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2013

AOPXXX10.1177/1060028013500942Ponnapula et alThe Annals of Pharmacotherapy

Case Report

Treatment of Rhizobium radiobacter Bacteremia in a Critically Ill Trauma Patient

The Annals of Pharmacotherapy 47(11) 1584­–1587 © 2013 SAGE Publications Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013500942 aop.sagepub.com

Supriya Ponnapula, BS1, Joseph M. Swanson, PharmD, BCPS1, G. Christopher Wood, PharmD, FCCP1, Bradley A. Boucher, PharmD, FCCP, FCCM1, Diana L. Wells, PharmD2, Martin A. Croce, MD1, and Timothy C. Fabian, MD1

Abstract Objective: To report the first case of Rhizobium radiobacter bacteremia in a critically ill trauma patient. Case Summary: A 36-year-old female trauma patient hospitalized at The Regional Medical Center at Memphis developed bacteremia due to Rhizobium radiobacter on hospital day 9. The central line catheter tip culture from the same hospital day was negative. No source for the R radiobacter bacteremia was identified. Empirical and definitive antibiotic therapy consisted of cefepime 2 g intravenously every 8 hours for at total of 8 days. On completion of antibiotics, the patient demonstrated clinical resolution by immediate defervescence and gradual normalization of her white blood cell count. She demonstrated microbiologic success of therapy with negative blood cultures on hospital days 22, 34, 45, and 61. She was discharged on hospital day 80. Discussion: Rhizobium species are common soil and plant pathogens that rarely cause infections in humans. Previous reports of Rhizobium infections have been in immunocompromised patients; generally those with cancer or HIV infection. Intravenous catheters have commonly been cited as the source of infection. The trauma patient in this case constitutes a unique presentation of R radiobacter bacteremia when compared with other case reports. Her indwelling catheter was not the source of her infection, and her only identifiable risk factor for R radiobacter infection was hospitalization. However, she did possess potential reasons for development of an infection with an unusual organism such as R radiobacter. Potential immune modulating therapies included blood transfusions, opioid analgesics, benzodiazepines, general anesthetics, and surgical procedures. Finally, trauma itself has been associated with some degree of immunosuppression. All these issues may have placed the patient in this case at risk of an opportunistic infection like R radiobacter. Conclusion: Based on this case, R radiobacter may be considered a potential pathogen causing bacteremia in critically ill trauma patients. Keywords critical care, infectious disease, bacteremia, trauma, Rhizobium spp

Introduction Rhizobium species are common soil and plant pathogens that rarely cause infections in humans. The genus Rhizobium is a new classification that includes the former genera Agrobacterium and Allorhizobium.1 Organisms of this genus are aerobic, motile, non–spore forming, oxidase and catalase positive, gram-negative bacilli that demonstrate variable susceptibility to antibiotics.2 Found globally, most species of these opportunistic plant pathogens contain tumor-inducing plasmids, which cause neoplastic growth in several species of plants.2 Although most isolates of Rhizobium are of low virulence to humans, there are case reports of R radiobacter and

R tumefaciens causing clinically significant infections. The majority of these infections were caused by R radiobacter, involved foreign devices, and occurred in immunocompromised patients with HIV infection or malignancy. This case report describes the treatment of R radiobacter bacteremia

1

University of Tennessee Health Science Center, Memphis, TN, USA Auburn University, Auburn, AL, USA

2

Corresponding Author: Joseph M. Swanson, PharmD, BCPS, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Suite 203, Memphis, TN 38163, USA. Email: [email protected]

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Ponnapula et al in a critically ill trauma patient. This is the first such report to our knowledge.

