CASE REPORT |
https://doi.org/10.5005/jp-journals-11006-0061 |
Therapeutic Conundrum: Infective Endocarditis due to Extensively Drug-resistant Pseudomonas aeruginosa Treated with Ceftazidime/Avibactam Monotherapy: A Case Report
1Department of Infectious Diseases, Deenanath Mangeshkar Hospital & Research Center, Pune, Maharashtra, India
2Department of Transplant Infectious Diseases, Deenanath Mangeshkar Hospital & Research Center, Pune, Maharashtra, India
3,4Department of Microbiology, Deenanath Mangeshkar Hospital & Research Center, Pune, Maharashtra, India
5Department of Cardiology, Deenanath Mangeshkar Hospital & Research Center, Pune, Maharashtra, India
6Department of Cardio-thoracic and Vascular Surgery, Deenanath Mangeshkar Hospital & Research Center, Pune, Maharashtra, India
7Department of Medicine, Deenanath Mangeshkar Hospital & Research Center, Pune, Maharashtra, India
8Department of Cardiac Anesthesia, Deenanath Mangeshkar Hospital & Research Center, Pune, Maharashtra, India
9Department of Medicine, Bharati Vidyapeeth Medical College, Pune, Maharashtra, India
10Department of Research, Deenanath Mangeshkar Hospital & Research Center, Pune, Maharashtra, India
Corresponding Author: Parikshit S Prayag, Department of Transplant Infectious Diseases, Deenanath Mangeshkar Hospital & Research center, Pune, Maharashtra, India, Phone: +91 7420079058, e-mail: pprayag100@gmail.com
Received on: 31 May 2023; Accepted on: 22 June 2023; Published on: 18 August 2023
ABSTRACT
Infective endocarditis (IE) is a significant cause of mortality and morbidity, especially in patients with underlying acquired structural heart disease in developing countries. IE caused by non-Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella (HACEK) gram-negative bacteria (GNB) accounts for approximately 2% of all cases and is characterized by high mortality. Pseudomonas aeruginosa (P. aeruginosa) IE accounts for <0.4% of all endocarditis cases. Gram-negative endocarditis is further compounded by the problem of antimicrobial resistance. We report a very rare case of carbapenem-resistant P. aeruginosa IE (CRIE) from India to highlight the difficulties of managing such cases with the challenges of antimicrobial resistance in our settings.
How to cite this article: Ajapuje P, Prayag PS, Patwardhan S, et al. Therapeutic Conundrum: Infective Endocarditis due to Extensively Drug-resistant Pseudomonas aeruginosa Treated with Ceftazidime/Avibactam Monotherapy: A Case Report. Indian J Crit Care Case Rep 2023;2(4):88–90.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
Keywords: Carbapenem-resistant, Case report, Pseudomonas aeruginosa infective endocarditis, Ceftazidime/Avibactam, Gram-negative infective endocarditis, Infective endocarditis, Pseudomonas aeruginosa infective endocarditis.
INTRODUCTION
Infective endocarditis (IE) is a significant cause of mortality and morbidity, especially in patients with underlying acquired structural heart disease in developing countries. Gram-negative bacteria (GNB) account for 1.3–10% of all episodes of endocarditis.1,2 Gram-negative IE is predominantly due to Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella kingae, which are collectively termed the Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella (HACEK) group. Other rare causes include enterobacteriaceae and nonfermenting GNB (NF-GNB).
According to the International Collaboration on Endocarditis-prospective cohort study results, IE caused by non-HACEK GNB contributes toward 2% of all cases of IE approximately and is characterized by high mortality.3
Escherichia coli was reported to be the most common pathogen, followed by Pseudomonas aeruginosa (P. aeruginosa).3,4,5P. aeruginosa IE accounts for <0.4% of all endocarditis cases.4 It is more commonly associated with intravenous drug abuse and cardiac implantable electronic devices and is primarily associated with right-sided endocarditis.4,6 A literature review of 26 cases of left-sided P. aeruginosa IE demonstrated that the majority of the cases were related to previous invasive medical interventions and had a high mortality rate (64%) as compared to right-sided IE.7,8
Gram-negative endocarditis is further compounded by the problem of antimicrobial resistance.9 There is sparse data globally on the optimal management of carbapenem-resistant P. aeruginosa IE (CRIE). We describe an unusual case of CRIE from India to highlight the difficulties of managing such cases with the challenges of antimicrobial resistance in our settings.
CASE DESCRIPTION
A 57-year-old male with hypertension (HTN) and diabetes mellitus underwent a percutaneous coronary intervention to the obtuse marginal coronary arteries in November 2022. He had an episode of urinary tract infection 3 months later, which was treated with oral cephalosporins. A month later, he presented with 3 days of fever and breathlessness. On admission, the patient was hypoxic, febrile, and tachypneic. His arterial blood pressure was reported to be 80/50 mm Hg. A systolic mitral murmur was audible. He was started on noradrenaline and oxygen support in the intensive care unit. The blood testing revealed a hemoglobin level of 9.4 gm%, a total leukocyte count of 12530/mm, and procalcitonin of 4.82 ng/mL. Three sets of blood cultures were sent. Transthoracic and transesophageal echography showed mobile vegetation that was shown to be attached to the anterior mitral leaflet with severe eccentric mitral regurgitation (Fig. 1).
