Case of the Month

Case presentation

Baby  

• Date Of Birth- 08/01/2022 

• Gestational age 32 weeks 

• Birthweight: 1380g female, inborn 

• NVD 

Mother: 

• 18-year-old; G2P1 

• WR negative, Rh positive. 

 • HIV positive, viral load - 4280 and CD4- 135 

 • CD4 135 

• Has been on HAART since 2007 Regimen 

• Premature rupture of membranes (PROM) at 32 weeks

08/01/2022 Post-delivery baby was admitted to the neonatal unit with respiratory distress syndrome (RDS), requiring respiratory support with nasal continuous positive airway pressure (nCPAP). Commenced on Azidothymidine (AZT) and Nevirapine for HIV prophylaxis. HIV Polymerase Chain Reaction (PCR) done at birth was negative. Also commenced on Ampicillin and Gentamicin. She weaned successfully to nasal cannula oxygen at 2l/min. 

12/01/2022 (day 5 postnatal age) the baby had an increased work of breathing and was placed back on nCPAP. A diagnosis of a healthcare associated infection was considered. Sepsis work-up revealed: CRP<1, and blood culture - negative. Antibiotics started at this time were Piperacillin/tazobactam and Amikacin. Cranial ultrasound was normal 

Baby developed hyperglycaemia (a random glucose – 22.8mmol/l) which was persistent despite reducing the glucose delivery and requiring insulin infusion. Work up for persistent hyperglycaemia revealed: 

Cortisol – 245 nmol/l (morning – 133-537nmol/l, evening 68-327nmol/l) 

Insulin 1.2 IU/L (2.6-24.9) 

C-peptide 1.0 ug/L (1.1-.4.4) 

Antibodies to glutamic acid decarboxylase (Anti-GAD antibody) - negative; Insulin Ab; HBA1C - rejected 

The differential diagnosis included transient diabetes mellitus vs. neonatal diabetes mellitus. A genetics consult was requested to assess causes for neonatal diabetes. 

19/01/2022 (day 12 postnatal age) – the neonate was noted to be hypertensive 94/52 MAP 66 mmHg. MAP according to GA 34 -67mmHg. HR 149 and HGT – 16.6. Weaned to NPO2 

20/01/2022 (day 13 postnatal age) Sepsis work up done. Klebsiella pneumoniae ESBL cultured in blood. Full blood count showed: WCC 1.2 X109/l, Hb 7.8 g/dl, platelets 153 X 1012/l, neutrophils 0.30 and lymphocytes 0.80; CRP was 90 mg/L. Initially placed on Piperacillin/tazobactam and Amikacin which was then changed to Meropenem once the organism and sensitivities were known. Another concern was whether the HGT was due to sepsis. The HGT decreased to 9.1mmol/l and the insulin infusion was stopped. An abdominal sonar was requested to check the pancreas. At the time of this sepsis the HGT increased again to 18.7 mmol/l and the insulin infusion was prescribed again. On treatment the baby’s HGT decreased, and the insulin was stopped again on the 26/01/2022. The platelets also decreased to 26 X 109 /l. 

21/01/2021 A repeat blood culture result was Candida albicans and Fluconazole was added to the Meropenem. 28/01/2022 Hyperglycaemia was reported again, and the insulin infusion was re-commenced. HGTS dropped to 14.8 mmol/l and insulin was weaned and then stopped. 

29/01/2022 Another repeat culture was drawn on day 10 of Meropenem treatment, which subsequently grew a Klebsiella pneumoniae ESBL and Meropenem was continued. 

29/01/2022 Baby presented with abdominal distension and a tachycardia. The concern was a new sepsis with NEC or a septic ileus and a possible abdominal collection of fluid. Colistin was added to the Meropenem after another blood culture was drawn. The baby had haemetochezia and Pantoloc was commenced. HGT was 18mmol/l. The baby was kept nil by mouth. 

31/01/2022Abdominal sonar reported no abnormalities. Colistin was stopped after 5 days. 

03/02/2022 – the baby had an increased work of breathing and hypotension and was recommenced on nCPAP and an inotrope. The HGT was 31mmol/l. The baby had liver dysfunction and jaundice. The LFT had a conjugated hyperbilirubinaemia picture. In view of the multiple positive cultures of Klebsiella pneumoniae an ECHO and a cranial ultrasound (CUS) was requested to check for vegetations. The ECHO reported a PDA and no vegetations. The CUS was normal. A BDG > 500 and had been on Amphotericin B. 

 11/02/2022 the baby was intubated as she was not coping on nCPAP. 

06/02/2022 the baby had an FBC that revealed a pancytopaenia: WCC 2.31X109/L; Hb 5.2g/dl and platelets of 3 X 10 9/l. Blood culture positive for a Klebsiella pneumoniae ESBL. A primary immunodeficiency workup was drawn. A Cytomegalo virus viral load (CMV VL) was normal. 

12/02/2022 Results of the immunodeficiency workup. – WCC 3.40 X 109/l, lymphocytes 12.90, absolute lymphocytes 0.44 (low), Total T cells (CD3) 325 (low), Helper T cells CD4 246 (low), cytotoxic T cells CD8 74 (low), CD 19 39 (low), Natural Killer cells 54 (low), IgG 4.39 (high), IgA < 0.5 (low/high), IgM 2.35 (low/high). 

18/02/2022 the neonate developed multiple scalp abscesses. These were drained and a pus swab was sent off which cultured Klebsiella pneumoniae. A repeat abdominal ultrasound on the 11/02/2022 – subhepatic abscess at 2.4mm, 18/02/200 1.5 mm and on the 23/02/2022 – no collection viewed, resolved. 

