Achromobacter xylosoxidans Bacteremia in a Liver Transplant Patient: A Case Report and Literature Review

Since the first isolation of Achromobacter xylosoxidans, it has been increasingly recognized as an opportunistic pathogen. It is an aerobic Gram-negative bacillus mainly found in aquatic environments. It has been reported to cause nosocomial infections, especially in immunocompromised patients. This organism has a unique susceptibility to antimicrobials, being resistant to most commonly used cephalosporins and aminoglycosides, with susceptibility to piperacillin/tazobactam and most carbapenems. In this case, we report a case of a 60-year-old female with a history of liver transplantation, who developed nosocomial Achromobacter xylosoxidans bacteremia complicated by septic shock, multi-organ failure, and death.


Introduction
Achromobacter xylosoxidans is a motile, aerobic Gram-negative bacillus that has been linked to severe infections in humans, mainly in immunocompromised individuals. Achromobacter xylosoxidans was first isolated and described by Yabuuchi and Ohyama in 1971 [1]. Although the first isolation by Yabuuchi and Ohyama was from ear discharges of patients with otitis media, it is widely believed that the organism is mainly found in aquatic environments and causes infections in immunocompromised individuals. Over the years, Achromobacter species have been linked to multiple outbreaks of nosocomial infections, especially in ICU settings. An example of such an outbreak is the cluster of cases of nosocomial Achromobacter infection in Kerala, India, which was found to be caused by contaminated furosemide ampoules [2]. Infections caused by the organism can vary, from pneumonia, bacteremia, meningitis, and device-related infections. Bacteremia is considered to be the most common. In one retrospective study, all Achromobacter species were susceptible to meropenem and piperacillin-tazobactam with resistance to aminoglycosides, aztreonam, and most of the cephalosporins [3].

Case Presentation
A 60-year-old female presented with a history of type 2 diabetes mellitus and chronic kidney disease secondary to diabetes. She had a history of liver transplantation at the age of 45 due to liver cirrhosis secondary to chronic Hepatitis C virus infection, treated successfully with a sustained virologic response.
The patient presented with vomiting and diarrhea for five days. The diarrhea was watery and occurred around 5-6 times per day, with no hematemesis or bleeding per rectum. The patient did not report any abdominal pain or fever. On the day of admission, the patient felt generalized weakness and dizziness followed by a fall but no loss of consciousness or abnormal movement. At home, she was taking Tacrolimus 0.5 mg daily. She was followed up regularly by the hepatology outpatient clinic and was taking her medications regularly.
On examination, the patient was clinically stable, fully conscious and oriented, afebrile, and had dry oral mucosa. Abdomen, respiratory, and cardiovascular examinations were unremarkable. Neurological examination was normal, and no focal findings were found.
Blood tests on admission showed evidence of acute kidney injury (worsening from her baseline) and high anion gap metabolic acidosis, with liver enzymes within normal limits ( Table 1).  She was admitted to the medial floor as a case of possible gastroenteritis and dehydration. Blood cultures, blood for cytomegalovirus (CMV) polymerase chain reaction (PCR), and stool for Clostridium difficile toxins along with stool culture were sent. She was started on IV ceftriaxone and metronidazole along with IV fluid resuscitation. Ceftriaxone and metronidazole were discontinued within 48 hours of admission as there was no evidence of infection.
Her stool workup revealed a positive Clostridium difficile positive PCR but was negative for Clostridium toxins; however, because the patient continued to have diarrhea, oral vancomycin for Clostridium difficile treatment was initiated.
Over the next few days, the patient's renal function continued to deteriorate, although she clinically remained stable and her diarrhea improved.
On the seventh day of the hospital admission, the patient became hypotensive and drowsy. New sets of blood cultures were sent and started empirically on piperacillin/tazobactam with the impression of the development of sepsis. As blood pressure failed to respond to IV fluid boluses and the patient showed evidence of hypoperfusion evident by a change in sensorium along with elevated serum lactate, she was admitted to the medical ICU and started on norepinephrine and vasopressin infusion. Blood culture revealed Achromobacter xylosoxidans, which was sensitive to piperacillin/tazobactam and meropenem ( Table 2).  As the patient's condition did not improve, antibiotics escalated to meropenem. Her condition deteriorated, and she developed multi-organ failure. She required intubation and mechanical ventilation. Unfortunately, she died 48 hours after ICU admission.

Discussion
Achromobacter xylosoxidans is a recognized pathogen in immunocompromised patients. Achromobacter xylosoxidans has low virulence but has been known to cause nosocomial infection, particularly in high-risk individuals [3,4]. In addition, many risk factors have been identified to increase the risk of infection by Achromobacter xylosoxidans, including immunosuppression, prolonged hospitalization, malignancy, neutropenia, and the presence of a central venous catheter [5].
Many healthcare-associated infections and outbreaks of Achromobacter xylosoxidans have been reported previously due to contaminated medical equipment and medications [2,6], and surgical site infections causing delayed surgical wounds have been described [7].
In the reviewed articles, the most common feature among the patients is an underlying malignancy. Infective endocarditis typically occurs in patients with valve replacement, although one case of infective endocarditis was reported in a healthy immunocompetent patient with a native valve [8]. One case report described a patient with pulmonary tuberculosis and Achromobacter xylosoxidans bacteremia, which was complicated by septic shock and death [9]. Table 3 highlights previous case reports of Achromobacter xylosoxidans.   * One patient developed more than one positive clinical isolate and may develop more than one hospital-acquired infection; ** Correctional cardiac surgery: interatrial and interventricular communication corrected at 11 months of age and aortic coarctation correction at age 10; *** The author concluded that the infected pleural effusion likely represents hematogenous dissemination; **** An environmental investigation concluded that a contaminated atomizer was the source of the outbreak.
Antibiotic sensitivity was consistent in the literature, with most strains resistant to cephalosporins, aztreonam, and aminoglycosides and being susceptible to piperacillin/tazobactam, meropenem, imipenem, and sulfamethoxazole-trimethoprim, with variable resistance to fluoroquinolones [3,10].
Our patient had multiple risk factors for developing severe infection given her age, comorbidities such as diabetes mellitus, chronic kidney disease, history of liver transplantation, and use of immunosuppressants along with hospitalization. It is worth mentioning that the initial blood cultures on admission were negative, thus concluding that the bacteremia was acquired during her hospital stay. Although the patient was started on the appropriate antibiotics even before the culture result, unfortunately, she developed multi-organ failure. She died within a few days of admission to the medical ICU.

Conclusions
In reviewing the available literature, it was concluded that Achromobacter xylosoxidans is an opportunistic pathogen that can cause serious nosocomial infection, especially in immunocompromised patients, which can be fatal. In our case report, the patient developed severe septic shock and did not respond to appropriate antimicrobial therapy, given her significant medical history. Therefore, awareness of this organism needs to be raised, especially given its antibiotic resistance pattern, which must be kept in mind when starting empirical therapy.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.