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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 11  |  Issue : 2  |  Page : 102-104

Achromobacter xylosoxidans infection in a patient with acute leukemia: characteristics and options for antibiotic therapy for a rare highly virulent gram-negative bacterium


1 Department of Clinical Hematology and Stem Cell Transplantation, Dayanand Medical College, Ludhiana, Punjab, India
2 Department of Microbiology, Dayanand Medical College, Ludhiana, Punjab, India

Date of Submission08-May-2020
Date of Decision24-May-2020
Date of Acceptance01-Jun-2020
Date of Web Publication07-Jul-2020

Correspondence Address:
Dr. Suvir Singh
Department of Clinical Haematology Stem Cell Transplantation, Dayanand Medical College, Basement Cancer Building, Ludhiana - 141 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INJMS.INJMS_37_20

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  Abstract 


Gram-negative infections are a common cause of induction mortality in acute leukemia. Multidrug-resistant (MDR) Gram-negative bacilli are common culprits, contributing to over 40% of deaths in some centers in India. A 20-year-old male with B-cell acute lymphoblastic leukemia, after 5 days of initiation on steroids at another hospital, developed rapid onset dyspnea, with signs of bilateral pneumonia and Type 1 respiratory failure. High-resolution computed tomography of the thorax showed bilateral nodular opacities with ground glassing. Galactomannan was negative, and blood culture isolated MDR Achromobacter xylosoxidans. Antibiotic sensitivity by VITEK2 indicated sensitivity only to ciprofloxacin, levofloxacin, and minocycline. Antibiotics were tailored according to sensitivity, but he had a rapidly worsening downhill course with death from respiratory failure within 72 h. This is only the third case of this organism being described in a patient with malignancy from India. MDR organisms should be suspected whenever a patient with acute leukemia has a history of being in contact with another hospital. In such patients who present with signs of sepsis, it may be reasonable to consider a “de-escalation” approach, with addition of carbapenems upfront and stepping down once cultures are available.

Keywords: Antibiotic, bacteria, cancer, infection, leukemia


How to cite this article:
Singh S, Kaur D. Achromobacter xylosoxidans infection in a patient with acute leukemia: characteristics and options for antibiotic therapy for a rare highly virulent gram-negative bacterium. Indian J Med Spec 2020;11:102-4

How to cite this URL:
Singh S, Kaur D. Achromobacter xylosoxidans infection in a patient with acute leukemia: characteristics and options for antibiotic therapy for a rare highly virulent gram-negative bacterium. Indian J Med Spec [serial online] 2020 [cited 2020 Aug 13];11:102-4. Available from: http://www.ijms.in/text.asp?2020/11/2/102/289145




  Introduction Top


Infections are the primary cause of mortality during initial induction therapy for acute leukemia. Multidrug resistant (MDR) organisms, especially Gram-negative bacilli, are increasingly becoming prominent as causative organisms in this setting. Data from India show that over 40% of deaths in induction with acute myeloid leukemia are due to MDR Gram-negative bacilli,[1] andin vitro resistance to carbapenems is being noted in over 80% of isolates from referral centers.[2] Guidelines suggest an “escalation” approach where the most common organisms are initially covered, and the antibiotic cover is extended based on clinical condition or microbiologic isolates. Similar practice with the early addition of antifungals continues to be the common practice among centers treating leukemia. We report a patient who presented with a bloodstream infection (BSI) with Achromobacter xylosoxidans, with respiratory involvement and a rapidly downhill course.


  Case Report Top


Mr. K, a 20-year-old gentleman, was evaluated elsewhere with undifferentiated acute febrile illness for 7 days. On evaluation, he was noted to have hepatosplenomegaly with leukocytosis (WBC Count = 130,000/ml with 80% blasts) in the peripheral smear. Further assessment by flow cytometry confirmed the diagnosis of B-acute lymphoblastic leukemia, for which he was initiated on prednisolone at a dosage of 1 mg/kg/day. On the 15th day of therapy, he developed persistent cough. A computed tomography of the chest showed no evidence of pulmonary infection and steroids were continued. However, he developed rapidly worsening dyspnea on the next day and was referred to us for further evaluation. Initial evaluation revealed a heart rate of 150/min, blood pressure of 120/70 mmHg, and respiratory rate of 38/min. Examination revealed a normal jugular venous pulse with bilateral fine crepitations. Chest X-ray showed bilateral diffuse nodular opacities with no specific localization, but he could not be shifted for a high-resolution computed tomography (HRCT) scan of the chest due to tachypnea. Arterial blood gas analysis showed isolated hypoxia, and he was initiated on noninvasive ventilation (NIV) for the same. He was initiated on empiric broad-spectrum antibiotic coverage with meropenem, teicoplanin, and voriconazole, as he had been admitted in another multidisciplinary hospital for a week. His cough was predominantly nonproductive, and we were unable to obtain a sample for microbiologic analysis even after induction with 3% saline.

