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With an antibiotic resistance crisis gaining momentum in Pakistan, the prospect of a looming medical disaster is imminent. Antibiotics designed to fight infections and block the growth of bacteria are no longer working because super bugs have developed resistance over several decades.
Problems with drug resistance are attributed to the misuse and overuse of antibiotics with the mistaken belief that they will help when administered for all kinds of infectious diseases. So why do medical practitioners continue to prescribe antibiotics — especially when not required for viral infections — or misdiagnose symptoms at the risk of increasing drug-resistant bacteria?
In a special report, we examine why antibiotics have become ineffective at an alarming rate; which common infectious diseases are easily misdiagnosed and treated with antibiotics; and why the most resistant bacteria that occur among patients at hospitals are difficult to eradicate.
Under favourable conditions, bacteria can double their numbers every ten minutes.
Pakistan’s burgeoning population is faced with a vast array of infectious diseases that can affect virtually every organ of the body — ranging from self-limiting viral infections to lethal infections of vital organs.
Environmental filth in cities, overcrowding, polluted water, animal and insect vectors, contaminated food and unhygienic personal habits create a plethora of illnesses, further perpetuated by poverty.
The myth among doctors and patients that all illnesses can be cured with antibiotics is probably one of the key reasons for the increasing propensity for antibiotic resistance.
Wrong diagnosis by doctors, medical practices by charlatans (there are over 600,000 non-registered medical practitioners in the country according to the Pakistan Medical Association), bad prescriptions, false advertisements of antibiotics by profiteers, self-medication, spurious and substandard medicines, easy sale of drugs by small-time vendors — all these factors augur poorly for the future of antibiotics, once perceived as an indispensable antibacterial weapon.
Antibiotics that previously killed bacteria are no longer effective because they have developed resistance over several decades of their use. While understanding why drug resistance has evolved, the power of bacteria becomes significant. Anyone who thinks that bacteria (germs, bugs) are nonliving, innocuous and docile detritus of earth should know that germs — like human beings — are living, breathing creatures that reproduce prodigiously and retaliate viciously when challenged.
Nature needs bacteria to perpetuate life. Trillions of harmless bacteria known as microflora coexist in the body’s cavities and on surfaces; some ‘good’ bacteria protect the body from the onslaught of harmful bacteria, while others live passively, doing neither good nor harm. In nature they maintain environmental equilibrium, break down organic garbage, feed plants and ferment foods.
Self-contained within a wall, bacterial cytoplasm constitutes genetic material that is coiled inside a chromosomal DNA, which makes enzymes as and when needed. It can store nutrients, exchange gas, reproduce, or attack human, animal or plant cells.Their small size, simple design, and diverse capabilities for survival, allow them to grow and divide rapidly, inhabit and flourish in almost any environment. Under favourable conditions, they can double their numbers every 10 minutes. Most impressively, if repeatedly provoked, bacteria can defend themselves against attack by physical and chemical agents. These single celled creatures can be a friend or a foe of the human race.
To draw an analogy of drug resistance of bacteria with the human defence system, one that is applicable to our present-day lives: imagine if thieves (read bacteria) repeatedly attacked one’s home (read body). The fear response would be to lock one’s doors and strengthen the wall.
Conversely, when bacteria repeatedly attack antibiotics, they react by strengthening their walls and closing the gaps (porins) between the layers of the cell wall. As the battle of bugs versus drugs rages, bugs produce antidotes called enzymes that neutralise the antibiotic.
Although scientists are compelled to produce more potent antibiotics to counteract bacterial enzymes, over time, clever bugs produce super enzymes, learning to transfer the information through genetic material to other bacteria of their species, and form ‘armies’ of resistant bacteria.
Some are smart enough to surround themselves with biofilms (a layer of mucilage containing a community of bacteria), preventing the penetration of drugs, similar to human body armour.
