure grew an extended spectrum β-lactamase (ESBL) producing Escherichia coli that was sensitive to cefepime, ertapenem, imipenem, meropenem, gentamicin, and tobramycin. Based upon the culture and sensitivity data, ertapenem 1000 mg IV every 24 hours was begun. The patient’s fever continued to elevate with a max of 41.2ºC while receiving ertapenem for 7 days. Repeat imaging revealed a new intra-abdominal abscess which, when drained, grew a Klebsiella pneumoniae carbapenemase (KPC) producing E. coli confirmed by PCR. At that time, the patient was transitioned to ceftazidime/avibactam (CZA) 2000 mg/500 mg IV every 8 hours as a 3-hour infusionμ and metronidazole 500 mg IV every 8 hours. The KPC E. coli was determined to be resistant to ceftazidime (MIC > 256 μg/mL), ceftriaxone (MIC > 128 μg/mL), meropenem (MIC 4 μg/mL), ciprofloxacin (MIC > 32 μg/mL), levofloxacin (MIC > 32 μg/mL), tetracycline (MIC > 256 μg/mL), and colistin (MIC > 32 μg/mL). The organism was sensitive to CZA, gentamicin, tobramycin, and tigecycline (MIC 0.5 μg/mL). Initially with the change of antibiotics, the patient began to improve; however, his progress again plateaued. Gentamicin 150 mg IV every 8 hours (7.5 mg/kg/day) was added but there was still no improvement. A repeat CT scan was performed revealing a residual abscess that was drained. His antimicrobial coverage expanded to include tigecycline 50 mg IV every 12 hours (discontinuing gentamicin), and the patient was a clinical cure.

Keywords: beta-lactam/beta-lactamase inhibitor, ceftazidime/avibactam, ceftolozane/tazobactam, children, Enterobacteriaceae, multidrug resistance

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(E-pub Ahead of Print)
DOI: 10.2174/1573396314666180308150908
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