He had transient improvement in respiratory symptoms after 48 h, and an HRCT thorax was obtained. It revealed bilateral areas of nodularity and ground glassing along the pulmonary vasculature, indicating hematogenous dissemination. There were no other signs specific for a fungal infection. However, he developed a severe dry cough on the 3rd hospital day, and increased opacities were noted on chest X-ray. The initial blood culture isolated Gram-negative bacilli, which were identified as A. xylosoxidans by the VITEK-2 system. Antibiotic sensitivity was checked with the same system and showed sensitivity only to ciprofloxacin, levofloxacin, and minocycline. Antibiotics were modified, and levofloxacin and doxycycline were added, but he continued to clinically deteriorate. He developed worsening respiratory distress on NIV, but the family refused intubation and ventilation. He had progressively worsening respiratory failure, followed by a cardiac arrest.


  Discussion Top


BSIs are a common cause of mortality in patients with acute leukemia, with incidence ranging from 12% to 38% during treatment. Studies from Western literature have shown that up to 30% of mortality in acute leukemias can be attributed to BSIs, a number which may be as high as 40% in the Indian setting.[1] Data from pediatric leukemia cohorts in India have also shown a prevalence of 19% for BSI, Gram-negative infections being prominent. Ominously, over 87% of these isolates were seen to be resistant to carbapenems in vitro.[2] In most studies in patients with leukemia,  Escherichia More Details coli, Pseudomonas spp. and Klebsiella spp. continue to be the commonly isolated Gram-negative bacteria. A. xylosoxidans as a cause for febrile neutropenia with respiratory worsening is a rare finding.

Our patient demonstrates a rapidly worsening pneumonia with bilateral pulmonary involvement and respiratory failure with isolation of A. xylosoxidans in the blood culture. Achromobacteria are nonlactose-fermenting Gram-negative bacteria, ubiquitously found in soil and water. This group was first described in 1971 and is closely related to the Bordetella group. Two species such as xylosoxidans and denitrificans have been noted to cause disease in immunosuppressed populations.[3] Over the past two decades, it has been noted to cause BSI with significant mortality in patients with leukemia. Although considered an opportunistic pathogen, it has a number of traits which allow it to survive in nosocomial environments, including intravenous fluids and chlorhexidine solutions. Over 90% of BSI due to Achromobacter have been noted to be nosocomial in nature. The infection is most commonly seen to be transmitted from patient to patient through contact or inanimate surfaces.[4]

Achromobacter plays a significant role in colonization and infections in patients with cystic fibrosis (CF) or BSI in those with indwelling medical catheters. It is fast emerging as an important colonizer in patients with CF, and in certain populations, it has become as important as other common organisms including Burkholderia, Pseudomonas, and Hemophilus. Rarer manifestations include meningitis, endocarditis, cholecystitis, keratitis, and osteomyelitis. In the non-CF setting, hematologic and solid-organ cancers are noted to be the most common underlying comorbidities. A concise review by the American Thoracic Society notes that approximately 32 cases of respiratory infection with Achromobacter have been documented in non-CF patients so far.[3] Importantly, many of these patients had an underlying malignancy or a structural lung disease. Our patient presented with rapid onset of hypoxia, with bilateral pulmonary nodules and infiltrates developing over a period of 2 days. The same review also outlines that Achromobacter infections do not demonstrate a “typical” pattern on chest imaging, and like our patient, nodular opacities may be a common presentation. The first patient from India with Achromobacter pneumonia was reported in 2014 in a community-acquired setting and was successfully treated with 14 days of meropenem.[5] In the oncology setting, only two cases from India have been reported so far. The first reported patient developed a wound infection over a carcinoma breast recurrence, and the organism was isolated from wound swabs.[6] The second patient had carcinoma epiglottis and developed lower respiratory infection 3 months after chemotherapy and radiotherapy.[7] To the best of our knowledge, our patient is probably the third reported patient from India with this infection in an oncology setting.

Antibiotic sensitivity data for uncommon organisms would help to guide therapy once initial isolates are available. In general, Achromobacter has been found to be sensitive to piperacillin/tazobactam and carbapenems in vitro. Of the cephalosporins, ceftazidime has shown greater efficacy compared to other agents of this group. Fluoroquinolones are also found to be active, with gatifloxacin and levofloxacin being more active than ciprofloxacin. Most studies showin vitro resistance to penicillins, vancomycin, and aminoglycosides. However, many isolates, including ours, showed resistance to carbapenems, precluding the use of these agents as single-agent therapy. The results to colistin susceptibility are variable. Data from Danish CF patient registries has shown that colistin resistance is rising and seen in approximately 40% of patients as of 2016.[8] Evaluation of broad-spectrum antibiotics also revealed that only 44% of strains were susceptible to tigecycline and 28% to colistin.[9] A summary of studies assessing antimicrobial sensitivities of Achromobacter is listed in [Table 1].[10],[11],[12],[13]
Table 1: Summary of studies evaluating antibiotic susceptibly of Achromobacter spp.