Finally, with the use of broadspectrum antibiotics or with their long-term use, hostile as well as friendly bugs are blasted and replaced with opportunistic bacteria or fungus, which become troublesome colonisers inside the host.
With antibiotics unable to eradicate bacteria, the prospect of a looming medical disaster is imminent. With the World Health Organisation ringing alarm bells, countries across the globe have woken up to this catastrophe.
Pakistan’s Federal Health Department has formed the Development of National Policy for Containment of Antimicrobial Resistance in Pakistan, of which the Medical Microbiology and Infectious Disease Society of Pakistan is a component and has offered solutions.
The MMIDSP strongly advises that the issue be understood at the public health level and by physicians. Infectious diseases (ID) are highly prevalent, but the subject is not taught didactically in most medical colleges — rather, it is merged with other disciplines.
Because ID is a dynamic specialty with ever-expanding frontiers, new and emerging IDs, innovations in diagnostics, prevention and treatment, it must be embedded in the curriculum of all medical schools, and even, perhaps, be initiated in schools.
Regrettably, prescription writing of antibiotics is encouraged and dictated by vested partners of the pharmaceutical industry, for whom unlettered medical practitioners and charlatans are sitting prey. Patients, too, should realise that antibiotics are not the panacea for all fevers, and, must desist from self-medication, or expect a prescription from their caregivers.
Each antibiotic has a specific property, mode of action and variable effect against different bacteria. Antibiotics are not antivirus, rather, the body’s system is harmed, side effects develop, diagnosis is compounded, and the cost of investigation and treatment rises to exorbitant amounts.
Multi-drug resistant tuberculosis, for instance, is becoming increasingly prevalent, and requires treatment with expensive and toxic drugs for up to two years to cure.
Typhoid, a serious but common community infection, has so far been treatable with oral antibiotics. However, alarming reports of drug-resistant typhoid are beginning to emerge, and its mode of treatment is uncertain at this time.
The most resistant bacteria occur in hospitalised patients, which are acquired from other patients, hospital personnel or contaminated equipment, especially in surgical operating rooms and critical care units.
Furthermore, hospital acquired infections are increasingly difficult to eradicate and often cause death. The obvious solution to mitigating the scourge of drug resistance is to prevent infection.
And there is no better solution than disease awareness, a clean environment, hygienic personal habits, correct diagnosis and prudent drug prescription.
The writer is the head of the division of infectious diseases at the Indus Hospital in Karachi. She can be reached at firstname.lastname@example.org.
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Growing drug resistance is one of the biggest public health threats of modern time.
For patients like Shireen, even the strongest drugs don’t work.
Having suffered from a debilitating ear infection for the past four years, Shireen, only in her teens, has recently been admitted to the Jinnah Postgraduate Medical Centre (JPMC), one of the largest public tertiary care hospitals in Karachi.
Shireen has travelled for treatment to Karachi several times from a remote village in Lasbela District, Balochistan. But multiple visits to doctors have only brought temporary relief.
“My ear hurts, leaks pus and, at times, even blood. The doctor recently told me that I need an operation,” she says worryingly.
Awaiting surgery for a similar health problem in the ear, nose and throat (ENT) ward is Asma, the eldest of five siblings from North Karachi. Her ear infection has been recurring for eight years.
“I’ve been taking medicines for a long time but the infection keeps recurring or, perhaps, it has never gone. I don’t know whether my frequent headaches and failing vision have something to do with the ear infection, too,” she says.
Both girls quit studying because of their chronic illness. For them, their ill health is also a source of psychological trauma, missing out on the productive years of their life.
It’s hard to measure their anguish, but what is also disturbing is that these girls are among many patients visiting hospitals every month with serious health complications following prolonged misdiagnosis by local doctors or, in certain cases, quacks.
These health complications have much to do with the misuse of antibiotics, including the prescription of antibiotics for viral infections against which they have no effect, frequent prescription of antibiotics as well as inadequate use by patients.
