Brucella anthropi & intermedia Infections: Saudi Arabia Case Series

Emerging Brucella Species Pose Diagnostic Challenges in Saudi Arabia

A recent case series highlights the increasing, yet often overlooked, threat of Brucella anthropi and Brucella intermedia – rare but emerging healthcare-associated pathogens – and the diagnostic confusion they create due to recent taxonomic shifts within the Brucella genus. The study, the first of its kind in Saudi Arabia, underscores the need for heightened awareness and improved diagnostic accuracy, particularly in regions where traditional brucellosis remains prevalent.

The reclassification of these organisms, formerly known as Ochrobactrum, into the Brucella genus has created a critical challenge for clinicians. Reports indicate potential misidentification of both Ochrobactrum and brucellosis-causing Brucella species, and vice versa [15, 16]. This ambiguity is particularly concerning given the differing clinical implications and treatment approaches for these distinct groups.

Distinguishing Between Brucella Species: BBS vs. NBBS

The Centers for Disease Control and Prevention (CDC) has differentiated between Brucellosis-Causing-Brucella Species (BBS) – including Brucella canis, B. melitensis, B. abortus, and B. suis – and non-Brucellosis-Causing Brucella Species (NBBS), which encompass B. anthropi and B. intermedia originating from the former Ochrobactrum genus [17, 18]. While BBS species are zoonotic, requiring longer antimicrobial therapy due to their animal reservoir and potential for insidious, tissue-invasive infections, NBBS are typically opportunistic pathogens linked to healthcare environments.

“The most significant distinctive concern of B. anthropi and B. intermedia are the opportunistic nature and ability of NBBS to acquire and develop antimicrobial resistance,” researchers noted. However, they lack the potential for bioterrorism associated with the more traditional Brucella species.

Incidence and Risk Factors in Saudi Arabia

In Saudi Arabia, where brucellosis remains endemic [11, 19, 20], the study revealed a significantly lower incidence of B. anthropi and B. intermedia compared to brucellosis-causing species. Over an eight-year period at a large referral center, the average annual incidence was 2.05 per 100,000 blood cultures for the newly classified species, versus 39.05 per 100,000 for traditional brucellosis.

The majority of patients in the case series were elderly individuals with end-stage renal disease (ESRD) undergoing hemodialysis via central venous catheters (CVC). Additional risk factors included diabetes, malignancy, and recent surgical interventions – all conditions that compromise immune defenses and increase susceptibility to bacteremia [28, 29].

Diagnostic Difficulties and the Role of Advanced Testing

Symptoms and initial laboratory data across all cases were non-specific, often delaying definitive identification. The resemblance of these bacteria to other gram-negative organisms, coupled with limitations in commercial microbiologic diagnostics, contributes to the challenge [21]. Instances of misidentification are well-documented; for example, B. intermedium, B. pseudogrignonense, and B. tritici have been previously misidentified as B. anthropi [22, 23, 24, 25, 26]. Conversely, Brucella melitensis has been misidentified as B. anthropi [16, 21, 27].

Researchers emphasize the potential role of advanced diagnostic techniques. “MALDI-TOF mass spectrometry, DNA sequence analysis and 16S rDNA sequencing could guide the accurate identification,” they stated.

Antimicrobial Resistance and Treatment Considerations

B. anthropi isolates in the cohort demonstrated carbapenem non-susceptibility and high MICs to penicillin and cephalosporins, attributed to harboring OCH β-lactamase genes leading to AmpC-like resistance. However, they exhibited low MICs to ciprofloxacin, TMP/SMX, and carbapenem.

While treatment strategies for these emerging Brucella species are not yet well-defined, the approach appears similar to that for other resistant gram-negative bacteria. Carbapenems were the most commonly used therapy in the cohort, despite the availability of alternatives, with favorable outcomes. Further research is needed to assess the efficacy of ciprofloxacin and TMP/SMX as monotherapy.

Beyond Bacteremia: Diverse Infection Sites

While bacteremia was a common presentation, the literature reveals B. anthropi and B. intermedia can cause a diverse range of infections, including brain abscess [31], prostatitis [32], osteochondritis [33], osteomyelitis [34], ophthalmitis [35], and meningitis [36]. Interestingly, biliary growth of both pathogens was observed in the current cases, mirroring reports of isolation from the gastrointestinal tract [3, 22, 23, 24, 37, 38, 39]. This raises questions about potential gut translocation or lapses in infection control.

Pediatric cases in the cohort primarily presented with hospital-acquired pneumonia, contrasting with reports in the literature where bacteremia is more common in pediatric patients, particularly those with central lines [40, 41, 42, 43, 44].

The Importance of Vigilance and Enhanced Infection Control

The study underscores the importance of recognizing the distinction between these emerging Brucella species and their more concerning counterparts. Researchers suggest adding a clarifying comment to microbiology reports, particularly in endemic regions, to avoid confusion. Furthermore, differentiating between true bacteremia and contaminated cultures is crucial, aligning with principles of antibiotic stewardship.

Despite limitations including a small sample size and single-center data, this case series provides valuable insights into the clinical presentation and diagnostic challenges posed by B. anthropi and B. intermedia. It highlights the need for local epidemiological data, improved diagnostic accuracy, and enhanced infection prevention strategies to effectively address this emerging threat. .