Fig. 1: Transesophageal echocardiography showing the mitral valve with vegetation (12 × 4 mm), attached to the ventricular surface of the anterior leaflet (arrow)
Empirical therapy with intravenous meropenem and vancomycin was initiated. About 48 hours later, a nonfermentative gram-negative bacillus was isolated in the blood. The isolate was identified to be P. aeruginosa by MALDI-TOF MS (matrix-assisted laser desorption and ionization-time of flight mass spectrometry), Bruker Daltonics Bremen, Germany. A multiplex polymerase chain reaction and dot-blot hybridization panel done by Sepsis Flow chip. assay (Master Diagnostica, Granada, Spain) showed the presence of the Guyana extended-spectrum (GES) β-lactamase enzyme. Meropenem and vancomycin were discontinued, and ceftazidime/avibactam was initiated. Inotropes were stopped 48 hours later. Antimicrobial susceptibility was performed using BD Phoenix M50 and the results were interpreted according to the Clinical and Laboratory Standards Institute breakpoints (Table 1).
| Antibiotic | Interpretation | Minimum inhibitory concentration µg/mL |
|---|---|---|
| Ceftazidime/avibactam | S | 8/4 |
| Colistin | I | <1 |
| Piperacillin/tazobactam | R | 64/4 |
| Amikacin | R | >32 |
| Gentamicin | R | >8 |
| Ciprofloxacin | R | >2 |
| Levofloxacin | R | >4 |
| Ceftazidime | R | >16 |
| Aztreonam | R | >8 |
| Meropenem | R | 8 |
| Imipenem | R | >8 |
I, intermediate; R, resistant; S, sensitive
Repeat blood cultures drawn on the 7th day of admission were reported to be negative. On the 10th day of admission, mitral valve replacement with a bioprosthetic valve was performed on the patient. The valve tissue grew P. aeruginosa with the same susceptibility pattern as shown in Table 1. A 6-week course of ceftazidime/avibactam was completed by the patient, after which the patient remained afebrile.
DISCUSSION
Pseudomonas aeruginosa (P. aeruginosa) is a rare cause of non-HACEK gram negative endocarditis. It is most frequently associated with intravenous drug abuse, which usually causes right-sided endocarditis. Other risk factors include endovascular devices as well as implanted prosthetic cardiac valves. Left-sided endocarditis which is caused by P. aeruginosa is extremely rare.8
Healthcare-associated IE (HAIE) has been previously described as endocarditis developing after 48 hours or within 6 months of hospitalization, and coronary intervention has been recognized as an important risk factor.10 This case highlights the need to ensure stringent infection control practices in the setting of coronary interventions. Pseudomonas can spread through contaminated hands, equipment, or surfaces. Awareness and education regarding HAIE must be increased in our settings.
Pseudomonas IE presents a unique diagnostic and therapeutic challenge in India. It is essential to draw blood cultures before administering therapy. Gram-negative resistance is a problem of considerable magnitude in India, and hence, the laboratory must have the expertise to determine the antimicrobial susceptibility in these cases. Access to both genotypic as well as phenotypic susceptibility testing is ideal, and this expertise may be available at very few centers across the country. Our patient showed the presence of the GES enzyme, which can be a carbapenemase. Gram-negative endocarditis, especially when caused by multidrug-resistant pathogens, can be associated with significant mortality.5 The 2015 European Society of Cardiology guidelines for the management of IE recommend treatment with two antipseudomonal antibiotics therapy for approximately 6 weeks for endocarditis caused by Pseudomonas species.11 However, when dealing with pandrug-resistant P. aeruginosa endocarditis, the options are limited. Also, for treating those carbapenem-resistant isolates which are susceptible to β-lactam-β-lactamase inhibitors (BL-BLI) such as ceftazidime/avibactam or ceftolozane tazobactam, it is uncertain whether an additional agent, especially when resistant in vitro, will add any benefit. In our case, the organism was a GES producer, an enzyme that is expected to be inhibited by avibactam. All other antimicrobials were resistant (except colistin), thus, severely compromising our therapeutic options. We treated this patient with ceftazidime/avibactam monotherapy with a favorable clinical outcome. Lima et al. reported a case of P. aeruginosa IE successfully treated with ceftazidime/avibactam monotherapy.12 Our case reinforces this approach, wherein ceftazidime avibactam monotherapy can be used for susceptible isolates. There is limited data from India regarding the best approach to these situations. In a study of 53 patients from India published in 2018, one patient who had P. aeruginosa IE was treated with colistin, ciprofloxacin, and ceftazidime.13
Combining medical and surgical therapy may be an important part of the management of such patients. In an analysis of 27 patients with Pseudomonas IE, 15 underwent surgery in addition to medical management.7 Our patient did undergo a valve replacement surgery. Evaluating patients with gram-negative endocarditis from the viewpoint of surgical therapy forms an important part of management.
CONCLUSION
This is a very rare case of carbapenem-resistant P. aeruginosa IE reported from India. It depicts the therapeutic challenges in our settings, wherein we may not have two susceptible agents available. Our case shows that newer BL-BLI combinations, such as ceftazidime avibactam, when susceptible, can be used as monotherapy. It is only the second such case reported in literature wherein ceftazidime/avibactam monotherapy has been used. Valvular surgery should be considered in these patients.
ORCID
Preeti Ajapuje https://orcid.org/0000-0003-4095-3028
Parikshit S Prayag https://orcid.org/0000-0003-2102-7627
Sampada Patwardhan https://orcid.org/0000-0003-0998-5742
Amrita Prayag https://orcid.org/0000-0002-2498-9576
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