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 Table of Contents  
Year : 2022  |  Volume : 19  |  Issue : 1  |  Page : 36-38

Newer drug for the resistant bug: A case report of spondylodiscitis with Klebsiella pneumoniae producing carbapenemase managed successfully with ceftazidime-avibactam

1 Department of Microbiology, Central Laboratory, People Tree Hospitals, Bengaluru, Karnataka, India
2 Department of Infectious Diseases, Manipal Hospitals, Bengaluru, Karnataka, India
3 Department of Spine Surgery and Orthopedics, People Tree Hospitals, Bengaluru, Karnataka, India

Date of Submission02-Feb-2022
Date of Acceptance26-Feb-2022
Date of Web Publication26-Jun-2022

Correspondence Address:
Sushma Krishna
Department of Microbiology, Central Laboratory, People Tree Hospitals, Yeshwanthpur, Bengaluru - 560 022, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joasis.joasis_2_22

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Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae are multidrug resistant organisms that have been increasingly recognized to cause infections with high mortality. The therapeutic options available for treating such infections stand severely compromised. The use of ceftazidime-avibactam in bacteremia and other infections by these organisms has been reported. We report a case of spondylodiscitis caused by KPC-KP diagnosed by pan-bacterial DNA screen and successfully treated with this relatively newer antibiotic. This report highlights the importance of the utility of molecular diagnostic tests in routine practice.

Keywords: Ceftazidime-avibactam, Klebsiella pneumoniae, multidrug resistant, spondylodiscitis

How to cite this article:
Krishna S, Mishra N, Chath NN, Swamy G, Pala SK. Newer drug for the resistant bug: A case report of spondylodiscitis with Klebsiella pneumoniae producing carbapenemase managed successfully with ceftazidime-avibactam. J Orthop Assoc South Indian States 2022;19:36-8

How to cite this URL:
Krishna S, Mishra N, Chath NN, Swamy G, Pala SK. Newer drug for the resistant bug: A case report of spondylodiscitis with Klebsiella pneumoniae producing carbapenemase managed successfully with ceftazidime-avibactam. J Orthop Assoc South Indian States [serial online] 2022 [cited 2023 Apr 1];19:36-8. Available from: https://www.joasis.org/text.asp?2022/19/1/36/348310

  Introduction Top

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) are multidrug-resistant organisms (MDROs) that have been recognized to cause infections with high mortality due to the difficulty in treating them. These are enzymes that are capable of hydrolyzing “carbapenem” class of drugs, which are the current reserved or high-end antibiotics to treat most of the severe Gram-negative infections. The therapeutic options available for treating such infections thus stand severely compromised as the antibiotic pipeline for Gram-negative Bacilli has run dry from decades. There have been a handful of cases of KPC osteomyelitis and bone-related infections reported with varied patient responses to different antibiotic therapies.[1],[2],[3] Ceftazidime-avibactam (C-A) is a newer broad-spectrum antibiotic, active against many MDROs, including carbapenem-resistant strains. Its clinical use in treating spondylodiscitis has not been reported and we describe our first patient who was successfully treated with the same. The experience adds on to the therapeutic options of treating MDRO infections today.