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Our patient demonstrates three important points. First, he had a BSI with a rare and resistant organism, and to the best of our knowledge, only the third reported in a cancer setting in India. Secondly, novel organisms such as Achromobacter can have an 'atypical' presentation on chest imaging and may show nodules and bilateral infiltrates rather than typical consolidation noted with other bacteria. Third, MDR organisms should be suspected whenever a patient with acute leukemia has a history of being in contact with a hospital before the presentation. This is a common situation seen in referral hospitals. In patients who present with signs of sepsis, due to the high mortality associated with BSI during this period, it may be reasonable to evaluate the need to adopt a “de-escalation” approach on a case-to-case basis, depending on the severity of clinical presentation.

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

None.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA, et al. Acute myeloid leukaemia: Challenges and real world data from India. Br J Haematol 2015;170:110-7.  Back to cited text no. 1
    
2.
Subburaj D, Uppuluri R, Jayaraman D, Vellaichamyswaminathan V, Kandath S, Raj R. Combating blood stream infections during induction chemotherapy in children with acute myeloid leukemia: Single center results in India. Pediatr Blood Cancer 2017;64:10.1002/pbc.26517.  Back to cited text no. 2
    
3.
Swenson CE, Sadikot RT. Achromobacter respiratory infections. Ann Am Thorac Soc 2015;12:252-8.  Back to cited text no. 3
    
4.
Mody M, Quintiliani S, Patel PS, Migliore C, Anandarangam T. Oh No! Achromobacter. InB59. Bacterial Infection Case Reports 2019 May (pp. A3717-A3717). American Thoracic Society.  Back to cited text no. 4
    
5.
Aundhakar S, Mane M, Bharadiya A, Pawar S. Watch out! Pneumonia secondary to Achromobacter denitrificans. Ann Med Health Sci Res 2014;4:S22-4.  Back to cited text no. 5
    
6.
Eshwara VK, Mukhopadhyay C, Mohan S, Prakash R, Pai G. Two unique presentations of Achromobacter xylosoxidans infections in clinical settings. J Infect Dev Ctries 2011;5:138-41.  Back to cited text no. 6
    
7.
Roy P. Pulmonary infection caused by Achromobacter xylosoxidans in a patient with carcinoma of epiglottis: A rare case. J Clin Diagn Res 2014;8:DD01-2.  Back to cited text no. 7
    
8.
Pedersen MG, Olesen HV, Jensen-Fangel S, Nørskov-Lauritsen N, Wang M. Colistin resistance in Pseudomonas aeruginosa and Achromobacter spp. cultured from Danish cystic fibrosis patients is not related to plasmid-mediated expression of mcr-1. J Cyst Fibros 2018;17:e22-3.  Back to cited text no. 8
    
9.
Jacquier H, Le Monnier A, Carbonnelle E, Corvec S, Illiaquer M, Bille E, et al.In vitro antimicrobial activity of “last-resort” antibiotics against unusual nonfermenting Gram-negative bacilli clinical isolates. Microb Drug Resist 2012;18:396-401.  Back to cited text no. 9
    
10.
Gales AC, Jones RN, Andrade SS, Sader HS. Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative bacilli isolated from Latin America: Report from the SENTRY Antimicrobial Surveillance Program (1997-2002). Mem Inst Oswaldo Cruz 2005;100:571-7.  Back to cited text no. 10
    
11.
Sader HS, Jones RN. Antimicrobial susceptibility of uncommonly isolated non-enteric Gram-negative bacilli. Int J Antimicrob Agents 2005;25:95-109.  Back to cited text no. 11
    
12.
Barragán EP, Pérez JS, Corbella L, Orellana MA, Fernández-Ruiz M. Achromobacter xylosoxidans bacteremia: Clinical and microbiological features in a 10-year case series. Rev Esp Quimioter 2018;31:268-73.  Back to cited text no. 12
    
13.
Díez-Aguilar M, Ekkelenkamp M, Morosini MI, Merino I, de Dios Caballero J, Jones M, et al. Antimicrobial susceptibility of non-fermenting Gram-negative pathogens isolated from cystic fibrosis patients. Int J Antimicrob Agents 2019;53:84-8.  Back to cited text no. 13
    



 
 
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