Streptomyces infection in Cushing syndrome: A case report and literature review.

Streptomyces are saprophytic soil organisms rarely known to cause invasive infections. Streptomyces is the largest genus, producing antibacterial, antifungal and antiparasitic drugs. The case was a 24-year-old man, admitted for sudden dyspnea, fever and sputum and decreased sound in the left lung. The chest X-ray showed hydropneumothorax. After chest tube insertion, lung expansion did not happen. Pleural effusion was exudative with gram-positive bacillus and Streptomyces in culture. Owing to symptoms of Cushing in history, examination and laboratory work-up for Cushing was done and finally he underwent bilateral adrenalectomy. The patient was on antibiotic broad spectrum antibiotic and then was changed to antibiotic as organism was sensitive to and discharged with clarithromycin for 6 months. Streptomyces happens in immunodeficient patient. Diagnosis is based on culture and contamination was ruled out. Treatment period is longer for patients owing to slow growing nature.

INTRODUCTION

Streptomyces are saprophytic soil organisms is rarely known to cause invasive infections other than mycetoma.[1] Streptomyces species are most widely known for their production of antibiotics as secondary metabolites.[2]

The genus Streptomyces contains more than 500 species. Streptomyces is known as saprophytic soil organisms that lead to non-invasive infection other than in an immunodeficient condition that cause invasive infection. Streptomyces species are most popular for antimicrobial drug production. Streptomyces is the largest antibiotic-producing genus, producing antibacterial, antifungal and antiparasitic drugs and also a wide range of other bioactive compounds, like immunosuppressants.[3] The pulmonary symptoms are pneumonia and may lead to nodular or abscess formation.

CASE REPORT

Patient was a 24-year-old man, admitted to hospital due to sudden dyspnea for 3 days with cough and yellowish sputum from almost 7 days before admission. He had fever for 5 days before admission. He was healthy until 50 days before admission and was sent to the tropical city for military service where he had an insect bite. After the bite, swelling and edema of upper limb occurred followed by edema on the face and body, acne and weakness of proximal muscles 2 days later. During 1 week, body edema decreased while muscle weakness, acne and facial edema remained. Acnes spread to the anterior chest and face.

On physical examination: He was ill and had a moon face appearance; a lot of papulopustular rashes were seen in the face and anterior of the chest. He was febrile with 39.3°C oral temperatures, respiratory rate: 30/min and pulse rate 115/min, blood pressure 145/95 mmHg. O2 saturation was 86%, White blood cells: 20500/cm, polymorphonuclear leukocyte: 90%, erythrocyte sedimentation rate: 72 mm at 1 h, k: 2.8 mEq/l, pH: 7.52 and he had a decreased sound in left lung with hyper resonance in upper and dullness in the lower portion of the chest, the force of proximal muscle was 3/5. Chest X-ray showed hydropneumothorax [Figure 1].

Figure 1

Chest X-ray showed hydropneumothorax

Chest computed tomography scans showed pneumothorax, plural effusion in the left side accompanied by lung collapse. Also, there were several lung consolidations with pleural thickening [Figure 2].

Figure 2

Chest computed tomography scans showed pneumothorax

Plural effusion, lung consolidations with pleural thickening

Thoracentesis was done and analysis for protein, lactate dehydrogenase, glucose, PH, cytology, culture and smear was sent. Blood culture was asked because of systemic inflammatory response syndrome.

Pleural fluid was indicative of empyema with glucose 30 mg/dl and pH: 7, so chest tube was inserted and a broad spectrum was administered until smear and culture of pleural fluid being ready. After chest tube insertion, chest X-ray was taken which showed decreased pleural effusion, but lung expansion did not occur. Bronchoscopy was normal. Thoracoscopy was done for decortication of pleural thickening [Figures 3 and 4].

Figure 3

Computed tomography scan shows pleural thickening

Figure 4

chest X-ray shows persistent pneumothorax after chest tube insertion

Pleural biopsy showed fibrin deposition and chronic inflammatory cell infiltration, with chronic inflammation [Figure 5].

Figure 5

fibrin deposition and chronic inflammatory cell infiltration, with chronic inflammation

A smear of pleural fluid showed gram positive beaded basil and aerobic culture of pleural fluid confirmed Streptomyces with filamentous appearance. Pleural biopsy culture justified Streptomyces too. Culture was negative for acid fast bacilli. Bacteriogram reveal sensitivity to co-trimoxazole, meropenem, ciprofloxacin, cefotaxim, tetracycline and claritromycin and resistance to ampicillin, ceftazidim, cefotaxim and piperacillin-tazobactam. Blood culture was negative for specific organisms.

During hospitalization polyuria occurred. In work-up, hypokalemia and hyperglycemia happened. Because of symptom, physical examination and laboratory test, a work-up for Cushing was done.