  Case Report Top

A 62-year-old retired administrative employee presented with complaints of lower backache for 2 months. Pain was worse on turning either side and on sitting. There was no history of trauma or other comorbidities. There was no history of recent travel, animal contact, or exposure to active pulmonary Koch. He had a history of mild COVID-19 disease three months ago and had recovered completely. On examination of the spine, T10-T11 were tender, movements restricted, no neurological deficits. His erythrocyte sedimentation rate (ESR) at presentation was 50 mm/h and C-reactive protein was 1.85 mg/dL. His white blood cell counts were 10,970 c/cmm with 97% neutrophils and 1.6% lymphocytes. HIV, HBSAg, and HCV serology testing were negative. He was put on nonsteroidal anti-inflammatory drugs for 10 days and was asked for follow-up. He returned after a month with persisting pain and underwent a magnetic resonance imaging (MRI) and computed tomography (CT), both of which showed erosion of T10-T11 vertebral bodies [Figure 1]. A provisional diagnosis of T10-T11 spondylodiscitis was made. CT-guided biopsy was taken at the same sitting to rule out infective pathology. GeneXpert was negative and there was no growth in aerobic and fungal cultures. Brucella titers were insignificant. He underwent T8-L1 posterior instrumentation with stabilization (JP screw system, Sandvik Coromant, Japan), T10-11 Laminectomy with T11 transpedicular biopsy. The biopsy tissue was sent for laboratory investigations. He had postoperative urinary retention, required catheterized for 5 days, and was treated with ceftriaxone and analgesics for 7 days. The pain subsided temporarily, the wound was healthy, and the patient was discharged while awaiting the other laboratory reports. The histopathology findings of the spine tissue were that of mild nonspecific inflammatory process, acute on chronic inflammatory pathology without granuloma or necrosis. No acid-fast bacilli were seen on ZN stain. GeneXpert was negative for the second time. Mantoux was negative. Aerobic bacterial cultures, blood and fungal culture on extended incubation remained sterile throughout. However, the tissue sent for real-time polymerase chain reaction (PCR) pan-bacterial DNA screen was detected KPC. Microbiologist and infectious disease experts were consulted and the patient was started on newer antibiotic C-A 2.5 g IV TDS for a period of 8 weeks (included 1 week hospitalization under scrutiny and later continued at home). He was on oral tigecycline 600 mg BD for the subsequent month. He tolerated the drug well. Postantibiotic course, his ESR declined to 20 mm/hr with all other parameters within normal range. He has remained pain free till date and is due for repeat MRI.
Figure 1: Erosion of T10-T11 vertebral bodies suggestive of spondylodiscitis seen in magnetic resonance imaging

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  Discussion Top

E. coli, Klebsiella Spp., Enterobacter Spp., and other Enterobacteriaceae are the common Gram-negative bacilli (GNB) implicated in the etiology of spondylodiscitis. The emergence of carbapenem resistance in Enterobacteriaceae strains is the result of a number of mechanisms, alone or in combination such as production of a) serino β-lactamases (KPC, or KPC, and OXA-48), b) metallo β-lactamases (Verona Integron-Mediated Metallo-β-lactamase, and New Delhi metallo-beta-lactamase) and c) Extended-Spectrum Beta-Lactamases with/without AmpC β-lactamases which may be in association with alterations in the expression of outer membrane porins as well. Whatsoever, the terminologies stand for at bench; these infections pose a challenge to clinicians as the antibiotics to treat Gram-negative MDROs infections are not many. C-A has recently been advocated as superior in terms of clinical success, reduction of mortality rates, and tolerability, both in monotherapy or combined with other antimicrobial agents for bacteremia, UTI, and other infections.[4],[5] The therapeutic options for osteomyelitis and soft tissue infections caused by KPC-KP include colistin with/without high dose carbapenems, tigecycline alone/or in combination, and aminoglycosides in combination. Notably, compared to colistin-based regimens, there have been two reported cases of successfully treated bacterial osteomyelitis (6 weeks therapy) and a prosthetic joint infection (2 weeks therapy).[6],[7],[8]

While the newer Beta lactum-Beta lactum inhibitors such as cefipime-zidebactam, ceftaroline-avibactam, aztreonam -avibactam are under trails and do not yet have the clinical in vivo efficacy data against KPC-KP, Imipenem-relebactam[9] meropenem-varbobactam[10] have shown promise in non-orthopaedic trials. The risk factors quoted for the MDRO strain isolation include previous hospitalizations, presence of indwelling devices, recent surgical procedure, and prior colonization.[11] As these factors were generic, it was challenging to identify the origin of KPC-KP infection in this patient. We hypothesized that the possible source of the organism could be the urinary catheter. We also considered a possibility of the organism being a contaminant on pan-bacterial DNA screen. We however decided to start definitive antibiotic therapy based on the benefit of doubt to which the patient responded well. To our knowledge, there has been no other local report of KPC-KP isolated in the spine where C-A has been administered. On the other end, in this era of antibiotic resistance, there is also misuse of newer available antibiotics and careful selection of recipients becomes important. Although the dosage and duration for treating spondylodiscitis stands indetermined, we recommend judicious usage of this reserved drug for KPC-KP infections as the bacterial resistance has already emerged.[12]

