Delayed but Salvaged: Rhodococcus Lung Abscess in a Patient With Undiagnosed HIV/AIDS

Introduction

Rhodococcus species is a recognized but rare human pathogen. It causes opportunistic infections in immunocompromised hosts, including individuals with HIV/AIDS, and predominantly causes pulmonary infections [1,2]. If undiagnosed and untreated, Rhodococcus infections can present as a multisystem, disseminated disease with high mortality [3]. We present a case of delayed diagnosis of HIV/AIDS due to poor awareness of the association of Rhodococcus infections with HIV/AIDS. To the best of our knowledge, only 3 cases of Rhodococcus infections have been reported from Pakistan, but none in the HIV population [4–6].

Case Report

INITIAL PRESENTATION:

A previously healthy non-smoking man in his late 30s presented to the pulmonology clinic with a 1-month history of intermittent high-grade fever, night sweats, weight loss of 10 kg, dry cough, and left pleuritic chest pain. He denied drug allergies, recent travel, or substance abuse. He was married, worked at the airport, and reported no exposure to animals or soil.

DIAGNOSTIC WORKUP:

Chest X-ray showed left hilar lymphadenopathy and ill-defined opacity in the left lower zone (Figure 1A). HIV testing and sputum acid-fast bacilli studies were ordered; they were neither performed nor followed up in the pulmonology clinic. Blood cultures were not done. Chest computed tomography (CT) showed a 55×41 mm cavitating soft tissue lesion in left lower lobe, left hilar lymphadenopathy, and few enlarged mediastinal lymph nodes (Figure 1B).

THERAPEUTIC COURSE:

The patient sought a second opinion from another tuberculosis (TB) treatment center. Approximately 5 weeks after symptom onset, he was started on empiric anti-tuberculous therapy with HREZ (isoniazid, rifampicin, ethambutol, pyrazinamide), oral clindamycin 300 mg 3 times daily, and ceftriaxone 1 g IV twice daily for suspected pulmonary TB and lung abscess, respectively. Dexamethasone was given for a week for an unclear indication. An ultrasound-guided lung biopsy was planned but not performed, due to poor follow up and lack of care coordination.

Three weeks after anti-tuberculous therapy initiation, oral levofloxacin was added for persistent symptoms. Seven weeks after therapy initiation, a follow-up chest CT showed worsened left lower lobe cavitation measuring 60×49 mm (Figure 1C). Subsequently, the CT-guided lung biopsy procedure was re-initiated, contingent upon confirming patient adherence. Ten milliliters of frank pus was aspirated. While cultures results were pending, clindamycin and ceftriaxone were re-prescribed, and voriconazole 200 mg twice daily was added empirically. Gram staining showed numerous pus cells and few gram-positive rods, initially identified as Corynebacterium spp. Final growth isolated Rhodococcus spp.; however, speciation could not be done, as shown in Table 1, which details the antimicrobial susceptibility testing of Rhodococcus spp.

Anaerobic, fungal, and mycobacterial cultures were negative. Histopathology showed moderate interstitial inflammation and focal fibrin. Results were negative for malignancy or granuloma. Clindamycin and voriconazole were stopped. Anti-tuberculous therapy was discontinued after 9 weeks. The administration of parenteral linezolid was added to the ceftriaxone.

The infectious disease department was consulted more than a month after Rhodococcus lung abscess was diagnosed. At this point, the patient’s symptoms were ongoing for 5 months. An urgent HIV test showed positive results. His baseline CD4 count was 162 cells/mm³, and HIV viral load was 533 552 copies/mL. Due to the unavailability of anti-retrovirals in the private sector in Pakistan, he was referred to the provincial AIDS control program. Antiretroviral therapy (ART) was initiated with tenofovir disoproxil fumarate 300 mg once daily, lamivudine 300 mg once daily, and dolutegravir 50 mg once daily. Prophylaxis was initiated for Pneumocystis jiroveci, with daily trimethoprim-sulfamethoxazole, and Mycobacterium avium complex with weekly azithromycin. Antibiotics were adjusted to moxifloxacin and linezolid. Rifampin could not be started, due to unavailability. Ceftriaxone was discontinued.

The patient’s course was complicated by polymicrobial gram-negative pneumonia approximately 5 to 6 weeks after ART initiation. He developed a new-onset cough, fever, and hemoptysis. Repeat CT of the chest revealed 87×80 mm left lower lobe cavitary consolidation, surrounding centrilobular nodules, mild left-sided pleural effusion and multiple enlarged left hilar lymph nodes (Figure 1D). Bronchoalveolar lavage identified Klebsiella species and Pseudomonas aeruginosa (Tables 2, 3). Fungal and acid-fast bacilli cultures were negative. The cytology report showed acute inflammation with macrophages and columnar cells admixed with mucus. Culture-directed therapy with ertapenem for 1 week was prescribed for Klebsiella. For P. aeruginosa, ciprofloxacin was started. Unfortunately, the patient developed shivering, rigors, and fever after the first dose of ciprofloxacin, leading to discontinuation. Moxifloxacin was held off initially then resumed with no intolerance (Figure 2).

FOLLOW-UP:

As of this writing, the patient is taking a 7-month course of oral moxifloxacin and linezolid. A follow-up CT of the chest showed marked interval resolution (Figure 3). He has returned to work and has adhered to ART, with a CD4 count of 221 cells/mm3 and viral load of 187 copies/mL.

