Case Report
Diabetic foot infection caused by Burkholderia cepacia complex: Report of an unusual case with a scoping literature review
https://doi.org/10.21203/rs.3.rs-1450067/v1
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published 05 Jun, 2022
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According to previous publications, Burkholderia cepacia complex (BCC) species are widely described pathogens in cystic fibrosis (CF) patients but not in individuals with diabetes mellitus (DM). We report a diabetic foot infection caused by BCC in a 42-year-old male patient who responded clinically after surgical debridement and meropenem monotherapy. In addition, a scoping review was constructed to map BCC infections in patients with DM.
Burkholderia cepacia complex
diabetic foot infection
noncystic fibrosis patients
The BCC is a universal nonglucose fermenter aerobic Gram-negative bacillus organized into no less than 20 phylogenetically strictly linked bacterial species recognized by the recA gene sequences 1. However, Burkholderia cenocepacia is considered the most virulent species for humans, with higher mortality rates than other Burkholderia spp., and usually causes recurrent respiratory infections in CF patients and is associated with healthcare-associated disorders 1.
The different BCC species are not common pathogens in skin and soft tissue infections (SSTIs) 2,3, even in diabetic patients, where polymicrobial flora is present in most cases 1,4. Therefore, we have decided to report the following issue because of the reported condition’s rarity, the threat that BCC may represent, and its intrinsic resistance to severe antimicrobials. In addition, a scoping review was conducted to map the relevant publications concerning the association between DM and BCC infection.
A 42-year-old male patient with type-2 DM (T2DM) presented to our emergency room (ER) in October 2018 with a soft tissue infection on the left foot sixteen days after a penetrating plantar injury caused by a piece of glass. He had sought the ER ate the same day as the plantar puncture wound and was submitted to surgical removal of the fragment of glass. Days before his first visit to the ER, he was barefoot in a muddy soccer field with rubbish and dog feces. Because of the small-fiber neuropathy, he did not notice the glass after the game. This penetrating injury likely occurred during the game practice since he was not barefoot at another time in the last few days. Two days after the trauma, the patient presented to the ER with intense pain, erythema and swelling on the plantar site. Then, the emergency physician prescribed a seven-day course of amoxicillin/clavulanate 875/125 mg PO BID plus ciprofloxacin 500 mg PO BID. Then, as there was no clinical improvement, the patient sought medical care for the third time and was hospitalized for evaluation by the vascular surgery team (VST). The wound was categorized as PEDIS 3 infection severity (PEDIS, P = perfusion, E = extent/size, D = depth/tissue loss, I = infection, S = sensation). The PEDIS 3 grade means a moderate infection; it extends under subcutaneous tissue, or erythema surpasses a 2-cm rim over the ulcer, and there are no systemic signs of infection 5.
On general examination, the mental status of the patient was preserved, the systemic blood pressure was 130/80 mm Hg, the heart rate was 97/min, the temperature was 36.4°C, and the respiratory rate was 16/min; the body mass index (BMI) was > 30 kg/m2. Laboratory tests at admission showed hemoglobin = 12.4 g/dL, white cell count = 10.700/mm3 (neutrophils, 73.2%; eosinophils, 1.9%; lymphocytes, 20.4%; monocytes, 4.2%), platelets = 304 x 103/mm3, glycemia = 119 mg/dL, creatinine = 0.72 mg/dL, and BUN = 10.27 mg/dL. Based on the abovementioned parameters, the VST decided on surgical approach: they performed a debridement and a decompressive fasciotomy; the main intraoperative findings were the presence of a mild and thick exudate, friable tissue, and inflammatory signs restricted to aponeurosis. Afterward, the VST started clindamycin 600 mg IV q6 h and ciprofloxacin 400 mg IV q12 h, but a new debridement was necessary due to the lack of clinical improvement – during the new operation, the infection was still restricted to the aponeurosis level.
Due to therapeutic failure after hospital admittance, an infectious disease clinic was consulted, and the VST started piperacillin/tazobactam 4.5 g IV q6/6 h in a 4-hour extended infusion (EI). After forty-eight hours, inflammation signs persisted. Then, an additional surgical approach was needed; right at that time, soft tissue culture results from the first surgical procedure came back, with the identification of Burkholderia cepacia group (VITEK® 2), which was only susceptible to meropenem (minimum inhibitory concentration (MIC) = 2, VITEK® 2), according to the Clinical and Laboratory Standards Institute (CLSI) on Antimicrobial Susceptibility Testing published in 2018 6. We then prescribed meropenem at 2 g IV q6 h in 3-hour EI after considering MIC = 2, BMI > 30 kg/m2, and microangiopathy as an impediment to reach a high probability of target attainment (PTA).
After 24 hours of the onset of meropenem, clinical improvement was evident. To check damaged tissue not accessible in previous surgical procedures, MRI of the foot was performed, and signs of osteomyelitis of the phalanges of the 3rd and 4th fingers, in addition to ulcerations and fistulous paths of the cutaneous, subcutaneous, and deep myoadipose tissues in the plantar region of the ante foot, were identified. Even so, we chose conservative treatment with 14 days of meropenem. At the end of the first year of follow-up, mild infections occurred, but amputation was not needed.
