“Multi-drug resistant Shigella sonnei strain has emerged the predominant serotype in Kerala”

January 6, 2021 0 By FM

Dr Anitha Madhavan, Associate Professor of Microbiology from Government TD Medical College, Alappuzha, Kerala has made a retrospective analysis of the shigella serotypes, common age groups affected and its antibiotic resistance pattern in south Kerala. The study was conducted by analysing the samples collected from all cases of dysentery and diarrhoea from January 2011 to December 2016. Among the 1,585 stool samples screened in the lab, 48 yielded shigella. The most common serogroup isolated was Shigella sonnei (62.5%), followed by Shigella flexneri. Among the 48 shigella isolates, 44 were found to be multidrug-resistant. Over the 5-year period, they found that the isolates showed 100% resistance to nalidixic acid, ciprofloxacin and cotrimoxazole. Eight of the isolates were found to be resistant to ceftriaxone and cefotaxime. So, the researchers demanded that regular monitoring of antibiotic susceptibility patterns, including detection of beta-lactamases, should be done in all microbiology laboratories and recommend that rather than a general and standardised guideline, therapy should be based on regional susceptibility reports.

Shigellosis is now in Kerala. Is there any relation between age and this disease? Is there any population which has a natural immunity to this?

Shigellosis is a global public health problem. As per reports, it is responsible for approximately 165 million cases annually, of which 98.8% are in developing countries. No individual is immune to shigellosis, but certain individuals are at increased risk. Children of less than 5 years of age are more prone to this infection, and contribute nearly 69% of cases. In our data analysis, the male gender was found to be more affected. In developing countries, it can take an endemic form.

Shigellosis has caused one death in Kerala, that of a child. Is it as deadly as it appears, or do complications arise because no treatment options are available?

Shigellosis is not deadly. But, people must be aware of the disease and use treatment facilities at the earliest. Treatment options include antibiotics and symptomatic management. Intestinal infections with shigella can be managed with rehydration, and antibiotics have proven to reduce intensity, duration, and prevent lethal complications. However, therapy involving antibiotics requires knowledge of the local antibiogram of circulating shigella strains.

Is it true that physicians are not promoting antibiotics in the treatment of shigellosis as there is a notion that shigella is developing resistance against all known antibiotics?

Yes, there are reports of the emergence of multidrug resistant shigellae with increasing resistance to third-generation cephalosporins, fluoroquinolones and most recently, to azithromycin.

Can Shigella spread through packaged food like pickles or curry powder? Or does it affect only those who have meat?

The primary mode of transmission of Shigella species is by direct contact with an infected person, fomites, contaminated food and water. The organism is acid-resistant and salt tolerant. So, there is a chance that they can spread through packaged foods like pickles or curry powder. Foods are most commonly contaminated with shigella by an infected food handler who practices poor personal hygiene. As the bacteria can be present on the surface of lavatory seats, doorknobs etc, it can take a course of infection other than through diet also.

Could you please explain how the diagnosis of shigellosis is done? How can it be differentiated from other cases of diarrhoea or dysentery?

Shigella causes both dysentery and non-bloody diarrhoea. The diagnosis of shigellosis is made by culture isolation of shigella from faeces or rectal swabs and PCR done on stool samples. The sensitivity of the PCR method is higher than those of the culture methods.

Here at Government TD Medical College Alappuzha, we have done a retrospective analysis on Shigella strains isolated from the stool culture of patients from January 2011 to December 2016. The study was conducted in the Clinical Microbiology laboratory of our hospital. Of the 1,585 stool samples processed in the laboratory, Shigella was isolated from 48 cases.

Wasr any screening for antibiotic resistance done as a part of the aforesaid study? 

Yes. Antibiotic susceptibility testing was done by the Kirby Bauer disc diffusion method on Mueller Hinton agar (HIMEDIA) as per the Clinical and Laboratory Standards Institute guidelines. The antibiotics used were ampicillin, co-trimoxazole, ciprofloxacin, nalidixic acid, furazolidone, gentamicin, and ceftriaxone (Microexpress). Of the 48 isolates, 44 isolates were found to be multidrug-resistant. Eleven isolates were resistant to six of the seven antibiotics tested. Shigella sonnei showed the highest resistance to co-trimoxazole (96%), ciprofloxacin (90%) and almost 100% resistance to nalidixic acid. On the other hand, Shigella flexneri showed higher resistance to ampicillin (83.3%) than Shigella sonnei.

How can the spread of shigellosis be controlled? 

