Grand Rounds

Polymicrobial infection in immunocompromised host - How to manage?

1Department of Pediatric Infectious Diseases, B J Wadia Hospital for Children, Mumbai, Maharashtra, India, 2Grant Government Medical College, Sir JJ Group of Hospitals, Mumbai, India, 3Consultant in Pediatric Infectious Diseases, Levioza Health Care, Mumbai, India

Address for Correspondence: Suhani Jain, Flat number 402, Ramdeo Arise, Behind Hotel Airport Centre Pt, Wardha Road, Nagpur-440025.

Keywords: Immunocompromised infants, STAT1 mutation, Polymicrobial infection

Clinical Problem :
A 2 year 9 month old male suffering from STAT1 gain of function mutation on whole exome sequencing diagnosed at the age of 6 months in view of recurrent pneumonia presented to us with fever and cough for 15 days. There was no exposure to a patient with tuberculosis. The child was on baricitinib for past 2 years. He was also on Fluconazole prophylaxis for initial 6 months and then oral Voriconazole for 6 months for fungal prophylaxis but was off antifungal for the past 6 months. On presentation, the child weighed 9.6 kg [weight for age <3rd centile as per Indian Academy of Pediatrics (IAP) growth chart], height was 88 cm (length for age 3rd to 50th centile as per IAP growth chart), heart rate was 130/min, respiratory rate was 42/min with mild respiratory distress and subcostal retractions. Oxygen saturation was 88 % on room air. Other general examination was normal. On respiratory system examination, there were bilateral crepts in mammary and axillary regions on auscultation. Other systemic examination was normal. Child was started on supportive treatment with intravenous fluids, oxygen by nasal prongs, broad spectrum antibiotics (injectable Meropenem at 20 mg/kg/dose 8 hourly and Vancomycin at 15 mg/kg/dose 8 hourly) with antifungal (Injectable Fluconazole at 12 mg/kg/dose once a day) and baricitinib was stopped. Investigations are depicted in Table 1. Chest X-ray had right lower zone inhomogenous opacification with cavity with infiltrates in bilateral lungs as shown in Figure 1. HRCT chest showed necrotising pneumonia with large irregular air filled cavitatory lesion and multiple necrotic foci in the right lower lobe along, similar area of consolidation and necrosis in the right middle lobe, nodular infiltrates in both lungs with subsegmental areas of consolidation in the left lower lobe. Gastric lavage (GL) Xpert Mtb/Rif assay detected mycobacterium tuberculosis with no Rifampicin resistance. Antituberculous therapy (ATT) consisting of Isoniazid (H) (8 mg/kg/day), Rifampicin (R) (20 mg/kg/day), Pyrazinamide (Z) (35 mg/kg/day), Ethambutol (E) (25 mg/kg/day) was started. Bronchoalveolar lavage (BAL) fungal culture grew Candida tropicalis resistant to Fluconazole and Voriconazole and sensitive to amphotericin B, Caspofungin and micafungin. Hence Liposomal Amphotericin B was started at 3 mg/kg/day and Fluconazole was stopped. Blood culture did not grow any organism. Ultrasound abdomen was normal. BAL and whole blood cytomegalovirus (CMV) PCR was positive hence oral Valganciclovir (520 mg/sqm/day) was added. BAL multiplex PCR showed adenovirus for which the child was given Intravenous Immunoglobulin (IVIG) at dose of 400 mg/kg. Child became afebrile for 48 hours, but again started developing new onset fever spikes with aggravation of cough. Throat swab showed presence of influenza A and H3N2 on PCR for which Oseltamivir (3mg/kg/dose 12 hourly for 10 days) was added. Child became afebrile after 72 hours and oxygen saturation was maintained on room air. Blood CMV PCR was negative after 2 weeks of therapy. After 14 days of Inj amphotericin B, Posaconazole was added at dose of 6 mg/kg/dose 8 hourly. Child was shifted to Rifampicin devoid regimen of ATT and Ofloxacin was added and HZE was continued. Amphotericin B was stopped after 21 days and Posaconazole trough levels were sent. Posaconazole trough levels were <0.1, hence dose was increased by 25% and advised to repeat trough levels after 1 week. Repeat Chest Xray after 3 weeks showed some improvement as shown in Figure 2. He was discharged after 40 days of hospitalization on H, Z, E, ofloxacin, valganciclovir, posaconazole, pyridoxine.

Figure 1. Chest X-ray showing lower zone inhomogenous opacification with cavity with infiltrates in bilateral lungs.

Figure 2. repeat CXR after 1 month showing improvement.

Table 1. Serial laboratory parameters of the patient.
Laboratory parameter Day of presentation Day 5 Day 9 Day 11 Day 16 Day 18 Day 21
Hemoglobin (g/dL) 9.9            
Total leucocyte count (cells/cumm) 11,480
Absolute neutrophil count (cells/cumm) 9115
Absolute lymphocyte count (per 1572
Platelet count (cells/cumm) 3,06,000
C-reactive protein (g/L) 166 87     5    
Blood culture Negative     Negative      
Xpert Mtb/Rif (Gastric lavage) M.tb detected very low, rif resistance not detected            
BAL Multiplex PCR     Adenovirus detected        
Whole blood CMV Quantitative PCR     8564 copies/ml
Log10 value 3.93
      Below limit of detection
BAL Quantitative CMV PCR     103695 copies/ml
Log10 value 5.01
BAL gram stain     Few pus cells        
BAL KOH mount     Negative        
BAL bacterial culture     Streptococcus sanguinis        
BAL fungal culture     Candida tropicalis (colony count of <103 cfu/ml)        
Throat swab for influenza           Influenza A: detected
H3N2: detected
H1N1: not detected
Influenza B: not detected

How should patients with polymicrobial infections in immunocompromised patients be treated?
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