When antibiotics fail

Cooperation against antimicrobial resistance urged to save more lives

ANTIMICROBIAL resistance (AMR) could take 10 million lives annually by 2050, unless the health-care sector, governments, stakeholders and the people work together fast to address this challenge, experts warned.

The magnitude of this global threat over the next 30 years, based on a report prepared by the United Nations Ad hoc Interagency Coordinating Group on AMR, was raised by Pfizer Philippines Country Brand Lead Rene Carlo B. Pascual at a recent media roundtable discussion as part of the observance of World Antibiotic Awareness Week, which runs until November 24, 2019.

“This is not because of a natural calamity, not because of an earthquake, not because of a typhoon, but it’s another phenomenon which we can [already deal with] today,” he said.

AMR among microorganisms, such as bacteria, viruses and fungi, is mainly caused by improper use of antibiotics. This leads to infections being incurable and at a high risk of spreading to others.

“Simply put, it’s when you have a group of bugs…which [was] previously [treated] when you used [an] antibiotic, it would kill the bug and, in effect, it will be able to treat the infection. But if you have antimicrobial resistance [and if] you use the same antibiotic…it’s not able to kill the bug. Hence, you don’t get better from the infection,” explained Dr. Ma. Charmian M. Hufano, medical consultant in internal medicine and infectious diseases at De Los Santos Medical Center (DLSMC) and St. Luke’s Medical Center.

Approximately at least 700,000 people die each year due to drug-resistant diseases, per the latest UN report. Apart from humans, AMR also affects animals and the environment.

Improper use of antibiotics

HEALTH professionals agree that inappropriate use of antibiotics could be partly blamed for the rise of AMR worldwide.

Citing the study of the World Health Organization (WHO) on how antibiotics are being used in primary care in developing and transitional countries that included the Philippines from 1990 to 2006, Hufano revealed that more than 50 percent of antibiotic prescriptions were identified as “inappropriate,” or “given at the wrong dose, at the wrong duration, or for the wrong indication.”

If the so-called “antibiotic selective pressure” brought about by the use of antibiotic appropriately and inappropriately becomes very strong, the acquisition of drug resistance becomes faster, Hufano noted.

“So we are faced with the possibility that there will be not enough antibiotics to treat even common infections,” she cautioned.

The Clinical Infectious Diseases journal reported in 2008 that the recent number of new antibiotics launched in the market is lower compared to the early years. It showed that there were 16 antibacterial agents made available in the market from 1983 to 1987; 14, from 1988 to 1992; 10, from 1993 to 1997; 7, from 1998 to 2002; 5, from 2003 to 2007; and 2, from 2008 to 2012.

“Less and less new antibiotics are being introduced. So this is what we forecast if nothing is done about this,” said Hufano, who is also the chairman of the Department of Medicine and the Committee of Antimicrobial Stewardship at Dela Salle Medical Center (DLSMC).

Another negative effect of improper use of antibiotics, she said, is the possibility that these medications will no longer work when used to treat patients with drug-resistant bugs. Given this, the average nine-day hospital stay after diagnosis and 36.4-percent hospital mortality rate for patients who have severe infections treated with appropriate antibiotics increases to 11 days and 51.7 percent, respectively, if given inappropriate antibiotics, per the study on Critical Care Med done in 2011.

Local vs global communities

HEEDING the WHO’s call for member-nations to come up with their own AMR study, the Department of Health (DOH) created the Philippine Committee on Antimicrobial Resistance Surveillance Program (ARSP) in 1998.

This initiative aims to provide critical inputs to the DOH’s effort to promote rational drug use by identifying the status and developing trends of AMR of selected bacteria to specific antimicrobials. At present, 24 sentinel sites and two gonorrhea surveillance sites joined the program, representing 16 regions nationwide.

From the 2018 Annual ARSP Report, different community- and hospital-acquired pathogens were examined. Among them is the Methicillin-resistant Staphylococcus aureus (MRSA) that is resistant to all penicillin, cephalosporin and carbapenem. For last year, the MRSA rate was at 53 percent.

“This means that for every two patients with this bug and this infection, one will already be resistant to that antibiotic. So this is really problematic,” she said. “And it differs from every hospital that we have in the surveillance. Some rates can be as high as almost 80 percent in one hospital to lowest, I think in these data, [it] is at 32 percent. So even at the lowest data, still one out of three would already be resistant to that set of antibiotics.”

