Clinical case study

V.

RAMASUBRAMANIAN: Hi, everybody. This is Dr. Ramasubramanian. I’m a consultant infectious diseases at Apollo Hospitals in Chennai, India. We are going through difficult times now. And the waves of pandemic are still washing over us. And unfortunately, antimicrobial resistance is still a major concern. During times of COVID, we have special challenges in managing the antimicrobial resistance issue. Because patients who come in with what appears to be a severe acute respiratory illness, it is difficult to categorically say this is COVID. Because it may be a community-acquired pneumonia.

There may be raised white cell count in patients who have been given steroids before they come to the hospital, especially if they have hypoxia, which may make it difficult to decide whether it’s a bacterial infection or whether it is a steroid response. The C-reactive protein, which is a marker of inflammation, may be elevated in COVID, making diagnosis– or shall I say, differentiating viral and bacterial infections– difficult. The process of investigating a COVID patient may also be challenging. Because there may be worries related to performing interventions like bronchoscopy, which may increase the transmission of the disease. And lastly, the response to treatment may also be difficult to monitor. Because COVID, per se, can behave in ways which are difficult to predict.

So we– it is very important that we have a regional recommendation or a policy which is hospital-specific or region-specific, so that we can approach management of patients, especially with regard to antimicrobial usage, in a better fashion. I’m going to illustrate the importance of having a local policy, and also the importance of using diagnostics in managing a patient with COVID so that we use antibiotics judiciously. This patient was a 57-year-old lady, who presented to us sometime during the May of 2021 during the peak of COVID season in India, especially in my state. She was a diabetic, a hypertensive, and also have had coronary artery disease.

She had a history of tuberculosis two years earlier, for which she had taken anti-TB treatment only for four months and had discontinued, but subsequently remained well. She presented to us with a six-day history of symptoms, progressive breathlessness. And when she came in, she was already requiring about six litres of oxygen. So she was resuscitated. A COVID test was sent, which came in positive. And she was started on dexamethasone, low-molecular-weight heparin. And she stabilised in the initial period. But subsequently, after a day or so in hospital, in spite of steroids, she continued to deteriorate and had to be ventilated. She was given tocilizumab because she was severely hypoxic. And fortunately, she responded.

And in a matter of a few days, she stabilised. And we were able to slowly wean her down. She continued to be on the ventilator. And she also had a central line, which was put initially by day 10 into the hospital stay in the ICU. She developed a high grade fever. There were no increased infiltrates on the chest X-ray. The respiratory secretions weren’t increased. So we considered the possibility of a central line-related infection because she had a central line in place for up to 10 days. So she was started on injection polymyxin, which is the usual choice of treatment in our centre.

I would add here that when she came in, because her procalcitonin was normal, she was not given any antibiotics for any bacterial infection. And the treatment was purely directed for only COVID. So when she developed a fever on day 10, she had not been exposed to any antibiotics. But as is the norm in my unit, anybody spending more than a week in the ICU who develops a hospital-acquired or a suspected hospital-acquired infection, we start them on polymyxin. Because that is the antibiotic which will work for bugs which are hospital-acquired. So with the suspicion of a line-related infection, she was started on polymyxin after sending blood cultures.

And fortunately, in 24 hours, we could grew grow a gramme-negative bacteria in the blood. Both central and peripheral blood cultures showed a gramme-negative bacteria. We have access to the blood culture identification system in our hospital. So we used it. And in the next four to six hours, less than 48 hours, we managed to identify the bacteria as Klebsiella, a group of organisms. We also managed to identify the gene mechanism which was harbouring– which the organism harboured. And this was a carbapenem-resistant Klebsiella, which had an OXA-48-like enzyme. So this was very fortuitous.

Because we stopped the polymyxin and put the patient on a combination of Ceftazidime-Avibactam, which is available now in India, which is shown to have better outcomes when used in patients with carbapenem-resistant organisms. And this was also spared the patient from the side effects of polymyxin, nephrotoxicity and the critical illness neuropathy, which would make weaning difficult. So she again responded very well. By day 14, we had to do a tracheostomy. Even though she was stable, we did not want to take a chance. She had a tracheostomy done and she continued to improve. But unfortunately, she had another setback. Close to three weeks into hospital stay, she developed, again, a low-grade fever, which persisted. The blood cultures were negative this time.

The chest x-ray did not show anything new. But because of an earlier history of tuberculosis, which was inadequately treated, we first did GeneXpert test on the endotracheal secretions or tracheal secretions to see whether it could be reactivation of tuberculosis. This patient not only had received steroids, they had also given tocilizumab when she was not responding the initial part of the illness. So a GeneXpert was done, which was negative. So we subjected her to a CT scan of the chest, which revealed several cavities, along with ground glass opacities, raising the possibility of Aspergillus infection. Now Aspergillus, as you know, is very difficult to diagnose in patients with COVID.

The susceptibility of serum galactomannan is very poor in patients with COVID, only about 20% when we compare it to influenza-associated pulmonary Aspergillosis, where it may be positive in up to 60% of cases. So in her– the serum galactomannan was was 0.75. But when we did a non-bronchoscopic sample of her respiratory secretions, we showed that the galactomannan from the respiratory secretions was 1.6. Now this doesn’t confirm Aspergillus. But it was a pointer towards Aspergillus. And using the combination of the CT scan findings, the persistent fever in spite of antibiotics, the lack of growth of bacterial pathogens, and the occurrence of galactomannan, we started her on Voriconazole. And she responded very well to Voriconazole.

So after almost a month’s stay in the ICU, we were able to wean off the ventilation. And she fortunately walked home three weeks later. So this is a very good example of how we managed to apply the local policies to patient care and also access investigations which would help us in using antibiotics wisely, especially adhering to policies of antimicrobial stewardship to ensure antimicrobial resistance is tackled. So I would like to leave you with what Mahatma Gandhi said, that a current diagnosis is 3/4 the remedy. So this case aptly illustrates that. Thank you.