Urinary free cortisol was 600 μg/24 h, over-night dexametason suppression test was positive justified Cushing syndrome. Adrenocorticotropic hormone (ACTH) was 180 μg/dl that showed ACTH dependent Cushing syndrome. High-dose dexametason suppression test was done and the suppression of cortisol did not occur, brain magnetic resonance imaging (MRI) did not show adenoma. Rapid progression of symptom and normal brain MRI confirm ectopic ACTH, but no origin was found in the work-up.

Bilateral adrenalectomy was done and histopathology confirmed adrenal hyperplasia without malignancy [Figure 6].

Figure 6

Adrenal hyperplasia without malignancy

Empirical treatment was converted to meropenem for 6 weeks. He was recommended to use claritromycin for 6 months at the time of discharge.

DISCUSSION

Streptomyces is known as soil organisms with highly opportunistic nature of the infections. Streptomyces species are gram-positive filamentous bacteria and soil residents.[1] Most clinical microbiology laboratories suggest a likely Streptomyces species identification i.e., long filamentous gram-positive bacteria that grow aerobically and are negative for partially acid-fast stain.[2]

Some antibiotics used for treatment of bacterial, mycobacterial, fungal and parasitic infections are produced by Streptomyces genus and among them the most important drugs are: Chloramphenicol, daptomycin, fosfomycin, lincomycin, neomycin, puromycin, streptomycin, tetracycline and clavulanic acid.[3] Over a period of time these organisms were known as fungi as they true hyphae, but they are now recognized as bacteria. Streptomyces and Nocardia species are aerobic actinomycetes.

For stretomyces infection a pre-existing condition such as cancer, acquired immunodeficiency syndrome or human immunodeficiency virus infection, the presence of a central venous catheter and prosthetic heart valve, exogenous glucocorticoid are required.[2] Although, Kofteridis et al. reported pulmonanary Streptomyces infection in immunocompromised patients. The most common presentation of Streptomyces infection is mycetoma, which is a chronic suppurative infection of the skin and underlying soft-tissue. Visceral infections with these organisms appear to be rare.[4]

Until recently, pneumonia and other symptomatic infections due to Streptomyces were considered to be rare and limited to the immunocompromised condition.[56] There have been only a few reports of Streptomyces species causing infection other than mycetoma. Pneumonia is a rare clinical feature of Streptomyces infection as only 8 cases have been reported during the last 59 years.[5] Kohn et al. reported a septicemia and primary lung involvement due to Streptomyces infection. Caron et al. described a nodular infiltration of the lung in human immunodeficiency virus (HIV) infected patient and Ahmed et al. presented a case of Streptomyces pneumonia and monoartritis in an advanced HIV infection and a case of sarcoidosis with Streptomyces infection is reported during November 2012.[178]

Microbiological and pathological correlations are required to differentiate Streptomyces infection from contamination. Kapadia et al. showed that diagnosis of Streptomyces is difficult and clinical and laboratory combination is needed and clinical manifestations, isolation of the organism from sterile sources, direct microscopic identification of infected tissue and exclusion of other causes must be paid attention. By using combinations of at least 2 of these criteria, they could diagnosis true infection.[2] Contamination shows usually a single colony from isolator culture. Biotechnology science has led to the development in Streptomyces identification through 16s ribonucleic acid gen sequencing, but still is not available in most countries.[5]

Differential diagnosis of Streptomyces is anaerobic actinomycetes and aerobic Nocardia and Rhodococcus that are usually partially acid-fast.[2]

Kapadia et al. showed that Streptomyces organisms were consistently susceptible to amikacin; frequently susceptible to imipenem, clarithromycin or erythromycin, minocycline and trimethoprim sulfamethoxazole; and infrequently susceptible to ciprofloxacin and ampicillin.[2] Burman et al. reported a successful treatment with clarithromycin for 6 months that lead to recovery of pulmonary infection.[4]

Kofteridis et al. has reported that the most potent drug was minocycline, imipenem, erythromycin, doxycycline and aminoglycoside, whereas significant percentage were resistant to trimethoprim-sulfamethoxazole, ampicillin and ciprofloxacin and hence they treat their patient with doxycycline for 6 months. Streptomyces is a slow growing bacteria, so the duration required is a long period of time. In the literature it has been mentioned as 6-24 weeks of duration.[5]

Riviere et al. in pulmonary Streptomyces infection in patient with sarcoidosis, suggested treatment with intravenous imipenem (2 g/day for 14 days) and amikacin (1 g/day for 3 days), after antimicrobial susceptibility tests, the treatment was changed to oral rifampin (1.2 g/day) and ciprofloxacin (1.5 g/day) for 6 months.[1]

CONCLUSION

Streptomyces infections are rare and occurred mainly in immunodeficient condition caused by cancer, chemotherapy and other immunosupreesd condition. It is important to differentiate true infection from contamination. If Streptomyces infection occurred in patients, attention to any condition affected immunity must be done. Its treatment is longer than other typical infection due to slow growing nature.