Rapid identification with molecular mechanism detection of resistance is an important tool in guiding antibiotic therapy. This report also highlights the importance of the availability and utility of molecular tests at laboratories when the conventional cultures remain less contributory in diagnosis. The molecular revolution that the country is witnessing remains confined to COVID-19 for now and the real-time PCR assay panel cost for other organisms offered by a few big private players continues to be exuberant, beyond the reach of common man. It is hoped that the future days of the country brings better access to non-COVID molecular tests to improve patient care.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Odio CD, Duin DV, Cober E, Teixeira-Johnson L, Schmitt S, Sanctis SD. Carbapenem-resistant Klebsiella pneumoniae osteomyelitis and soft tissue infections: A descriptive case series. J Infect Dis Ther 2015;3:1-4.  Back to cited text no. 1
Schelenz S, Bramham K, Goldsmith D. Septic arthritis due to extended spectrum beta lactamase producing Klebsiella pneumoniae. Joint Bone Spine 2007;74:275-8.  Back to cited text no. 2
Chen PL, Yan JJ, Wu CJ, Lee HC, Chang CM, Lee NY, et al. Salvage therapy with tigecycline for recurrent infection caused by ertapenem-resistant extended-spectrum β-lactamase-producing Klebsiella pneumoniae. Diagn Microbiol Infect Dis 2010;68:312-4.  Back to cited text no. 3
Shields RK, Nguyen MH, Chen L, Press EG, Potoski BA, Marini RV, et al. Ceftazidime-avibactam is superior to other treatment regimens against carbapenem-resistant Klebsiella pneumoniae bacteremia. Antimicrob Agents Chemother 2017;61:e00883-17.  Back to cited text no. 4
Tumbarello M, Trecarichi EM, Corona A, De Rosa FG, Bassetti M, Mussini C, et al. Efficacy of ceftazidime-avibactam salvage therapy in patients with infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Clin Infect Dis 2019;68:355-64.  Back to cited text no. 5
Cani E, Moussavi F, Ocheretyaner E, Sharma R, Brown C, Eilertson B. Carbapenem-resistant Klebsiella pneumoniae vertebral osteomyelitis in a renal transplant recipient treated with ceftazidime-avibactam. Transpl Infect Dis 2018;20:e12837.  Back to cited text no. 6
De León-Borrás R, Álvarez-Cardona J, Vidal JA, Guiot HM. Ceftazidime/avibactam for refractory bacteremia, vertebral diskitis/osteomyelitis with pre-vertebral abscess and bilateral psoas pyomyositis secondary to Klebsiella pneumoniae carbapenemase-producing bacteria (KPC). P R Health Sci J 2018;37:128-31.  Back to cited text no. 7
Schimmenti A, Brunetti E, Seminari E, Mariani B, Cambieri P, Orsolini P. Prosthetic joint infection from carbapenemase-resistant Klebsiella pneumoniae successfully treated with ceftazidime-avibactam. Case Rep Infect Dis 2018;2018:1854805.  Back to cited text no. 8
Motsch J, de Oliveira C, Stus V, Koksal I, Lyulko O, Boucher HW, et al. RESTORE-IMI1: Multi-Center RCT Comparing Efficacy and Safety of Imipenem-Relebactam Versus Colistin Plus Imipenem in Patients with Imipenem-Non-Susceptible Bacterial Infections. 2018, 28th European Congress of Clinical Microbiology & Infectious Diseases, 21-24; 2018.  Back to cited text no. 9
Wunderink RG, Giamarellos-Bourboulis EJ, Rahav G, Mathers AJ, Bassetti M, Vazquez J, et al. Effect and safety of meropenem-vaborbactam versus best-available therapy in patients with carbapenem-resistant Enterobacteriaceae infections: The TANGO II Randomized Clinical Trial. Infect Dis Ther 2018;7:439-55.  Back to cited text no. 10
Bassetti M, Carnelutti A, Peghin M. Patient specific risk stratification for antimicrobial resistance and possible treatment strategies in gram-negative bacterial infections. Expert Rev Anti Infect Ther 2017;15:55-65.  Back to cited text no. 11
Zhou J, Yang J, Hu F, Gao K, Sun J, Yang J. Clinical and molecular epidemiologic characteristics of ceftazidime/avibactam-resistant carbapenem-resistant Klebsiella pneumoniae in a neonatal Intensive Care Unit in China. Infect Drug Resist 2020;13:2571-8.  Back to cited text no. 12


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