Invasive group A strep: are prophylactic antibiotics key?

“No cases of iGAS disease were recorded for dialysis patients prescribed regular [trimethoprim–sulfamethoxazole (TMP/SMX)] during the wet season melioidosis prophylaxis period. Wet season iGAS disease incidence among Top End people receiving haemodialysis but not prescribed TMP/SMX at diagnosis was 1122 (95% CI, 412–2441) cases per 100 000 patients.”

NORTHERN Territory researchers have raised consideration of year-round antibiotic prophylaxis for at risk haemodialysis patients in the region after they found encouraging data suggesting the possibility of greatly reducing invasive group A Streptococcal (iGAS) disease in that population.

iGAS causes substantial morbidity and mortality in the NT, particularly in First Nations populations, especially in those undergoing haemodialysis.

Dr Johanna Birrell, from the Northern Territory Centre for Disease Control, told InSight+ in an exclusive podcast that group A streptococcal (GAS) disease was “a disease of inequity”.

“GAS may manifest in a number of different ways,” she said.

“It can cause superficial infections like pharyngitis and impetigo, or it can become invasive when areas of the body that would usually be sterile become infected, such as in sepsis.

“The severe end of the spectrum includes necrotising fasciitis, but there is a whole range of other manifestations, such as pneumonia, endometritis, septic arthritis, osteomyelitis and internal organ abscesses.

“It can also have post-infectious complications, especially in children, like acute rheumatic fever, and post-streptococcal glomerulonephritis.”

Since iGAS became notifiable in the NT in 2011, the reported incidence has been around 34 per 100 000, “which is really high compared with other jurisdictions, but with even higher rates of around 100 per 100 000 in First Nations Territorians”, said Dr Birrell.

One manifestation of GAS is skin infections such as impetigo, which may be why haemodialysis patients are at risk of iGAS disease.

“We don’t have a complete understanding of why this group are at such extremely high risk [of iGAS],” said Dr Birrell. “Most likely it’s a combination of higher rates of advanced diabetes, peripheral vascular disease, being immunocompromised and repeated needling through the skin at each dialysis session. Then, commonly, social disadvantage and overcrowded living conditions are contributing as well.”

Since November 2014, patients undergoing haemodialysis in the NT have received antibiotic prophylaxis for melioidosis after each dialysis session (three times a week) during the wet season. Melioidosis is an infectious disease that causes “a very diverse clinical spectrum ranging from simple skin infections to pneumonia to disseminated disease with fulminant septicaemia”. It’s endemic to northern Australia and peaks in the wet season.

The antibiotic chosen for melioidosis prophylaxis in dialysis patients is oral trimethoprim–sulfamethoxazole (TMP/SMX), which also happens to have activity against GAS.

Dr Birrell and her colleagues identified cases of iGAS disease diagnosed during 1 May 2011 – 30 April 2021 in the NT Notifiable Diseases System and retrieved the corresponding electronic health records. Antibiotic prescribing data were obtained from the NT Enterprise Data Warehouse. Population data were retrieved from the NT Health Renal Unit and Population and Digital Health Unit.

“A total of 692 cases of iGAS disease were identified; 511 patients were Indigenous Australians (74%), 380 were women (55%), and 131 were receiving haemodialysis (19%),” Birrell and colleagues reported in the MJA.

“GAS was cultured from blood in 652 cases (94%). Of the 378 cases for which severity was reported, 135 met the criteria for severe iGAS disease (36%). Thirty-day all-cause mortality was 6% (40 deaths). The overall age-standardised incidence of iGAS disease in the NT during the study period was 34.3 (95% confidence interval [CI], 31.4–37.1) cases per 100 000 population [and] … was higher for Indigenous than non-Indigenous Territorians in all age groups.

“Of 626 people receiving haemodialysis in the Top End, 506 (81%) were prescribed TMP/SMX melioidosis prophylaxis during 1 November 2014 – 30 April 2018. The annual proportion has increased since the initiation of routine prescribing (data not shown). TMP/SMX was prescribed on 183 625 of 451 346 wet season haemodialysis patient-days (41%).

“No cases of iGAS disease were recorded for dialysis patients prescribed regular TMP/SMX during the wet season melioidosis prophylaxis period,” they reported.

“Wet season iGAS disease incidence among Top End people receiving haemodialysis but not prescribed TMP/SMX at diagnosis was a staggering 1122 (95% CI, 412–2441) cases per 100 000 patients.”

Dr Birrell said the findings had significant implications for regions with high rates of iGAS disease.

“There’s a potential role for year-round antibiotic prophylaxis in people with the highest risk of iGAS, who are those receiving dialysis in the NT,” she told InSight+.

“This might potentially save lives and prevent many hospitalisations, intensive care unit admissions and morbidity.”

One downside is the prospect of potential antimicrobial resistance developing with increased antibiotic use.

“Antibiotic prophylaxis also carries risks of its own, like adverse drug reactions, potential antimicrobial resistance, and there’s a financial cost to the medication,” said Dr Birrell.

“Our findings warrant a prospective trial, and a thorough and holistic analysis of the pros and cons of the prophylaxis – including input from stakeholders, including feedback from patients, particularly those receiving dialysis and their thoughts on continuing antibiotics year round. Also the impact on other infections and factoring in adverse medication event rates such as seen in the melioidosis cohort so far. Most importantly, there is a need for greater investment in improving the social determinants of skin health, to decrease the high rates of underlying impetigo in dialysis patients and others.”

Despite being notifiable in the NT since 2011, iGAS disease only became nationally notifiable in July 2021.

“We’d be recommending to our colleagues elsewhere in Australia and overseas to look at their rates of invasive group A strep in their dialysis patients,” said Professor Bart Currie, from Royal Darwin Hospital and the Menzies School of Health Research, and a co-author of the MJA research.

“Other public health units around the country can now look at their dialysis patients and see whether their [GAS and iGAS] rates are as high as ours are and, therefore, whether they want to consider this as well.

“We also are very aware that when you use a lot of [TMP/SMX], very occasionally you will get severe cutaneous adverse reactions, so we don’t use it lightly.”

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