Antibiotic Resistance

Key Evidence: A meta-analysis of antimicrobial resistance (AMR) in migrant populations in Europe found that 25% of migrants carried or were infected with antibiotic resistant organisms. When considering all migrant types, refugees and asylum seekers had a higher rate (33%) of carrying or being infected with AMR organisms than other migrant groups (7%).

Key Evidence: A large U.S. study of surveillance data examining the impact of switching from PCV7 to PCV13 for infants demonstrated how important vaccination is in combating antimicrobial resistance. While the incidence of antibiotic-resistant invasive pneumococcal disease (IPD) was increasing before the introduction of PCV13, drug resistant IPD declined 78-96% in children under five after the vaccine introduction.

Key Evidence: This study from South Africa demonstrates significant declines in invasive pneumococcal disease cases caused by bacteria that are resistant to one or more antibiotics. In fact, the rate of infections resistant to two different antibiotics declined nearly twice as much as infections that could be treated with antibiotics.

Key Evidence: Following the introduction of PCV7 and later PCV13 in Madrid, Spain, there was a 70% reduction in the incidence of invasive pneumococcal disease in children less than 15 years of age. There was also a pronounced decline in the percentages of penicillin- and cefotaxime-resistant strains of the pneumococcus bacteria. After PCV13 was introduced in 2010, cefotaxime resistance among meningitis patients completely disappeared and both cefotaxime and penicillin resistance among non-meningitis cases declined to very low levels (<3%).

Key Evidence: Studies in several countries have shown that, following the introduction of pneumococcal conjugate vaccine, there was a reduction in the number and percent of drug-resistant cases of pneumococcal diseases in children, and in some countries in adults, due to herd effects. In Japan there was a 10-fold decline in the proportion of penicillin-resistance among cases of invasive pneumococcal disease (from 56% to 5%), and in the U.S. there were reductions of 81% and 49% in the proportion of penicillin-resistant cases in children less than two years and in adults more than 65 years old, respectively.

The 2010 introduction of PCV10 for infants in Finland led to an estimated 15% reduction among unvaccinated children in purchases of antimicrobials recommended for acute otitis media (AOM), the most common reason for antimicrobial use in many countries. The indirect effects of PCV10 introduction contribute to health care savings and may also help to combat antimicrobial resistance.

Key Evidence: A retrospective observational register-based study found that the 2010 introduction of PCV10 for infants in Finland led to an estimated 15% reduction among unvaccinated children in purchases of antimicrobials recommended for acute otitis media (AOM), the most common reason for antimicrobial use in many countries. The indirect effects of PCV10 introduction contribute to health care savings and may also help to combat antimicrobial resistance.

Key Evidence: A study of sickle cell disease patients in Ghana found that pneumoccocus bacteria found in their noses and throats had high rates of drug resistance with 37% of positive samples resistant to penicillin and 34% resistant to multiple drugs (typically penicillin + tetracycline + cotrimoxazole).

Key Evidence: Among both HIV positive and HIV negative parents in a study in Kenya, 99% of pneumococcal strains found and tested were resistant to one or more antibiotics. HIV positive parents carried 16% more strains that were resistant to penicillin than those carried by HIV negative parents.

Key Evidence: Two years after the introduction of 10-strain pneumococcal conjugate vaccine (PCV-10) in Kenya, the percent of HIV-positive adults who carried pneumococcal bacteria declined significantly (from 43% to 28%), but did not decline in HIV-negative adults. However, the reduction in carriage of pneumococcal strains that are in PCV10 declined significantly in both HIV-positive and HIV-negative adults. This reduction was still four times higher in HI- positive vs. HIV-negative adults (2.8% vs. 0.7%), indicating that HIV positive adults continue to be at considerably higher risk of invasive pneumococcal disease than HIV-uninfected adults.

From the VoICE Editors: Nasopharyngeal carriage is an indicator of the risk for invasive pneumococcal disease and pneumonia. 

Key Evidence: In this analysis of data from large-scale studies of households, two vaccines recently implemented in the WHO EPI, pneumococcal conjugate vaccines and live attenuated rotavirus vaccines, were estimated to confer 20% and 11% protection against antibiotic-treated episodes of acute respiratory infection and diarrhea, respectively, in the age groups with the greatest disease burden attributable to these pathogens. Under current coverage levels, pneumococcal and rotavirus vaccines are estimated to prevent 24 million and 14 million episodes, respectively, of antibiotic-treated illness each year among children in LMICs less than five years old. An additional 40 million episodes could be prevented through achievement of universal coverage targets.

Key Evidence: Evaluation of the ability of pneumococcal conjugate vaccine to reduce the occurrence of respiratory infections and the resultant antibiotic drug use was conducted among day care attendees in Israel. It was observed that children who had received the 9-valent conjugate vaccine showed a 17% overall reduction in antibiotic usage. In particular, a 10% reduction in days of antibiotic usage for upper respiratory tract infections, 47% fewer days of antibiotic usage for lower respiratory tract infections, and 20% fewer days of antibiotic usage for otitis media (ear infections) when compared to children who did not receive PCV.