According to Dr Naushad Langha at JPMC, local general practitioners (GP) should have referred both girls directly to an ENT specialist instead of prescribing different antibiotics without reaching a diagnosis after laboratory tests.
“The misuse of antibiotics helps the infecting bacteria develop resistance against the same drugs meant to kill them. In their [Shireen and Asma] cases, the infection has spread to a point that it can affect the brain, if all the diseased areas are not surgically removed.”
According to him, “the severity of their condition is directly linked to the resistance shown by the infecting bacteria towards multiple antibiotics. This fails to improve their condition with medicines.”
Local practitioners often lack specialised equipment for a detailed examination, and should refer patients with recurring illnesses to relevant specialists, Dr Langha suggests.
More importantly, because the majority of patients who visit public hospitals are poor and illiterate, they must be given proper medical guidance regarding diagnosis and treatment.
Apart from the trauma that patients and their families face, increased resistance of germs against antibiotics limits treatment options, raising costs of hospitalisation, he points out.
For his part, Dr Tariq Rafi, an ENT specialist, explains that bacterial and viral infections can cause similar symptoms, and it’s the responsibility of a doctor not to prescribe an antibiotic unless there is a clear evidence of a bacterial infection.
“A sore throat is viral in 80 per cent of cases and bacterial in only 20pc. This means a patient with a viral sore throat infection only needs medicines to alleviate his or her symptoms,” he said.
Viral infections, particularly of the upper respiratory system, experts say, are usually self-limiting; they go away on their own after few days or weeks and antibiotics have no role in their cure. The frequent use of wrongly prescribed or substandard antibiotics only helps bacteria develop resistance against drugs.
So why do physicians prescribe antibiotics unnecessarily, or even misdiagnose symptoms? Doctors speaking on condition of anonymity blamed their own community for this health disaster.
“Often, doctors don’t want to lose a patient looking for a quick recovery. Then, there are many practitioners who receive incentives from pharmaceutical companies for prescribing their antibiotics,” a senior doctor at JPMC told Dawn, adding that the government, too, shared responsibility, having failed to restrict the easy availability of antibiotics.
The widespread and inappropriate use of antibiotics is not just restricted to local GPs; it is common even in hospitals, which are hotspots for infections.
According to health experts, one reason for the spread of organisms that have multidrug, or antimicrobial, resistance (MDR) in communities is a lack of hospital waste management as most waste is dumped in the water supply system, infecting people with MDR germs.
Hospitals often amplify the spread of infections if they lack infection control practices.
Because healthcare facilities are apt environments for germs to evolve and develop MDR as patients with all kinds of illnesses visit and are treated by the same staff, infections acquired in hospitals are far more serious than others.
Dr Altaf Ahmed, director of infection control at Indus Hospital in Karachi, says this makes medical facilities the riskiest places for vulnerable patients.
He believes the MDR trend in Pakistan is similar to what is being observed in other countries, but the severity of the situation is alarming given a weak health system with poor access to quality diagnostic facilities.
“Annually, 90,000 people die as a result of hospital-associated infections in the US, but given the general hospital environment in Pakistan, one can imagine the issue would be of grave concern here,” he said.
It is essential, therefore, that medical staff disinfect their hands before examining patients — a practice that must be enforced more rigorously, including the use of disinfectants and the sterilisation of equipment.
On a recent visit to a local private hospital, we were informed that there were a number of patients who had acquired serious infections while being treated in the hospital.
Resultantly, some were on ventilators and battling for their lives, while families often remained unaware of how they had contracted serious illnesses.
Hospital acquired infections occur up to 48 hours after hospital admission, up to three days after discharge and up to 30 days after an operation.
One of the most common areas for contracting such infections is in the intensive care unit (ICU). Such infections are associated with serious morbidity, mortality and, of course, hospital costs.
