Bacillus pumilus cellulitis with bacteremia in a person who injects drugs, living with HIV–HCV co-infection: a case report

Abstract

Bacillus pumilus (B. pumilus) is a ubiquitous spore-forming bacteria that has rarely been implicated in extraintestinal infections, mostly in immunocompromised hosts. The authors report a case of B. pumilus cellulitis with bacteremia in a person who injects drugs living with human immunodeficiency virus–hepatitis C virus (HIV–HCV) co-infection. Although similar cases have been reported for some species of the genus, namely Bacillus anthracis (B. anthracis) and Bacillus cereus (B. cereus), this case reinforces the importance of considering other Bacillus spp. as potential pathogens in skin and soft tissue infections and bloodstream infections related to intravenous drug use.

Introduction

With the notable exception of the infamous Bacillus anthracis (B. anthracis), Bacillus spp. is a genus of saprophytic, aerobic or facultatively anaerobic, Gram-positive or Gram-variable rod-shaped bacteria with ubiquitous distribution. Due to their spore-forming ability, they can survive in the environment for long periods and withstand extremes of temperature. Despite accounting for as much as 1 % of all isolates in blood cultures, they are regarded as pathogens in less than a tenth of these [1]. Although generally overlooked, this genus is capable of causing serious and often fatal infection, especially in immunocompromised hosts.

Bacillus pumilus (B. pumilus) is part of the Bacillus subtilis group [2] and has rarely been reported as a human pathogen. Akin to Bacillus cereus (B. cereus), but to a much lesser extent, it has been associated with mild and self-limited foodborne illness caused by consuming toxin-contaminated foods [3, 4]. Its association with invasive infections seems to be even rarer, with only 17 cases reported to date, including primary bloodstream infection [5–8], catheter-related bloodstream infection [1, 5, 9], skin and soft tissue infection [10, 11], septic arthritis/osteomyelitis [12, 13], foramen ovale patch endocarditis [14] and gastroenteritis-related bacteremia [15]. Of these, eight occurred in immunocompromised hosts. Currently, the virulence factors of B. pumilus are still poorly understood, but they seem to include the production of cytopathic and haemolytic toxins, lecithinase and proteolytic enzymes [4, 16], as well as the ability to colonize the gastrointestinal tract of mammals [17].

We report a case of B. pumilus cellulitis with bacteremia after injection with contaminated drugs/paraphernalia in a person who injects drugs living with human immunodeficiency virus-hepatitis C virus (HIV–HCV) co-infection.

Case

A 44-year-old homeless man with no known medical or surgical history except current intravenous (IV) use of cocaine and heroin was admitted to the emergency department with pain and swelling on his right hand in the past 24 h, after an unsuccessful injection in a hand vein. On examination he was emaciated, febrile and had extensive erythema and oedema in the dorsum of his right hand and distal forearm. Other than that, his physical examination was unremarkable with a blood pressure of 112/68 mmHg. He had a microcytic and hypochromic anaemia (Hb 10,3 g dl⁻¹), neutrophilic leukocytosis (25220 /µl) and marked elevation of the C-reactive protein (306 mg l⁻¹). HIV serology was positive, with a CD4 +count of 898 /µl and viral load of 3680 ml⁻¹; HCV serology was also positive, with a viral load of 2500 IU ml⁻¹, but there was no biochemical or imaging evidence of hepatitis or cirrhosis. One set of blood cultures was drawn before the patient was started on empirical antimicrobial therapy with piperacillin/tazobactam and vancomycin and fluids. Since there was no purulent discharge, we did not sample the skin lesion for microbiological study. In the next 24 h the local inflammatory signs worsened, with extensive bullae forming on the epidermis (Fig. 1). A CT scan showed extensive oedema of the soft tissues and extensor tendonitis but no evidence of myositis and an ultrasound of the wrist excluded radiocarpal arthritis. After 41.7 h of incubation, one vial from the blood culture set was flagged as positive and the microscopic examination of the smear by Gram stain revealed the presence of large, ‘box-car’-shaped Gram-positive rods with squared-off ends and parallel sides (Fig. 2). At this time, the result was interpreted as a probable contamination, and an additional set of blood cultures was drawn. After 89.9 h of incubation, one vial from the second blood culture set was also flagged as positive and the microscopic examination of the smear by Gram stain was identical. After 24 h of incubation at 35±2 °C in 5 % CO₂, the subculture in chocolate agar revealed the presence of medium sized, opaque, grey colonies (Fig. 3), which were then identified by MALDI-TOF MS on VITEK MS (bioMérieux) as B. pumilus. Antimicrobial susceptibility testing (AST) was performed by the Kirby–Bauer method and interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) [18] clinical breakpoints for the genus Corynebacterium, as at the time there were no specific cut-offs for the genus Bacillus. The strain proved to be susceptible to tetracycline, ciprofloxacin and vancomycin and resistant to penicillin G and clindamycin. By the third day of treatment, the patient was afebrile, C-reactive protein was decreasing, and the skin lesions progressed to epidermal necrosis and shedding, with healthy skin underneath. Transthoracic echocardiography showed no valvular vegetations or insufficiency, and as subsequent blood cultures were negative, transesophageal echocardiography was not performed. He received 14 days of targeted antimicrobial therapy with vancomycin with gradual resolution of local inflammatory signs and CRP levels, and on discharge the skin on his hand was completely epithelialized with no necrotic or bullous changes. Despite being offered commitment to a drug treatment programme, he abandoned it and missed his follow-up consultation.