Benchmarking the local data from other countries in 2017, the rate of that type of drug-resistant bug in the Philippines was at 56 percent, compared to Japan at 41 percent, Korea at 53 percent, Vietnam at 73 percent, Thailand at 17 percent, and the United Kingdom at 7 percent. “So it’s doable to have low rates of resistance,” Hufano said.

Another bug covered in the surveillance last year was the Escherichia coli (E. coli), which is the common cause of urinary tract infections (UTIs),  among others. She stated that it’s likewise “very problematic” here since it is present both in the hospital and community settings.

From a list of common oral antibiotics used to treat UTI in outpatients, E. coli’s resistance rate to ampicillin is at 78.1 percent; amoxillin-clavulanic acid, 24 percent; cefuroxime, 36.5 percent; ciprofloxacin, 45.1 percent; trimethoprimsulfamethoxazole, 57.8 percent; nitrofurantoin, 4.8 percent; piperacillin-tazobactam, 4.8 percent; ceftriaxone, 34.4 percent; ertapenem, 0.9 percent; and amikacin, 3.7 percent.

The third generation or multidrug-resistant version of the E. coli called “cephalosporins” is also problematic here and abroad. Its antibiotic resistance in the Philippines was at 49 percent two years ago, whereas in the UK it’s only at 11 percent, Japan at less than 30 percent, and Korea at around 35 percent. Its resistance rate is very high in India at 77 percent. In terms of its resistance to carbapenem, it’s only at 5 percent here, whereas in Vietnam and India, it’s at 6 percent and 18 percent, accordingly.

Klebsiella pneumoniae is the most common organism in the report every year because it is seen both in the hospital and community setups. It’s very similar to E. coli in terms of drug-resistance profile.

Based on the resistance level of this bug in the DOH-ARSP report in 2018, around 10 percent of it will be resistant to the broad-spectrum antibiotics available to treat it.

Meanwhile, from the 2017 data, its resistance to cephalosporins is at 65 percent in the country versus 6 percent in Japan; India had the highest rate of 68 percent. When it comes to its resistance to carbapenem, Klebsiella in the Philippines was at 17 percent compared to Vietnam’s 24 percent and India’s 59 percent.

Ubiquitous organism Pseudomonas aeruginosa is very difficult to combat. It is common in patients who are very sick, or have other illnesses that make their immune system very weak.

The medical consultant in internal medicine and infectious diseases said that Pseudomonas is usually resistant to multiple antibiotics at the same time. In the 2017 data from ARSP, she added that it was 21-percent resistant to at least three classes of antibiotics all at the same time.

The antibiotic resistance of this bug is at 22 percent in the Philippines, lower than Vietnam (36 percent), South Africa (30 percent), India (30 percent), but higher than the US (10 percent), the UK (8 percent) and Australia (8 percent).

“I think we get the picture here. Inappropriate antibiotics is one of the biggest drivers for antimicrobial resistance, and antimicrobial resistance is a major public health issue not just globally but obviously locally, and multidrug resistance is seen both in the community and hospital settings,” Hufano said.

Vaccination as solution

As with any health problem, AMR costs money, livelihood and lives. More so, it threatens to compromise the effectiveness of health-delivery programs.

“AMR affects everyone, any age, any social class, all over the world. It is a worldwide challenge,” said Dr. Rontgene M. Solante, former president of the Philippine Society for Microbiology and Infectious Diseases (PSMID). “That is why programs by the DOH, and under the Universal Healthcare law, include the proper distribution, administration, and taking of antibiotics. We need to be responsible as health-industry workers; and the public, as people who consume medicines [must also be responsible].”

The infectious disease specialist likewise emphasized the importance of vaccination in reducing the prevalence and impact of AMR in the country. An example is Streptococcus pneumoniae vaccine.

“We call that the ‘pneumococcal’ vaccine because the most common manifestation is pneumonia—respiratory tract infection. So if you give someone a pneumococcal vaccine, you will prevent that person from getting a respiratory tract infection. Since respiratory tract infection because of pneumonia entails the use of antibiotics, it will also cause drug resistance when you give an antibiotic,” he said.

Globally, the most common source of Streptococcus pneumoniae are the infants. Thus, in the US, when the government vaccinated most of the children with it, a decrease in pneumonia among the elderly, even those who were not immunized, was observed.

To achieve the benefit of this so-called “herd immunity,” there is a need to vaccinate 70 percent of the children’s population. Sadly in the Philippines, the number of kids given with Streptococcus pneumoniae vaccine is quite low.