Case Report A 36-year-old Caucasian woman was admitted to the Presley Memorial Trauma Center at the Regional Medical Center at Memphis after a motor vehicle collision. The collision caused the following injuries: splenic and liver lacerations, left kidney infarction, right internal carotid artery pseudoaneurysm, degloving injury and multiple fractures of the left hand, left radial and ulnar shaft fractures, left lower extremity open ankle fracture, comminuted public symphysis and sacral fractures, bilateral occipital condylar fractures, sternal fracture, pneumomediastinum, bilateral pneumothoracies, and multiple rib fractures. Past medical history was significant for hypertension, but the patient was not taking her medication for this condition. The patient was 5 ft 7 in. tall and weighed 63.5 kg (103% of ideal body weight). Social history was positive for occasional alcohol use and negative for smoking and illicit drug use. Family history was not obtained. The patient was admitted directly to the trauma intensive care unit, where over the course of 6 weeks she underwent multiple surgeries, including a splenectomy, hepatorrhapy, tracheostomy, percutaneous angioplasty, percutaneous endoscopic gastrostomy, and multiple procedures for her left hand and ankle fractures. On the hospital day 1, she was placed on mechanical ventilation and received 9 units of packed red blood cells, 2 units of cryoprecipitate, 10 units of fresh frozen plasma, and 20 units of platelets. Prophylactic intravenous antibiotic therapy with cefazolin 1 g intravenously every 8 hours was started on hospital day 1, based on the patient’s estimated creatinine clearance (Est CLCr) of 78 mL/min (Cockroft-Gault), and completed on day 3, which was also the nadir for her decline in Est CLCr to 52 mL/min. By hospital day 8, the patient’s Est CLCr had returned to baseline (serum creatinine = 1 mg/dL, Est CLCr of 78 mL/min) and remained there for the duration of her hospitalization. During the first week, the patient completed the majority of the required surgeries for her injuries. On hospital day 3, the patient’s white blood cell count (WBC) increased from 11.0 × 103 to 17.5 × 103 cells/mm3. However, she remained afebrile. On day 5, her temperature, measured from her urinary catheter, escalated to 101.2°F (38.4°C). Blood and urine cultures were obtained, but were negative. On hospital day 8, her WBC count was 17.3 × 103 cells/mm3, and blood cultures were again drawn. On hospital day 9, the cultures were reported to have Gram-negative bacilli growing in 1 of 4 bottles. Based on the Gram stain, antibiotic therapy with cefepime was started. Cefepime dosing of 2 g intravenously every 8 hours was based on the patient’s Est CLCr of 78 mL/min. The final report for the blood cultures identified the pathogen as R radiobacter

growing in 1 of 4 bottles. The catheter tip from her central line was sent for culture on the same day as the blood cultures (hospital day 8), but no growth was noted. Additionally, a bronchoalveolar lavage obtained on day 9 demonstrated insignificant growth, ruling out ventilator-associated pneumonia as a source of the bacteremia. R radiobacter growing from the blood culture was susceptible to sulfamethoxazole/ trimethoprim, ceftriaxone, cefepime, imipenem, ciprofloxacin, gentamicin, tobramycin, and amikacin. It was intermediately susceptible to ampicillin/sulbactam, and resistant to ampicillin and piperacillin/tazobactam. Based on these data, the patient’s normal kidney function, and a review of the literature noting mostly broad-spectrum antibiotic therapy for treatment of R radiobacter bacteremia, definitive antibiotic therapy with 2 g of intravenous cefepime every 8 hours was continued. The patient responded well to therapy, did not experience hemodynamic compromise, and no adverse effects were identified. Clinical improvement was noted after completion of 8 days of antibiotic therapy. The patient’s temperature normalized during therapy; however, her WBC remained elevated, which prompted investigation for another infection. Multiple cultures (blood, urine, and pulmonary) and imaging were performed. All cultures were negative except on hospital days 21 and 44, when urine cultures revealed growth of ≥100 000 cfu/mL Candida albicans and Acinetobacter baumannii, respectively. The C albicans was successfully treated with fluconazole and the A baumannii with cefepime. Following completion of antibiotics, the patient’s temperature and WBC count returned to normal. Importantly, blood cultures taken on hospital days 22, 34, 45, and 61 were negative, and the patient did not experience another episode of bacteremia. The patient was subsequently discharged after 80 days in the hospital.

Discussion Rhizobium radiobacter is a common environmental bacterium. Clinical isolates in humans are rare (approximately 40 documented cases)3 but can cause many different types of infections such as cellulitis, peritonitis, bacteremia, urinary tract infection, and endocarditis.4 The majority of patients in these cases were immunocompromised, with HIV infection or malignancies accounting for a significant portion (up to 70%) in published reports.1,5-9 None of these reported cases involved critically ill trauma patients. Based on the literature, major risk factors for R radiobacter infection are suggested to be leukopenia, neutropenia, low CD4+ lymphocyte count, hospitalization, concurrent AIDS-related complications, as well as indwelling catheters and instrumentation.4 The critically ill trauma patient reported in this case is a unique presentation of R radiobacter bacteremia when compared with other case reports. Major risk factors for R radiobacter infection only included hospitalization and