Discussion

Rhodococcus spp. is a gram-positive, facultative, coccobacillary organism commonly found in soil and water. It is an established pathogen in veterinary medicine [1,2]. Rhodococcus infections are increasingly reported in immunocompromised hosts, such as individuals with HIV/AIDS, organ transplant recipients, and patients on immunosuppressive therapy or long-term steroid use [7–12]. A small number of cases has also been reported in immunocompetent hosts. The main mode of transmission is through inhalation of contaminated aerosols and dust, while secondary intestinal infections can result due to the aspiration of tracheal secretions, or via direct exposure to wounds or mucous membranes [3].

There is paucity of literature on Rhodococcus infections from Pakistan. Three non-HIV cases are reported from Karachi City (Table 4) [4–6]. All 3 patients reported environmental and animal exposure, which is in contrast to our case. Two of the 3 patients had undergone renal transplant and developed pneumonia and parietal lobe brain abscess, respectively [5,6]. The third immunocompetent patient presented with an extremely rare presentation of recurrent pericardial effusion and anterior mediastinal mass [4]. One of the 2 renal transplant patients with pneumonia died [5]. To the best of our knowledge, this is the first reported case of Rhodococcus lung abscess in an AIDS patient from Pakistan.

Our case provides a real-world example that underscores the numerous obstacles clinicians must overcome in diagnosis and management, which are chiefly attributable to the country’s poor healthcare infrastructure. These challenges are highly intricate and interlinked. Diagnostically, HIV screening and image-guided lung biopsy were delayed. Acid-fast bacilli studies were also not done.

Retrospective analysis suggested the issue stemmed largely from a lack of continuous care, a problem intensified by several factors: poor communication between the 2 treatment centers, the patient seeking care elsewhere, and the failure to maintain coordinated records, despite the involvement of a teaching hospital. After the Rhodococcus lung abscess was diagnosed, HIV screening was still not addressed until referral to the infectious disease department. Pakistan ranks fifth among countries with the highest TB incidence globally [13]. Despite World Health Organization guidelines, HIV screening is not routinely done in suspected and/or confirmed TB cases [12,14], let alone upon the rare diagnosis of Rhodococcus lung abscess, for which the providers’ expertise was limited. Preliminary reporting identified Rhodococcus spp. as Corynebacterium spp.; hence, it was deemed as contamination [1,6,15]. Identification to species level could not be done, due to non-availability of the isolate when the case was discussed with the microbiologist. Pakistan is also the third-highest antibiotic-consuming country among low- and middle-income countries, with over-the-counter access to antibiotics without a prescription [16]. Our patient was given empiric antibiotics, antifungals, and steroids, with no meaningful response. Empiric anti-tuberculous treatment for clinical suspicion of pulmonary TB was then added. This is a common clinical practice in Pakistan and other settings with high TB burden [7,11,12]. There was no animal exposure to augment the above [1,2]. The absence of an antimicrobial stewardship program was clearly reflected in the treatment prescribed. The patient was kept on parenteral antibiotics, including linezolid, which has 100% oral bioavailability. Despite significant TB prevalence, rifampicin was not available as an individual pill, which precluded its use. Lastly, ART is supervised under the provincial AIDS control program. These programs lack the multi-disciplinary support needed to manage co-infections in patients with AIDS. This is a major barrier in the care of HIV/AIDS with rare and serious co-infections. To overcome the above challenges, it was necessary that the patient received ART and Rhodococcus treatment at separate locations.

The clinical manifestations of Rhodococcus infection are varied, presenting with constitutional symptoms, cough, fever, chest pain, and weight loss. The most common presentation is pulmonary infection in approximately 80% of cases, presenting with cavitary pneumonia, lung abscess, and pyothorax. Reported extra pulmonary infections include bacteremia; bone and joint infections; pericarditis or endocarditis; pericardial effusion; traumatic keratitis; endophthalmitis; abscesses of the brain, prostate, spleen, renal, liver, thyroid, or retroperitoneum; peritonitis; mesenteric and cervical adenitis; ventricular shunt infection; subcutaneous and deep tissue infections; and otomastoiditis [1,4,10,15,17]. Differential diagnoses include TB, non-tuberculous mycobacteria, nocardiosis, actinomycosis, or fungi [5,7,15,18].

Rhodococcus infections in patients with HIV have higher reported mortality (34.24%) than that in immunocompetent patients (10.87%) or non-HIV related immunosuppression (approximately 20–25%), mainly due to immunodeficiency and delayed recognition and treatment of underlying Rhodococcus infection [1–3,15,17].

Treatment includes combination antibiotics with at least 2 agents in immunocompromised hosts. For initial therapy, a macrolide or fluoroquinolone in combination with rifampin or with 2 of the following is recommended: vancomycin, imipenem, linezolid, or an aminoglycoside. It is preferred to use antibiotics with intracellular activity, such as rifampin, fluoroquinolones, and azithromycin, because survival within histiocytes is a significant virulence determinant in Rhodococcus equi pathogenesis [5,15,17]. In our patient, initial treatment consisted of ceftriaxone and linezolid, as culture-directed treatment. Due to the unavailability of rifampicin, the regimen was later modified to moxifloxacin to enhance intracellular drug activity in combination with linezolid. In immunocompetent patients, single-agent treatment with macrolide or fluoroquinolone is usually sufficient [2,15].

Conclusions

There is an acute need for a robust healthcare delivery system in Pakistan, a major contributor to global TB burden and the third-highest antimicrobial consuming country among low- and middle-income countries. Rhodococcus infection should alert physicians for prompt HIV screening. Attempts should be made for complete identification and antimicrobial susceptibility testing in discussion with the microbiologist, whenever possible. Empiric combination therapy should be adjusted to in vitro susceptible combination therapy. Timely diagnosis of HIV is crucial for early ART initiation to optimize patient outcomes. An infectious disease consultation is strongly encouraged.