Antimicrobial Resistance

Francisco Javier Álvarez

2022SE02

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 Antibiotic Resistance (2019)
• Each year in the United States, at least 2
million people become infected with bacteria
that are resistant to antibiotics and at least
23,000 people die each year as a direct result
of these infections.

Antibiotic Resistance
• Penicillin, the first commercialized antibiotic, was
discovered in 1928 by Alexander Fleming. While it
wasn’t distributed among the general public until
1945, it was widely used in World War II for surgical
and wound infections among the Allied Forces.
• It was hailed as a “miracle drug” and a future free
of infectious diseases was considered.
• When Fleming won the Nobel Prize for his
discovery, he warned of bacteria becoming resistant
to penicillin in his acceptance speech.

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 Antibiotic Resistance
• Up to 50% of the time antibiotics are not
optimally prescribed, often done so when not
needed, incorrect dosing or duration

• The germs that contaminate food can become

resistant because of the use of antibiotics in
people and in food animals.
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https://www.bbc.com/news/health-60058120

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 Antibiotic Resistance
• For some germs, like the bacteria Salmonella and
Campylobacter, it is primarily the use of antibiotics
in food animals that increases resistance.
• Because of the link the between antibiotic use in
food-producing animals and the occurrence of
antibiotic-resistant infections in humans, antibiotics
that are medically important to treating infections
in humans should be used in food-producing
animals only under veterinary oversight and only to
manage and treat infectious disease, not to
promote growth.

Questions
• Would you treat a cold, flu or most sore throats with
antibiotics?
• Should you keep leftover antibiotics at home in case you
need them in the future? (Why would you have leftover
antibiotics at home?)
• Should you stop taking antibiotics once you feel better?
• Do antibiotics target specifically the bad bacteria?

https://www.nytimes.com/2018/06/14/science/bacteria-harpoons-dna.html
 (What a surprise!)
• Data from a randomized controlled trial of children who had been diagnosed
with community-acquired pneumonia (CAP) and treated with beta-lactam
antibiotics.
• They found that a 5-day course of beta-lactam antibiotics was as effective as
the standard 10-day course in treating CAP.
• Shotgun sequencing of their metagenomes revealed fewer resistance genes in
children who had received the 5-day treatment regimen compared to those
who received the 10-day regimen.
• Surprisingly, the longer antibiotic course also led to a significant increase in
resistance genes associated with multiple other antibiotics.
• “The microbiome is so important for health, and disruption can lead to other
downstream effects, including susceptibility to other pathogens and antibiotic
resistance.”

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Study-Connects-Shorter-Course-of-Antibiotics-to-Fe

Is it healthier to use antimicrobial-containing products Is it healthier to use antimicrobial-containing products

(soaps, household cleaners) than regular products? (soaps, household cleaners) than regular products?

• To date, studies have shown that there is no added health benefit for

consumers (this does not include professionals in the healthcare setting)

using soaps containing antibacterial ingredients compared with using plain

soap.

• This proposed rule does not affect hand sanitizers, wipes, or antibacterial

products used in healthcare settings.

 Can antibiotic resistance develop Can antibiotic resistance develop
from using acne medication? from using acne medication?

Yes. Antibiotic use, appropriate or not, contributes to the development of

antibiotic resistance. This is true for acne medications that contain antibiotics.

Short- and long-term use of antibiotics for treatment or prevention of bacterial

infections should be under the direction of a healthcare professional to ensure

appropriate use and detection of resistance.

Can antibiotic treatment cause side effects? Can antibiotic treatment cause side effects?

Yes. Reactions from antibiotics cause one out of six visits

to the emergency department. In children younger than six,
reactions to antibiotics are the most common reason for
medication-related emergency department visits.
 https://www.upi.com/Health_News/2022/05/26/inappropriately-
prescribed-anitbiotics-children-cost-74-million-study/4411653576949/

Otras enfermedades que están resurgiendo

La peste negra mató a • Tuberculosis

50 millones en Europa
(60% del total) • Gonorrea
• Sífilis
En todo el mundo, mató
a 100 millones
• Cólera
• Lyme disease
• MRSA
 Microbiota intestinal
• Aunque algunas bacterias atacan al cuerpo humano, la
mayoría de aquellas con las que compartimos nuestro
cuerpo son inocuas e incluso beneficiosas

• Por ejemplo, la comunidad bacteriana normal de la vagina

femenina crea un ambiente hostil a las infecciones por
parásitos como las levaduras

• A las bacterias beneficiosas de nuestra microbiota intestinal

también les afectan los antibióticos
 https://phys.org/news/2022-01-gene-georgia-global-threat.html

• A gene that causes bacteria to be resistant to one of the world's most

important antibiotics, colistin, has been detected in sewer water in
Georgia. The presence of the MCR-9 gene is a major concern for public
health because it causes antimicrobial resistance, a problem that the World
Health Organization has declared "one of the top 10 global public health • It was previously believed that agriculture was a driving factor in the spread
threats facing humanity.” of MCR. Nations such as China and India use the colistin antibiotic in
livestock.
• Colistin is considered a "last resort" antibiotic because it can kill infections
• Researchers from the University of Georgia's Center for Food Safety (CFS) that other antibiotics cannot. Its frequent use means that some bacteria
collected sewage water from an urban setting in Georgia to test for the are becoming resistant to it.
MCR gene in naturally present bacteria. The team was surprised at how
quickly they detected MCR—they found evidence of the gene in the first • This means that if people or animals contract a strain of colistin-resistant
sample they took. bacteria, there are potentially no medications that can treat their infection.
• They face extreme, invasive health measures and possible death.

