Introduction
Ochrobactrum anthropi formerly known as Achromobacter Centres for Disease Control and Prevention (CDC) group Vd, is an oxidase-positive, non-fermenting, Gram-negative bacillus.1, 2 The genus Ochrobactrum belongs to the family Brucellaceae.3 The name Ochrobactrum is derived from the Greek ‘ochros’, meaning pale yellow; which is the characteristic colour of Ochrobactrum colonies. The genus Ochrobactrum comprises nine species, of which only three species, O. anthropi, O. intermedium, and O. pseudintermedium, have been reported to occur in clinical samples.4 Ochrobactrum anthropi has been found in environmental and hospital water sources and has pathogenic potential in humans.1, 4, 5 This aerobic organism has an ability to survive in antiseptic solution and to form biofilms, which may cause serious nosocomial infections.5 Even though it is considered to have low virulence, O. anthropi has been described as an emerging pathogen, causing severe infections in immunocompromised hosts, and in those with medical devices such as indwelling catheters and drainage tubes. 2, 5, 6, 7 O. anthropi is often misidentified or missed out by conventional diagnostic techniques, which calls for the need of automated methods for the accurate identification and antimicrobial susceptibility testing of this unusual organism. We, hereby, report a case of O. anthropi causing septicemia and pneumonia in elderly patient who was a known case of diabetes mellitus type 2 and chronic kidney disease, and was on regular haemodialysis. The authors gives an insight of clinical manifestations, diagnosis, and treatment of infections caused by this unusual opportunistic pathogen.
Case Report
A seventy-year-old female, resident of western Uttar Pradesh, was brought to emergency with the history of fever since last 5 days, and shortness of breath since 2 days. She was admitted with central venous catheter in situ. As per patient’s previous medical records and as stated by her relatives, she was a known case of diabetes mellitus type 2 since last 20 years, taking medications irregularly. She was also diagnosed as a case of advanced chronic kidney disease about six months back. She had been on regular haemodialysis, two times per week, done via a Permcath inserted in the right internal jugular vein. The last dialysis was done one week back in another private hospital, as mentioned in her records. On physical examination, patient was disoriented and febrile, having temperature of 1020F. Her blood pressure was 104/60 mm Hg, pulse rate was 112/minute, and respiratory rate was 32 breaths/minute and oxygen saturation was 86%. On auscultation, bronchial breath sounds and crackles were heard in both the lung fields. Immediately, patient was shifted to intensive care unit and was put on ventilator support. Prior to administration of antibiotics, blood samples were collected for culture from two different sites, peripheral vein and permacath at the right internal jugular vein. Thereafter, intravenous cefpodoxime-clavulanic acid combination was started. Arterial blood gas analysis revealed pH 7.326, pCO2 34.6 mm Hg, pO274.2 mm Hg. Blood samples were also sent for hematological and biochemical analysis. Haematological investigations revealed leucocytosis (16200/mm3) with 79% neutrophils and 21% lymphocytes. Haemoglobin was 11.2 gm/dl, platelet count was 94000 cells/mm3, erythrocyte sedimentation rate was 36 mm/hour. C-reactive protein was 25.6 mg/dl. Procalcitonin level was 1.4 ng/ml. Renal function tests revealed serum creatinine 2.5 mg/dl, blood urea 60 mg/dl, sodium 132 mEq/l, potassium 4.2 mmol/l, chloride 103mmol/l and calcium 0.81mg/dl. Random blood sugar was 216 mg/dl. Liver function tests were within normal limits. Initial x-ray chest and subsequent Computed tomography (CT) scan of chest (Figure 1) showed bilateral lower lobar pneumonia. Ultrasound abdomen of the patient revealed bilateral small kidneys with raised parenchymal echogenecity and loss of corticomedullary differentiation suggestive of medical renal disease (Figure 2). Blood culture was done by an automated BACTEC System (BD) as per the manufacturer’s instructions. After 18 hours of incubation, central line blood culture showed positive signal for microbial growth. The growth was identified by conventional methods such as Gram staining, colony characteristics, motility and the biochemical tests.6 Gram staining done from the blood culture bottle showed Gram negative bacilli with no specific arrangement. Subculture was done on 5% sheep blood agar and MacConkey’s agar. After 24 hours of aerobic incubation at 370C, colonies on sheep blood agar were circular, about 1mm in diameter, mucoid, greyish in colour with slight tint of yellow, low convex and with entire edge (Figure 3), and MacConkey’s agar showed non-lactose fermenting mucoid colonies (Figure 4). The isolate was motile, catalase positive and oxidase positive. It reduced nitrates to nitrites, utilized citrate, hydrolysed urea and was indole negative. It utilized glucose oxidatively on Hugh and Leifson’s oxidation fermentation media. The isolate gave an alkaline slant by no change in the butt reaction on triple sugar iron agar. The above findings and characteristics of our isolate were pinpointing the