Key Evidence: Several studies have shown a 13-50% reduction in the use of antibiotics by children who have received influenza vaccine compared with unvaccinated controls. This is due to a decline in febrile illnesses causes by influenza — for which antibiotics are often prescribed inappropriately — as well as a decline in secondary bacterial infections requiring antibiotic treatment, such as pneumonia and middle ear infections, that are triggered by influenza.

Key Evidence: In a study evaluating the impact of PCV7 on 40,000 recipients and control subjects in northern California revealed that the vaccine could significantly decrease the need for antibiotics to treat the disease. The children who had received the vaccine displayed a 5.4% reduction in the number of antibiotic prescriptions and a 12.6% reduction in the use of “second-line antibiotics” compared to the controls. Additionally, when looking at children in the time period between their first dose and attainment of the age of 3.5 years, receiving the vaccine had prevented 35 antibiotic prescriptions per 100 fully vaccinated children.

Key Evidence: In Iceland, a study of all children born over an 11-year period, before and after the introduction of pneumococcal conjugate vaccine (PCV) into the national immunization program, found a 6% decrease in all antibiotic prescriptions for children during their first four years of life and a 22% reduction in prescriptions for otitis media after the vaccine was introduced. Thus, in addition to reducing the burden of pneumococcal disease, PCV may also slow the spread of antibiotic resistance.

Key Evidence: A study led by researchers from the U.S. Centers for Disease Control and Prevention found that across five winter influenza seasons (2013-2018), vaccination against influenza averted 1 in 25 antibiotic prescriptions among outpatients with acute respiratory illness (ARI). The study population included 37,487 ARI outpatients 6 months or older treated at over 50 healthcare facilities across the United States. The authors conclude that influenza vaccination may curb unnecessary antibiotic use and help reduce the global threat of antibiotic resistance.

A retrospective analysis of influenza vaccination coverage and antibiotic prescribing rates from 2010 to 2017 across states in the United States, controlling for differences in health infrastructure and yearly vaccine effectiveness, found that a 10-percentage point increase in influenza vaccination coverage was associated with a 6.5% decrease in antibiotic use across all age groups, equivalent to 14.2 fewer antibiotic prescriptions per 1000 individuals.

Key Evidence: Vaccines against influenza reduce the use of antibiotics that drive drug resistance in bacteria in two ways. First, they prevent secondary bacterial infections caused by influenza, such as pneumonia and otitis media; in Ontario, Canada, the rate of prescribing for influenza-associated antibiotics declined around 64% after universal introduction of influenza vaccination compared to other Canadian provinces with more limited use of the vaccine. Second, they help prevent inappropriate antibiotic prescriptions for respiratory tract infections caused by influenza and other viruses, which account for half of all respiratory illnesses for which antibiotics are prescribed in the U.S.

Key Evidence: A community-based study in Vietnam found a high percent of children under five years of age were carrying pneumococcal bacteria in their noses and throats that were non-susceptible to commonly-used antibiotics. Of the strains tested, 18% were not susceptible to penicillin, 26% weren’t susceptible to cefotaxime, 76% were not susceptible to meropenem and 14% were not susceptible to all three nor to any of the “macrolide” drugs (e.g., erthromycin and azithromycin). However, 90% of the multi-drug resistant strains are serotypes that are in the 13-strain pneumococcal conjugate vaccine (PCV-13) and thus the introduction of a vaccine is expected to increase the susceptibility of circulating strains of the bacteria.

Key Evidence: The US CDC identifies the use of vaccines as one of the 4 critical steps for controlling the spread of antibiotic resistance.

Key Evidence: This systematic review suggests that vaccination against influenza and pneumococcus can reduce overall healthcare visits and antimicrobial consumption. Of the 26 studies included in the review, 23 found significant reductions in antimicrobial use in vaccinated individuals or groups. This evidence indicates that improved coverage with existing vaccines may significantly reduce antimicrobial demand.

Key Evidence: According to a study in a hypothetical endemic population, vaccination using typhoid conjugate vaccine will reverse the current increase in the percent of chronic carriers of the disease who are antibiotic resistant, if at least 50% of the target population is vaccinated. This would deplete an important “reservoir” of antibiotic resistant typhoid.

Key Evidence: A systematic review of studies from India found that prior to widespread use of the pneumococcal conjugate vaccine, antibiotic resistance in serious pneumoccocal infections among Indian children has been common. Penicillin resistance was found in 10% of invasive pneumococcal disease (IPD) cases, while trimethoprim/sulfamethoxazole resistance was found in more than 80% of these cases.

Key Evidence: Shortly after its introduction of Hib vaccine in the United Kingdom, a decrease in resistant (ᵝ-lactamase-positive) strains were documented. In the U.S., following introduction of pneumococcal conjugate vaccines, including PCV13, there was a decrease in both antibiotic use and in the prevalence of pneumococcal strains not susceptible to antibiotics.

Key Evidence: The US CDC estimates that antibiotic resistant pneumococcal infections in the US add $96 million to the costs of treatment each year.

Key Evidence: The costs and health effects of treating typhoid might soon increase dramatically, since the bacteria that causes typhoid is becoming increasingly resistant to the most effective oral antimicrobial drugs, thus requiring treatment with more expensive intravenous antibiotics which may result in more frequent hospitalizations for suspected typhoid cases.