24/02/2022 A barium enema result was normal. On the 28/02/200 the CRP was 5 IU/L. The baby is still on Meropenem. Repeat blood culture on the 18/02/2022 was negative. The decision was to complete antibiotics after 14 days negative culture or 6 weeks of treatment.

Management

The patient was treated with Meropenem for 6 weeks and we looked for source control. The neonate had an abdominal sonar and echocardiogram and a cranial sonar. A bone scan was not done. The neonatal diabetes was treated with insulin infusions no long-term management was prescribed as the neonate improved. A genetics consult was requested to investigate for genetic causes of the neonatal diabetes. In view of the persistent positive cultures the neonate was investigated for a primary immunodeficiency. The patient was cohorted for the persistent infection and transmission-based precautions were instituted.

Discussion

Definition: Primary immune deficiency diseases (PIDDs) are rare, genetic disorders that impair the immune system. Without a functional immune response, people with PIDDs may be subject to chronic, debilitating infections, such as Epstein-Barr virus (EBV), which can increase the risk of developing cancer. Some PIDDs can be fatal. Many elements of the human immune system in healthy newborns are distinct since it is planned to make the evolution possible from intrauterine to exterior world. Many types of primary immunodeficiency diseases (PIDs) appear in the neonatal period, but recognizing and managing PIDs in the newborns are challenging Epidemiology (burden and local relevance): PIDD results from genetic mutations affecting one or several components of the immune system, including cells and proteins. These mutations may cause parts of the immune system to be present in lesser quantities than normal. The normal neonate’s immune system is anatomically completed but antigenically inexperienced and shows somewhat decreased role of several immunological pathways. Aside from anatomic characteristics (e.g., thin skin and mucosal barriers) of newborn, weakened proinflammatory and T-helper cell type 1 cytokine release and lessened cell-mediated immunity predispose the neonate more susceptible to all types of infections. Preterm newborn additionally demonstrates fragile skin, moderate-to-severe hypogammaglobulinemia, lower lymphocyte counts, plasma complement, and antimicrobial peptide levels Clinical features: One of the most common signs of primary immunodeficiency is having infections that are more frequent, longer lasting, or harder to treat than are the infections of someone with a typical immune system. You may also get infections that a person with a healthy immune system likely wouldn't get (opportunistic infections). Signs and symptoms differ depending on the type of primary immunodeficiency disorder, and they vary from person to person.

Signs and symptoms of primary immunodeficiency can include: 

• Frequent and recurrent pneumonia, bronchitis, sinus infections, ear infections, meningitis, or skin infections 

• Inflammation and infection of internal organs 

• Blood disorders, such as low platelet count or anaemia 

• Digestive problems, such as cramping, loss of appetite, nausea, and diarrhoea 

• Delayed growth and development 

• Autoimmune disorders, such as lupus, rheumatoid arthritis, or type 1 diabetes 

Standard diagnostic: The most prognostic factor for a PID is a family history of immunodeficiency, confirmed or suspected – here the mother was HIV positive. There are more than 300 types of primary immunodeficiency disorders, and researchers continue to identify more. They can be broadly classified into six groups based on the part of the immune system that's affected: 

• B cell (antibody) deficiencies 

• T cell deficiencies 

• Combination B and T cell deficiencies 

• Defective phagocytes 

• Complement deficiencies 

• Unknown (idiopathic)

What IPC measures are to be instituted once a patient has cultured an ESBL organism? 

Standard precautions – emphasis on hand hygiene and the WHO 5 moments 

Transmission based precautions 

Contact precautions Used to prevent and control infections that spread via direct contact with the patient or indirectly from the patient’s immediate care environment (including care equipment). This is the most common route of cross-infection transmission. 

Cohorting of patients 

PPE - Plastic aprons and disposable gloves should be worn when in direct contact with the patient or the patient’s immediate environment 

Hand hygiene - Hands must be decontaminated as per your 5 moments for Hand Hygiene: 1. Before touching a patient 2. Before clean/aseptic procedure 3. After body fluid exposure risk 4. After touching a patient 5. After touching patient surroundings 

Patient Care Equipment -Where available, use single use patient care equipment. All single use patient care equipment must be discarded as clinical waste. Equipment should be kept to a minimum. All shared or reusable equipment must be decontaminated between patients using a chlorine releasing agent at a dilution of 1,000 parts per million available chlorine (ppm available chlorine). Please refer to manufacturers’ instructions for compatibility of product. Communal facilities such as baths, bidets and showers should be cleaned and/or decontaminated between all patients

Environmental cleaning - Enhanced routine daily cleaning of the patient’s room with a chlorine releasing agent at a dilution of 1,000 parts per million available chlorine (ppm available chlorine), should be undertaken by cleaning staff until instructed otherwise. It is the responsibility of nursing staff to ensure that cleaning staff are aware of this requirement Following the discharge/transfer/death of the patient, the room should have a terminal clean carried out prior to the next patient being admitted 

Clinical Waste -All waste must be discarded as healthcare risk waste. 

Linen - All linen should be laundered as infectious i.e., placed into a colour coded plastic bag for infectious linen (according to hospital protocol). Labels should be attached to each linen bag on sealing, clearly stating: - Hospital of origin - Ward or Department - Date 

Safe management of blood and body fluid spillages - Remove spillage immediately with disposable paper towel, then clean with normal detergent prior to applying a chlorine releasing agent to reduce the risk of chemical reaction. Spillages must be decontaminated with a chlorine releasing agent using the following dilutions: Blood spillages (or bodily fluid with associated blood): a dilution of 10,000 parts per million available chlorine (ppm available chlorine. Body fluid spillages (with no associated blood): a dilution of 1,000 parts per million available chlorine (ppm available chlorine).