growth of an unusual non-fermenter. So, the isolate was further identified by an automated VITEK 2 system (Biomerieux, France). Identification and drug susceptibility of the isolate were performed using VITEK 2 GN card and VITEK 2 AST-N281 card; respectively. The isolate was identified as Ochrobactrum anthropi. It was susceptible to ciprofloxacin, aminoglycosides, trimethoprim-sulfamethoxazole and carbapenems but was resistant to penicillin, ampicillin, cephalosporins, combination of beta lactam and beta lactamase inhibitor antibiotics, chloramphenicol, tetracycline and colistin.The peripheral line blood culture showed positive signal three hours later than the central line blood culture, suggesting a catheter-related bloodstream infection (CRBSI). The peripheral line blood culture also grew O. anthropi with similar antibiogram. The clinician was informed about the blood culture and the antibiotic sensitivity report on the fourth day following sample submission. The patient’s fever and respiratory distress had not subsided by that time and the repeat x-ray of chest showed no improvement. Based on the sensitivity report, patient was started on intravenous ciprofloxacin and meropenem. The central venous catheter was removed. After 7 days of treatment with these antibiotics and removal of the catheter, the patient became afebrile and her respiratory distress improved. For follow-up, after one week of treatment, a fresh blood sample was drawn for culture, and this showed no growth at 37°C after 5 days of aerobic incubation. Follow-up x-ray of chest showed resolution of consolidation. Patient recovered and was extubated after 12 days of treatment. She was then shifted to ward. She was accepting orally and was able to maintain her oxygen saturation between 96-98%, without oxygen support. Finally, after two weeks patient was discharged with good general condition.
Figure 1
Computed tomography (CT) scan of chest showing bilateral lower lobar consolidations with air bronchograms.
Discussion
Ochrobactrum anthropi is an aerobic, motile, urease positive, non-fermenting gram-negative bacillus with strict oxidative metabolism.1, 6 In recent years it has gained importance as an emergent pathogen in immunocompromised patients, especially in hospital settings, as it can survive within intravenous fluids and dialysis liquids.2, 6, 7 It is ubiquitous in nature, belonging to the Brucellaceae family, within the Alphaproteobacteria class.7, 8 O. anthropi has been isolated from a number of environmental sources, and also recovered from various clinical samples, especially blood. It has been associated primarily with bacteremia and sepsis, especially in cases involving infected indwelling catheter lines.2, 9, 10, 11 Although initially believed to be an opportunistic pathogen causing infections in severely-ill or immunocompromised patients, especially the catheter-related blood stream infections, O. anthropi is increasingly being recognized as a pathogen in immunocompetent hosts which have been found to be associated with osteomyelitis, pelvic abscess, prosthetic valves, trauma, endophthalmitis, and usage of contaminated pharmaceuticals.2, 10, 11 The predisposing factors such as prolonged antibiotic usage, steroid therapy, prior surgical procedure with allografts, accidental wound, and co-infection with other bacterium have been seen to be implicated with O. anthropi infections.2 The correct identification of O. anthropi is a diagnostic challenge. It resembles the Pseudomonas species in that it has affinity for acquatic sources. It is generally mis-identified as Pseudomonas or Brucella by conventional culture methods.3, 5 Our case report highlights the role and importance of automated culture methods for the rapid and an accurate identification of this rare pathogen up to species level, so that it is not missed out in routine microbiological practice. O. anthropi poses a significant nosocomial threat, and has unique antibiotic susceptibility profile. Therefore, antimicrobial susceptibility testing done using automated system and alerting the treating clinician has resulted in saving the life of our patient. In our case, indwelling catheter lines had been the main underlying cause for septicaemia, as O. anthropi can adhere to catheters or other medical devices. Thus, breach in sterile clinical practices and instrumentation becomes the culprit for the nosocomial potential of O. anthropi causing blood stream infections. Our isolate was susceptible to ciprofloxacin, aminoglycosides, trimethoprim-sulfamethoxazole and carbapenems but was resistant to penicillin, ampicillin, cephalosporins, combination of beta lactam and beta lactamase inhibitor antibiotics, chloramphenicol, tetracycline and colistin. It was found to be AmpC beta lactamase producers, similar to the observations made by other studies.3, 5 Acquired resistance of O. anthropi to colistin, which had been seen in our case, was also found in the studies done by Khan ID et al.5 and Menuet M et al.12 In 2016, Ashraf F9 describes a case of O. anthropi - induced septic shock and infective endocarditis in a patient of end- stage renal disease, who was on haemodialysis, and also had a pacemaker for third degree heart block. Ashraf F9 observed that his patient