BCC infections range from mild to septicaemia, especially in patients with CF or chronic granulomatous disease. According to published scientific literature, BCC is not a common pathogen in DFI 7–10. The case presented rectifies the importance of collecting tissue samples for microbiologic diagnosis. It may be a unique chance to identify a rare microorganism in DFI, such as BCC, which proved to be aggressive and is naturally resistant to several antimicrobials. Our hospital protocol considers the following items for deciding antibiotic therapy and hospitalization: PEDIS severity classification, hospitalization in the last six months, antimicrobial therapy for any reason in the previous three months, and previous colonization/infection by a multidrug resistant microorganism. Uncommon pathogens are not contemplated by the protocol, except for an ongoing outbreak or endemic scenario where those are present. Regarding therapeutics, the choice for treating osteomyelitis for 14 days is graded as a moderate recommendation, according to the IWGDF 2019 update 11. Despite clinical improvement with meropenem in this case, in vitro studies demonstrated that the combination of two or three drugs is more effective than monotherapy 12–15. However, these positive outcomes came from in vitro investigations with BCC isolates from CF patients and cannot support double or triple-antibiotic associations over single therapy. Therefore, clinical trials concerning BCC infections are required to obtain a more solid evidence grade.
Due to the rarity of the case presented, a systematic search according to the Preferred Reporting Items for Systematic Reviews and Metanalyses (PRISMA) checklist was performed to address preceding relevant data regarding the relation between DM and BCC infections in non-CF patients 16. The systematic research was not recorded in the International Prospective Register of Systematic Reviews (PROSPERO), as scoping reviews do not meet the requirements for registration on the platform 17. A search was conducted throughout PubMed using search terms relevant to Burkholderia cepacia complex and diabetes mellitus. This study applied the MeSH terms in PubMed and Doc Title, Abstract, Keyword (TITLE-ABS-KEY) in Scopus (supplement) and included all types of papers, including case reports. The relevant titles and abstracts were added, except papers that addressed infections in individuals with CF. The presence of DM as an underlying condition (observational studies) or cases reporting infections caused by BCC in diabetic patients had their full texts included. Additionally, references cited in qualified studies were visually checked. Two investigators independently screened the records for eligibility based on titles and abstracts and assessed each study’s full text to extract meaningful data. Opinions from a third review author were sought to resolve arguments.
Out of 138 records identified (supplement), seven fulfilled the described criteria for inclusion, three were observational investigations, and four were case reports (Table 1). The most recent evidence is a retrospective cohort study that established DM as a risk factor for mortality but in univariate analysis 18. One retrospective study concerning the risk factors for mortality in DFI found BCC as a pathogen in two cases of SSTIs (2/401, 0.5%) 19; the other publications refer to two case reports of BCC’s SSTI and eye infections - observational study and case report 2,20–23 (Table 1). Therefore, only two cases of DFI by BCC are presented in our systematic search. The pyomyositis case report clarifies that the primary sites were the right thigh and right shoulder 2.
Regarding the ability of BCC to infect non-CF patients, a plausible hypothesis is a lineage infecting organs other than the lung since we did not determine the BCC species and its virulence factors 24. Although BCC is historically described as having low virulence, molecular epidemiology findings reveal that highly transmissible strains emerge unsystematically 2,25. BCC can produce prompt mutation and adaptation, and a complex genome is split into chromosomes 25. In addition, virulence elements may not be allocated equally through B. cenocepacia 26. In a cohort of patients with BCC bacteremia, the non-CF patients were at increased risk for 14-day mortality compared with those with CF. This investigation demonstrated a strong correlation between bacteremia produced by two strains of B. cenocepacia (genomovar III) and mortality. Undoubtedly, the most complicating factor in infections caused by BCC is its intrinsic resistance to several antimicrobials. Primary cellular resistance tools, along with membrane impermeability and drug extrusion through efflux pumps, provide extensive defense against distinct classes of antimicrobials. BCC species remain in part susceptible to ticarcillin, ceftazidime, quinolones, minocycline, tobramycin, meropenem, and trimethoprim/sulfamethoxazole 27.
In conclusion, there are insufficient data to define the risks of BCC infection in diabetic patients, including DFI. Hence, a detailed anamnesis and initial therapeutic failure are fundamental to considering BCC involvement.
Acknowledgments: We thank Dr. Roberto Muniz Júnior and the Laboratório de Microbiologia at Hospital Unimed Volta Redonda for all support.
Disclosure of interest
The authors report no conflict of interest.
Financial support
This research received no external funding.
Informed consent was obtained from the patient.
Table 1. Relevant studies concerning BCC infection in DM patients without CF.
|
Publication |
Study design |
BCC infection in a patient with DM |
|
Ku et al., 201118 |
Retrospective cohort study Clinical characteristics and laboratory parameters of twenty-seven patients with blood cultures positive for BCC. Outcome: Overall 28-day mortality |
DM was a risk factor for mortality in univariate analysis. |
|
Sen and Demirdal, 2020 19 |
Retrospective cohort study Objective: Risk factors for mortality in DFI |
BCC was a pathogen in two cases of SSTI (2/401, 0.5%) |
|
Fadini et al., 2005 20 |
Case report |
Deep neck abscess (SSTI) |
|
Saran et al., 2018 2 |
Case report |
Spread pyomyositis (SSTI) |
|
Pathengay et al., 2005 21 |
Case report |
Recurrent endophthalmitis caused by BCC |
|
Ibrahim and Yap, 2018 23 |
Case report |
BCC keratitis in an elderly patient |
|
Muda et al., 2018 22 |
Retrospective observational study Objectives: clinical presentation, systemic risk factors, source of infective microorganism, treatment outcomes, and prognostic indicators of endogenous endophthalmitis |
Endophthalmitis (1/120, 0.83%) |
CF cystic fibrosis, DM diabetes mellitus.
published 05 Jun, 2022
Read the published version in Revista do Instituto de Medicina Tropical de São Paulo →
posted
You are reading this older preprint version