Referring to the threat posed by MDR to the survival of newborn infants, an article published in 2016 in The Lancet titled ‘Antimicrobial resistance: a threat to neonate survival’ notes that an estimated 25,692 newborn infants die annually in Pakistan (56,524 in India) from resistance-attributable neonatal sepsis deaths caused by bacteria resistant to first-line antibiotics.
In the absence of official data, it is hard to assess the national burden of morbidity and mortality because of MDR. However, independent studies by various healthcare facilities provide evidence of the increasing presence of MDR infections.
“These reports indicate that MDR is becoming a leading cause of treatment failures in Pakistan, especially for tuberculosis, typhoid fever (a recent outbreak in Hyderabad had to be treated with a very highly reserved antibiotic), urinary tract infections (caused by E. coli and K. pneumoniae), ventilator associated pneumonia in hospitals (caused by MDR organisms, the leading causes of death in ICUs) and sexually transmitted diseases (caused by N. gonorrhoea and treatable only by injectable antibiotics),” says Dr Erum Khan, an associate professor of pathology and laboratory medicine at the Aga Khan University Hospital.
She believes testing methods for antimicrobial susceptibility tests must be standardised.
“The fact that most laboratories in Pakistan do not follow international guidelines on good laboratory practices is a major impediment in assessing the antimicrobial resistance (AMR) burden and its control,” she explains.
This implies lack of legislative control and resources.
On its part, the Aga Khan University is involved with developing a national action plan for AMR control, an initiative spearheaded by the government in collaboration with the World Health Organisation (WHO).
According to WHO, tuberculosis is a major health problem in Pakistan, estimated with the fourth highest prevalence of MDR TB in the world.
“The problem is real and very disturbing. MDR results in a lack of oral options, and doctors are forced to use expensive and intravenous antibiotics. Our staff at the Sindh Institute of Urology and Transplantation face the challenge of managing infections with MDR organisms on a daily basis,” says Dr Asma Nasim, an assistant professor at the department of infectious diseases.
In an SIUT study, 48pc out of the 243 patients tested had a blood stream infection with one or more MDR organisms.
“Half of the patients infected with MDR bugs made for an alarming situation. This means more patients with an increase in cost, which the hospital has to bear (SIUT provides free treatment). We also found that mortality risk increases in patients with MDR bugs as compared to infections with sensitive organisms (40pc versus 27pc),” she adds.
While scientific data emerging from Pakistan is alarming, neither the health ministry nor the provincial governments have shown signs of taking action beyond planning interventions.
However, Dr Mohammad Salman, the national focal person for AMR control explains that the health ministry has developed a national strategic framework on AMR control with expert assistance and with relevant stakeholders.
“We are in the process of finalising a national action plan on AMR control to act as a guideline for all provincial governments,” he says, adding that the ministry will provide technical support to the provinces. The latter will have to develop independent plans for AMR control.
Although national efforts on AMR control follows the 2015 World Health Assembly resolution which endorses a global action plan to tackle antimicrobial resistance, including antibiotic resistance, the government has their work cut out for them.
Measures that are urgently required include: awareness campaigns (among the public as well as health professionals) on the misuse of antibiotics and prevention of MDR infections; improvement of rapid diagnostics; physician training to limit prescriptions; and legislation to prevent over-the-counter prescriptions.
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A study by the Institute of Environmental Studies at the University of Karachi found that most food items sold around several public hospitals in the city were contaminated with various disease-causing bacteria, almost all showing resistance against commonly used antibiotics (MDR), and therefore unfit for consumption.
The study tested samples of food sold inside and outside ten public hospitals during the period from September 2015 to May 2016. These were analysed to detect various bacteria and to test the quality of food. According to the World Health Organisation, there should be no trace of bacterial contamination in food consumed.
According to Dr Moazzam Ali Khan, who supervised this study, the findings are alarming and indicate how rapidly MDR bacteria are polluting the environment.