Fig. 1.

Photograph of the patient’s hand after 24 h of antimicrobial therapy.

Fig. 2.

Microscopic examination of the blood smear by Gram stain showing large, ‘box-car’-shaped Gram-positive rods with squared-off ends and parallel sides.

Fig. 3.

Macroscopic appearance of B. pumilus colonies in chocolate agar after 24 h of incubation at 35±2 °C in 5 % CO2.

Discussion

Only three cases of skin and soft tissue infection by B. pumilus have been previously reported [10], all in patients with direct contact with sheep, with lesions akin to cutaneous anthrax, namely a serohemorrhagic blister, surrounded by extensive oedema of the fingers and followed by cutaneous necrosis. Only one of the patients had systemic symptoms, and no involvement of other organs systems was noted, with B. pumilus being isolated from the blister fluid. Two patients were treated with amoxicillin-clavulanate 500/125 mg 3id for 10 days, the other with ciprofloxacin 750 mg bid for 30 days, with complete resolution. The AST of these strains was not reported.

Subcutaneous, intramuscular and intravenous drug use is a well-known risk factor for skin and soft tissue infections, including those by spore-forming bacteria [19]. Although previously regarded as occupational hazards associated with the manipulation of contaminated animal products, B. anthracis and B. cereus have recently been implicated in severe skin and soft tissue infections related to intravenous drug use [19]. B. anthracis [20, 21] has been so closely associated with intravenous drug use that the term ‘intravenous anthrax’ was coined after an outbreak in Europe in 2009–2014. In a German report of three cases of B. anthracis infection [20], two patients presented with severe multisystem disease (one with fulminant septic shock, dying within 24 h of hospital admission; another with severe skin changes requiring surgical debridement, pneumonia and pleural effusion) and the last one with systemic symptoms and localized skin and soft tissue infection. A report from the Health Protection of Scotland [21] identified 47 confirmed cases of intravenous anthrax with a 27 % mortality rate, although the clinical presentation and treatment were lacking. On the other hand, B. cereus infection has also been associated with intravenous drug use [19, 22, 23], mostly bacteremia with one case of cellulitis after injection [23] describing deep subcutaneous inflammation with gas bubbles, akin to gas gangrene, requiring surgical debridement. The association between Bacillus spp. infection and intravenous drug use is probably due to contamination of the drugs themselves or the injection paraphernalia [20, 21].

To the best of our knowledge, this is the first case reporting a B. pumilus invasive infection in an HIV–HCV co-infected patient, also being the first case linked to intravenous drug use. The clinical presentation in our case was relatively benign, possibly reflecting the low virulence of B. pumilus, the prompt initiation of antimicrobial therapy and the relatively good immune status of our patient, afforded by a high CD4 +count and absence of cirrhosis. The extensive local changes were probably due to the accidental delivery of the contaminated drug to the subcutaneous tissue and possibly to the production of a dermonecrotic factor, as hypothesized in a previous report [10]. Despite the results of the AST, clindamycin should probably still have been considered as adjunctive therapy due to its inhibitory effect on toxin synthesis.

Our case highlights that Bacillus spp. should not be automatically discarded as blood culture contaminants, especially in immunosuppressed patients and probably those with specific risk factors such as intravenous drug use and foreign medical devices. The distinction between contamination and infection might be challenging but true bacteremia is more likely if these bacteria are isolated from both vials of a single blood culture set or from several blood culture sets. As demonstrated through our case, newer microbiological diagnostic methods, such as MALDI-TOF MS, are very useful in differentiating among species of Bacillus spp., thus avoiding the use of specialized molecular methods. An important point to make is that, despite the extremely low prevalence of anthrax in our country, if this had been such a case, the risk of occupational exposure to laboratory workers would have been high and thus, the isolation of Gram-positive rods in patients that use intravenous drugs should prompt the appropriate protection measures. Another highlight from our case is that the local inflammatory and necrotic changes associated with Bacillus sp. infection acquired through drug injection may be severe, and these patients should be approached with care in a centre where imaging methods and surgical consultation are available.

In conclusion, Bacillus species should not automatically be disregarded as contaminants in the setting of skin/soft tissue or bloodstream infection in persons using intravenous drugs, their isolation should prompt repeat cultures and appropriate protection measures of hospital/laboratory staff until species identification. Due to the pathogenicity of this genus, local and systemic changes should be closely monitored during treatment.