“It’s [only] 10 percent because we cannot afford this vaccine. It’s very important, plus the fact that we have problems of low vaccination rate because they don’t go to the [health] center. So that adds up [to] why pneumonia is an important cause of drug resistance,” Dr. Solante revealed.

Immunization is really important, hence it is recommended to be administered at an early age. He explained: “When you vaccinate, first, you prevent development of infection, so no prescription. Second, [if] you reduce the prescription, you reduce drug resistance. Third, when you vaccinate, you reduce the transmission of the infection, so nobody gets infected. Fourth, you reduce carriage because the source of the infection is in your nasopharyngeal area. And then it’s also effective against resistant strain because it will now promote the reversion from a resistant to a susceptible strain because you are given the vaccine.”

From an economic point of view, vaccination also leads to less death rates and less hospitalization of the people that, in turn, helps the government save money through the Philippine Health Insurance Corp. (PhilHealth), which subsidizes the health-care need of  the populace.

Per the 2017 “Economic Burden of Community-Acquired Pneumonia (CAP) Among Pediatric Patients (Aged 3 Months to Less Than 19 Years) in the Philippines” research by the group of Dr. Bernadette Tumanan-Mendoza of Manila Doctors Hospital, the health-care cost of an infant patient admitted in a private hospital would be around P50,000 to P60,000, of which PhilHealth only covers about P15,000.

“So the point here is, if this is the cost of hospitalization of a pediatric patient, P24,000 to P75,000, and PhilHealth will only pay P15,000, the excess amount will be a burden to the patient. If this is the amount that PhilHealth will pay [for]  severe pneumonia, because this is the cost of hospitalization—P121,000 in a private hospital—but PhilHealth will only pay P32,000, that’s a big burden on the part of the patient and of the government.”

This revelation flies in the face of data showing pneumonia has been identified as the No. 1 disease that PhilHealth pays for among the hospitals. The government-owned health insurer paid P1 billion in claims for CAP based on PhilHealth case rate; P14 billion in 2018; and P14 billion, first half of 2019.

“So the advocacy for Universal Healthcare, part of that is also prevention. And that has been stipulated in the framework of Universal Healthcare [law],” said the infectious disease expert of San Lazaro Hospital.

Citing the cost-utility analysis of pneumococcal conjugate vaccines (PCV) in the Philippines conducted by PSMID, President Manuel Alexander Haasis, et al., Solante recommended the inclusion of PCV in the national immunization program, particularly PCV13, which achieved better value for money compared to PCV10. He noted, though, that the affordability and sustainability of PCV implementation in the long run must be considered by decision-makers.

“Per the total economic cost [of PCV], it will be beneficial [to all]. This has to be the priority of the government,” he stressed.


PFIZER is one of the signatories of the Davos Declaration in 2016 during the World Economic Forum (WEF) in Switzerland, committing itself to join in the collective efforts of companies in the pharmaceutical, biotechnology and diagnostics industries for a sustainable market for antibiotics, vaccines and diagnostics.

“So you want to reduce the development of resistance, you want to invest in research and development related to global public health needs, as well as improve access to these high-quality antibacterials that come out from these companies,” is how the bottom line is laid down by Dr. Evan Payawal, senior medical manager, Pfizer Anti-Infectives. “We are serious about participating in this [declaration].”

Pfizer, with other pharmaceutical firms, promotes the Roadmap for Progress on Combating Antimicrobial Resistance, using a six-part strategy: stewardship, manufacturing, surveillance, vaccination, a supportive regulatory framework, and incentives and new business models to support research and development and a sustainable marketplace.

The pharmaceutical giant, likewise, called on not only health workers but also the general public to join the fight against the spread of AMR and be involved in international antimicrobial stewardship through simple acts like making sure that they follow directions on the package, taking antibiotics only as prescribed by doctors, and frequent hand washing.

“At Pfizer, we are driven by our desire to protect global public health and address the medical needs of people suffering from infectious diseases. We are committed to being a leading provider of solutions to both help prevent and treat infections through antimicrobial stewardship,” he said.

At present, the company offers one of the industry’s largest and most diverse portfolios of anti-infectives, that includes more than 80 medicines. This portfolio contains therapies that help address areas of greatest unmet medical need.

Image Credits: Skypixel | Dreamstime.com, Designua | Dreamstime.com

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