• The bacteria where the gene was found, Morganella morganii, is not often
tested by researchers. This means that the problem could be considerably
more widespread than initially thought.
https://phys.org/news/2022-01-gene-georgia-global-threat.html https://phys.org/news/2022-01-gene-georgia-global-threat.html
 https://www.eldiario.es/sociedad/muertes-anuales-bacterias-resistentes-
medicamentos-superan-causadas-sida-malaria_1_8670535.html

El nuevo informe de Global Research on Antimicrobial

Resistance (GRAM) hace una estimación de las muertes
relacionadas con 23 patógenos y 88 combinaciones
Chris Murray, del Institute for Health Metrics and
patógeno-fármaco en 204 países y territorios en el año 2019.
Evaluation de la Universidad de Washington: Para ello, se han utilizado modelos estadísticos para producir
“Las estimaciones anteriores preveían 10 estimaciones del impacto de la RAM en todos los lugares –
millones de muertes anuales por RAM para también en los lugares para los que no tienen datos–.
2050, pero ahora sabemos con certeza que ya Por un lado, la investigación calcula que la resistencia a ese
tipo de medicamentos ha causado directamente 1,27
estamos mucho más cerca de esa cifra de lo millones de muertes durante el transcurso de 2019; por otro,
que pensábamos" indica también que las infecciones resistentes tuvieron algún
tipo de papel en 4,95 millones de muertes.
MRSA
• “Gonorrhoea is a very smart bug,” said Teodora Wi, a
human reproduction specialist at the Geneva-based UN
health agency. “Every time you introduce a new type of
antibiotic to treat it, this bug develops resistance to it.”

• The WHO estimates 78 million people a year get

gonorrhoea, an STD that can infect the genitals, rectum
and throat.

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https://resistancebank.org/

More AMR in countries with more antibiotics use,

even in people who don’t take antibiotics
• “Even people without recent antibiotic use have higher
antibiotic-resistant strains of pathogens in countries with
high antibiotic use than healthy people in countries with
…In 2019, 4.95 million deaths comparatively lower antibiotic use.”
were associated with drug-resistant
bacterial infections, of which 1.27
million deaths were directly caused
by antimicrobial resistance – a huge • "Even a healthy individual, who hasn't taken antibiotics
burden in all areas of the world, but
particularly impacting low- and
recently, is constantly bombarded by microbes from
middle-income countries. people or pets they interact with that can lead to
Summary: https://www.sciencealert.com/the-
resistance genes becoming embedded in their own
third-leading-cause-of-death-globally-in-2019- microbiota.”
was-antibiotic-resistant-bacterial-infection
https://www.sciencealert.com/antibiotic-resistance-
can-emerge-in-your-gut-even-without-antibiotics-use
 Antibiotics and animal farming
Fact: 70% of antibiotics are given to farm animals

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farmaceuticas_6_628247185.html

• ¿Por qué las grandes farmacéuticas no quieren invertir en

investigación para desarrollar nuevos antibióticos?

• ¿Hay algo que puedan hacer los doctores y los pacientes?

 Cindy M. Liu et al, Escherichia coli ST131-H22 as a Foodborne
Uropathogen, mBio (2018). DOI: 10.1128/mBio.00470-18

“This study showed a clonal link between E.

coli from meat and humans, providing solid
evidence that UTI is zoonosis. The close
relationship between community-dwelling
human and UTI isolates may indicate a point https://medicalxpress.com/news/2018-08-
coli-strain-retail-poultry-urinary.html
source spread, e.g. through contaminated
meat.”

https://medicalxpress.com/news/2023-03-
bacteria-meat-half-million-urinary-tract.html

slurry pits
(pozos negros)

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industrial-anade-riesgo-salud-humana-contaminar-rios.html
 Antifungal Resistance

2. Mechanisms of
fungal resistance
(Example of Candida albicans)

C. albicans is the most common human

• Fungi can colonize almost any human niche fungal pathogen
➢Reprogramming events for adaptation
➢Fight for nutrient acquisition • Healthy Individuals: Commensal organism

➢Deal with host defence mechanisms • Mucosal Infections: Thrush, etc.