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intravenous catheter use. However, the negative catheter tip culture taken on the same day as her positive blood cultures suggests this was not the source, and thus she only had the one risk factor of hospitalization. Trauma patients are generally immunocompetent prior to their injury and many have insignificant past medical histories, as was the case with this patient. Previous cases generally described patients with long-standing immunosuppression. The patient in this report did not receive any classical immunosuppressive medications during her stay. However, the patient in this report did possess potential reasons for development of an infection with an unusual organism such as R radiobacter. She was traumatically injured in motor vehicle collision, and received 9 units of blood and other blood products during her initial resuscitation. This was followed by numerous surgical procedures during her first week of hospitalization. Finally, she required the use of opioids for pain control and benzodiazepines for sedation while mechanically ventilated. Trauma,10-12 surgery,13 transfusions,14,15 and medications16-19 have all been noted to cause immunosuppression. As such, it is possible that the combination of these factors contributed to put the patient at risk of an opportunistic infection like R radiobacter. Since this patient had traumatic injuries and a clinical course similar to many other trauma patients, we reviewed our unit-specific culture database to determine if this organism had previously caused infections in the trauma intensive care unit. No other infections caused by Rhizobium spp, Agrobacterium spp, or Allorhizobium spp were recorded in the past 15 years (1997 through 2012), making this a unique case and raising the question as to why this patient developed this infection. One possibility is that this was a false positive culture result caused by contamination of laboratory saline solution. Such contamination has been previously reported and was discovered when it is was found that the R radiobacter isolates all had the same antimicrobial susceptibilities and electrophoretic fingerprints.20 However, it is highly unlikely that the isolate in the current case was due to contamination of the blood culture because the patient’s symptoms were consistent with bacteremia, resolved with antibiotic treatment, and no other patients in the hospital developed R radiobacter infections during this time. No other testing was conducted to determine if the patient was immunosuppressed (eg, HIV test), because trauma, analgesics, sedatives, anesthetics, and surgeries were deemed to have caused enough relative immunosuppression in this patient to result in the infection. This case suggests that R radiobacter can cause infection in trauma patients who do not have any classic immunocompromised conditions. Fortunately, R radiobacter is not usually highly drug resistant, but the reported antibiotic susceptibility patterns of this organism have been variable.1,5,7,8,21,22 R radiobacter has been universally reported as susceptible to fluoroquinolones, carbapenems, and cefepime.1,3-9,21 The organism has

variable susceptibility to third-generation cephalosporins (including ceftazidime), aminoglycosides, and sulfamethoxazole/trimethoprim.1,3-9,21 In all cases that reported susceptibilities to aztreonam, the isolates have been resistant.1,3,8,21 It is important to note that nearly all reports have described isolates that are susceptible to piperacillin/tazobactam,1,3-8 except for one that only reported resistance to piperacillin.21 The isolate described in this report was resistant to piperacillin/tazobactam, and is first reported isolate with such a resistance profile. This highlights the need to closely evaluate the susceptibilities of each R radiobacter isolate. A variety of antibiotics have been used successfully in different patient populations. Monotherapy with fluoroquinolones, beta-lactam/beta-lactamase inhibitors, third-generation cephalosporins, imipenem, and sulfamethoxazole/ trimethoprim are commonly reported.4 However, some reports describe the use of combination therapy with betalactams plus aminoglycosides1,5 or imipenem plus sulfamethoxazole/trimethoprim.4 The empiric use of cefepime in this patient was for broad Gram-negative coverage consistent with current clinical pathways in our intensive care unit. Cefepime was continued as definitive therapy primarily because the isolate was sensitive to that agent and the patient was responding well.

Conclusion Most infections caused by R radiobacter have been reported in patients with HIV, malignancy, or an immunocompromised state. However, our critically ill trauma patient presented with R radiobacter bacteremia and no previously identifiable immunocompromised condition. Based on this case, R radiobacter may cause bacteremia in critically ill trauma patients. Authors’ Note This case was presented at the 2012 ASHP (American Society of Health-System Pharmacists) Midyear Meeting and Exhibition, Las Vegas, Nevada, December 2-6, 2012.

Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Treatment of Rhizobium radiobacter bacteremia in a critically ill trauma patient.

To report the first case of Rhizobium radiobacter bacteremia in a critically ill trauma patient...
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