responded to intravenous meropenem, and on transoesophageal echocardiogram native mitral valve infective endocarditis was detected which got managed with antibiotic therapy for 6 weeks. Thus, patient with blood culture positive for O. anthropi should be screened for endocarditis, especially those who have any hardware in their heart such as prosthetic valves and pacemakers.9 In 2013, Siti Rohani AH et al.13 have also reported O. anthropi catheter-related bacteremia in a diabetic and hypertensive patient with end stage renal failure, who was on regular haemodialysis. O. anthropi isolated by Siti Rohani AH et al.13 was found to be sensitive to imipenem, meropenem, cefepime, amikacin, gentamicin, ciprofloxacin and trimetroprim-sulfamethoxazole, and resistant to ceftazidime, piperacillin-tazobactam and polymyxin-B. Our case findings are similar to the observations made by Siti Rohani AH et al.13 A study carried out by Daxboeck F et al.14 reported bacteremia with O. anthropi in patient on haemodialysis, who had responded by removal of the dialysis catheter and a 3-week course of gentamicin. Chertow GM has also reported catheter-related blood stream infection due to O. anthropi in a haemodialysis patient.15 Given the organism's hydrophilic property and the usage of indwelling catheters in debilitated patients with renal failure, O. anthropi infection should be considered in the differential diagnosis of a haemodialysis patient with unexplained fever.15 A study carried out in Amritsar by Arora U et al. 16 have reported a case of O. anthropi septicaemia in an elderly male patient with a history of hypertension, diabetes and coronary artery disease with severe left ventricular dysfunction, who had undergone intraaortic balloon pump insertion, following which the patient developed a haematoma at the local site, which had led to blood stream infection. Catheter-related blood stream infection (CRBSI) due to O. anthropi have been documented by Kern WV et al. 17 in patients of acute leukemia as the underlying disease. The Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection 18 states that “A definitive diagnosis of catheter-related blood stream infection requires that the same organism grow from at least one percutaneous blood culture and from a culture of the catheter tip, or that two blood samples be drawn (one from a catheter hub and the other from a peripheral vein) that, when cultured, meet CRBSI criteria for quantitative blood cultures or differential time to positivity.” In 2013, a study done in New Delhi by Kumar S et al.19 reported a case of O. anthropi septicaemia and pneumonia in a preterm infant with congenital anomalies, who had responded well and recovered with meropenem administered for seven days. In our case also, after treatment with intravenous meropenem and ciprofloxacin patient became afebrile, follow-up blood culture was sterile and the follow up chest X-ray showed resolution of consolidation. In 2013, Naik C et al.2 documented a case of septic shock and respiratory failure from pneumonia secondary to O. anthropi infection, who had recovered with intravenous ciprofloxacin. Cieslak TJ et al.20 had reported a case of pneumonia due to O. anthropi in a patient with underling lung carcinoma, where this rare pathogen was isolated on culture from the purulent discharge from the draining chest tube, and the patient had responded well to trimethoprim-sulfamethoxazole administered via gastrostomy tube. The various authors across the world has reported O. anthropi blood stream infections in immunocompromised patients.5, 13, 15, 16, 17, 19, 21, 20 However, in 2017, Rastogi N et al.22 observed catheter-related septicaemia with meningitis due to O. anthropi, in an elderly immunocompetent male with a head trauma. Kettaneh A et al.23 documented a case of septic shock that occurred in an otherwise healthy host after administration of a peripheral venous infusion of a solution contaminated with O. anthropi. Our case report alerts the emergence of O. anthropi as an opportunistic pathogen in an immunocompromised patient. Severe immunosuppresion and association with an indwelling catheter appears to be the major factors favouring the O. anthropi septicaemia. Treatment of O. anthropi infection is challenging because of widespread and unpredictable resistance to antimicrobial agents. Timely initiation of appropriate antibiotic therapy and removal of catheter played a key role to favourable clinical outcome in our case.
Conclusion
The authors stress upon the importance of rapid identification and susceptibility testing of Ochrobactrum anthropi, as this unusual and unconventional organism appears to be an emerging opportunistic and nosocomial pathogen associated with the implantation of intravenous catheters or other medical devices in immunosuppressed or debilitated patients. This case also highlights the importance of prompt communication between microbiologists and clinicians in managing the infection, in view of O. anthropi unique antibiotic susceptibility profiles. Implementation of effective methods of sterilization and strict adherence to infection prevention and control practices becomes essential to prevent the spread of this organism.
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