Shigellosis is predominantly a paediatric disease in certain endemic regions of developing countries. Although infectious diarrhoea due to shigella species is self limiting in many cases, patients with positive stool cultures for shigella species should be treated to shorten the duration of the clinical symptoms and the length of shedding. The organism is shed in stool even days and weeks after the illness. But with appropriate antimicrobial therapy, cultures become negative in 72 hrs. Empiric antibiotic therapy is usually administered in children with suspected shigella infection, even while waiting for the stool culture results.

We should provide safe water supply and sewage systems; educate the people on good sanitation practices, individual hygiene and hand hygiene (fomite spread); avoid contamination of food and drinking water, and ensure the early detection and management of shigellosis to control the spread of infection.

Does the serotype of shigella affect the treatment regime? Does it  affect the curability potential of different antibiotics?

Shigella dysenteriae and Shigella flexneri are the predominant species isolated in the tropics. Among these two, Shigella dysenteriae-I is associated with large outbreaks and severe disease. Shigella flexneri is the most prevalent serogroup in other studies from India. The most common Shigella serotype obtained in our study in Alappuzha was Shigella sonnei.

A shift towards Shigella sonnei serotype, with the emergence of multidrug resistance, has been observed in other countries as socioeconomic conditions improve.

Is there any reason for the epidemic nature of shigella in a particular area in Kerala? If so, what can be the reasons?

Shigella infections are commonly associated with poor sanitation and limited access to clean water. The recent emergence of Shigella sonnei in developing countries reinforces the need for effective epidemiological surveillance systems. There should be continuing efforts by health authorities to improve sanitation and the provision of clean drinking water.

Are there any treatment guidelines issued by WHO for the treatment of shigellosis? Is it followed in Kerala also?

Antimicrobial therapy involving antibiotics can hasten the clinical recovery of shigella patients. It can also prevent its complications and check its dissemination back into the community. Fluoroquinolones were recommended as the drug of choice for shigellosis by WHO in 1990. Ciprofloxacin also proved to be highly effective in the treatment of shigellosis. The emergence of multi-drug resistance in shigella is possibly due to overuse or misuse of ciprofloxacin for diarrhoea and urinary tract infections. The resistance rate of shigella isolates to ciprofloxacin in our work came up to 85.4%. Another study from Kolkata reported about 90% resistance to quinolones. So, fluoroquinolones may not be recommended for managing shigellosis in India.

There was also a higher percentage of cephalosporin resistance in our study conducted in Alappuzha. A larger study from eight Asian countries such as Korea, Taiwan, Singapore, Thailand, Vietnam, Philippines, Hong Kong, and Sri Lanka — from 2001 to 2004 — also observed increased resistance to ceftriaxone in shigella isolates. There was a higher percentage of cephalosporin resistance (17.02%) in our study. Among Shigella sonnei isolates, 20% were found to be resistant to either cefotaxime or ceftriaxone, whereas Shigella flexneri showed 11.76% resistance. The MIC to ceftriaxone was significantly high (MIC ≥ 64). This may not reflect the true prevalence of cephalosporin resistance in Shigella, especially in the community, as ours is a tertiary care referral centre that receives partially or completely treated cases.

Why is there fluctuating resistance to antibiotics as far as shigella is concerned?

The fluctuating resistance to antibiotics in shigella may be due to plasmid mediated carriage of the resistance determinants within members of Enterobacteriaceae family. When the resistance rates of the serotypes were compared, Shigella sonnei strains were found to be more resistant than Shigella flexneri strains. The multi-drug resistant Shigella sonnei strain, which was once reported only from Israel, USA, and other developed countries, has emerged as the predominant serotype in Kerala now.

Can you please summarise the treatment options for the present Shigella outbreak in Kerala?

The present strain in Kozhikode is Shigella sonnei. As a treatment option in milder cases, especially in children, choosing the optimal oral drug is a problem and this should be based on local and updated antibiogram data. Since fluoroquinolone resistance is nearly 90%, cefixime or ceftriaxone is given in most of the health care facilities, even though it was observed that the prescription of third-generation cephalosporins as empirical drugs leads to the emergence of ESBL producing shigella strains. Azithromycin and piperacillin-tazobactam can become treatment options in dealing with multidrug-resistant strains. The most important thing is that physicians should be aware of the high antimicrobial resistance rates among Shigella. Continuous surveillance of multi-drug-resistant strains, along with serotyping, is very important to know the changing susceptibility pattern as well as cyclical changes of the serogroup in various regions of the country.