Food samples tested included bun kebabs, chanay ki chaat, samosas, fried vegetables, chicken rolls and pakoras sold by street vendors outside Civil Hospital Karachi, Landhi Medical Complex, Abbasi Shaheed Hospital, Sindh Government hospitals (centers situated in Liaquatabad, Qatar and UP More), Lyari General Hospital, Jinnah Postgraduate Medical Centre, Dow University of Health Sciences (Ojha Campus) and Sindh Social Security Hospital.
The TAC (an indicator of bacterial load in a food sample), for example, was as high as 2,400 MPN per 10gms in all samples of bun kebabs tested except for those collected from Landhi Medical Complex. The same count was found in chaat and samosa samples. It was found that most food samples were contaminated with coliforms (bacteria that are present in the digestive tracts of animals and humans, and are found in their wastes).
Explaining how MDR germs made their way into food sold near these hospitals, Dr Khan said that the dumping of waste (especially medical waste) in the open, the lack of infection control measures in hospitals, the mixing of sewerage lines with the main water pipelines and poor hygiene practiced by food sellers were major contributors to the evolution of germs and their spread.
“The unhygienic environment in which this food is prepared and handled contributes to bacterial contamination, posing a serious threat to all outpatients and inpatients who might consume food from such sources,” he said.
Hospital waste is improperly disposed of because most health facilities in the country do not have a waste management system, says Dr Qaiser Sajjad, general secretary of the Pakistan Medical Association.
“Hospitals that do claim to have a system are unable to run it properly, either because the system is obsolete or there are no funds to run it.”
There is a dire need for respective provincial governments to look into the issue and set up at least one facility in every district to treat medical waste.
“Unregulated medical waste is a serious public health hazard as it contains all kinds of disease-causing germs. The most critical point in this case is the non-segregation of waste at the source. This practice makes 80 per cent of non-hazardous waste, including domestic refuse, infectious when it is mixed with 20pc of harmful medical waste dumped openly by healthcare facilities,” he explains.
Provinces do have regulations on hospital waste management, but there is hardly any implementation.
“The operation of clinics and maternity homes in every neighbourhood without a proper system for waste disposal is a source of spreading communicable diseases,” he said, adding that, besides municipal corporations, it’s also the responsibility of environmental protection agencies to monitor waste treatment and disposal in the city.
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According to the World Health Organization (WHO), multidrug resistance (MDR) is globally prevalent due to overuse or misuse of antibiotics in humans and animals. Antibiotics are often misused as growth promoters in animals and fish.
Microbes with MDR are found in humans, animals, food – and in our water, soil and air – and can spread between people and animals, and from person to person. Poor infection control, sanitary conditions and food-handling encourage the spread of MDR.
Studies suggest 20 to 50 per cent use of antibiotics in hospitals and communities (by general practitioners) is unnecessary, while 40 to 80pc use of antibiotics in the livestock sector is highly questionable. In the absence of any regulatory mechanism, it is likely that the situation in Pakistan is similar, if not worse.
However, a senior expert believes that livestock farmers take due care when their animals require treatment.
“They [farmers] have made an investment and they won’t do anything which would result in a loss. So prescription drugs recommended by a veterinarian are used and self-medication is largely avoided,” he says.
The usage of antibiotics for growth is only practiced in the poultry industry, as organised stall-fed livestock farming for mutton and beef production is largely not practiced in Pakistan.
“In poultry, farmers use antibiotics as a prophylactic treatment to prevent infections in young birds, which is termed as growth promoter to some extent. So, we can say there is some sort of judicious use of antibiotics in the livestock sector as a whole,” he explains.
Efforts are being made to introduce antibiotic replacement products as antimicrobial agents in view of recent restrictions imposed, especially by the European Union, on the usage of antibiotics in livestock rearing.
“It will not be possible to export any product of animal origin to these countries until it is free from drug residues,” he says, adding that currently there is significant use of antibiotics in the agriculture sector.
The health ministry is in the process of developing an action plan for executing a proposed antimicrobial policy, after which it will be possible to follow WHO principles on MDR.