• Some fungi are commensal: fungi have been
• Systemic Infections: Life threatening
with humans for millions of years (ex. Candida (38% mortality)
albicans, Malassezia spp.)
• Host: Resistance vs. Tolerance Susceptibility Factors:
Immunocompromised Neutropenic
Cancer therapy Organ transplantation
Antibiotic therapy Medical devices
 Candida albicans is an opportunistic
human fungal pathogen Antifungal Resistance
• The fungus Candida is the most common cause
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of healthcare-associated bloodstream
infections in the United States
• Each case of Candida bloodstream infection
(also known as candidemia) is estimated to
result in an additional 3 to 13 days of
hospitalization and $6,000 to $29,000 in
healthcare costs

Fungal Virulence Factors

Virulence factors: cause cell or tissue damage
– Adhesion factors: fimbriae, spikes, capsules
– Secretion of lytic enzymes, toxins, etc.
Septic shock. Aspergillus -> aflatoxins;
Claviceps -> ergotism. Bioagents
– Ability to form biofilms
– Ability to switch growth from budding to
hyphal cells
https://slideplayer.com/slide/774256/
 Caspofungin
Structures of representative antifungal agents
Amphotericin B

Ghannoum M A , and Rice L B Clin. Microbiol. Rev.

Fluconazole 1999;12:501-517

1950s
Bad for the kidneys 2001

Mostly for
external infections

1980s

Mostly in
combination
with other drugs
 Antifungal Resistance Mechanisms of fluconazole resistance

• CDC’s surveillance data indicate that the • Mutations in ERG11

proportion of Candida isolates that are • Overexpression of ERG11
resistant to fluconazole has remained fairly • Overexpression of genes for efflux pumps
constant over the past twenty years
• Echinocandin resistance, however, appears to
be on the rise, especially among Candida
glabrata: from 4% in 2008 to 8% in 2014

Why we don’t see an increase in resistance to

fluconazole worldwide?
• Only 2-5% of clinical isolates are resistant to
fluconazole
• It hasn’t increased in decades: it’s a rare event
• In most cases strains are homozygous for the
mutation => LOH (Loss of Heterozygosity,
which affects linked genes) by genomic
rearrangements
• Loss of fitness associated to those mutations
 Fitness Antifungal Resistance
• Competition experiments: wild type red • For multi-drug resistant Candida infections
fluorescence vs. mutant strains (those that are resistant to both fluconazole
• In the presence of fluconazole, mutant strains and an echinocandin), the few remaining
survive better treatment options are expensive and can be
• Homozygous mutant strains survive better toxic for patients who are already very sick
than heterozygous strains
• However, in the absence of antifungals the
wild type has better fitness than the mutants

Genetic conditions can increase susceptibility

Antifungal Resistance to fungal infections

• Resistance over time as a result of improper • Invasive aspergillosis: mutations in genes

antifungal use—for example, dosages that are too CXCL10, DECTIN1, IL1RN, IL10, IL23R, MASP2,
low or treatment courses that aren’t long enough MBL2, PLG, TLR1, TLR4, TLR6, TNFR1, TNFR2
• Antibacterial medications may also contribute to
• Chronic monocutaneous candidiasis: CARD9,
antifungal resistance; this could occur for a variety
DECTIN1
of reasons, one of which is that antibacterials
reduce bacteria in the gut and create favorable • Vulvovaginal candidiasis: IL4, MBL2, NLRP3
conditions for Candida growth
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 https://asm.org/Press-Releases/2022/March-2022/
Apples-and-Other-Fruits-Can-Host-Drug-Resistant,-P

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person-to-person-transmission-of-resistant-fungus-69019

Antifungal Resistance
• The global prevalence of azole resistance in
Aspergillus is estimated to be approximately 3
to 6 percent
Some good news too
• Some studies suggest that resistance in
Aspergillus may be partially driven by the use
of agricultural azoles, which protect crops from
fungi
 Zhang et al., Science 370, 974–978 (2020)

Ernst Haeckel Interpretación

https://www.elespanol.com/ciencia/investigacion/20180323/secreto- de varias ascidias (sea squirts).
De Kunstformen der Natur
leche-ornitorrinco-puede-salvar-millones-vidas/292471110_0.html (Artforms of Nature), 1904.
FIG. 1. Isolation chip, or ichip, for high-throughput microbial cultivation in situ. (A) Dipping a plate with multiple through-holes into a suspension
of mixed environmental cells leads to capturing (on average) a single cell (B). (C) Ichip assembly: membranes cover arrays of through-holes from
each side; upper and bottom plates with matching holes press the membranes against the central (loaded) plate. Screws provide sufficient pressure
to seal the content of individual through-holes, each becoming a miniature diffusion chamber containing (on average) a single cell. (Artwork by
https://www.sciencedaily.com/releases/2022/05/220526141531.htm
Stacie Bumgarner, Whitehead Institute for Biomedical Sciences, Cambridge, MA.)
 A new pool of antibiotics
• “Frustrated with their inability to unlock many bacterial gene clusters,
Brady and colleagues turned to algorithms. By teasing apart the
genetic instructions within a DNA sequence, modern algorithms can Nuño Domínguez. 03 may 2022
predict the structure of the antibiotic like compounds that a
bacterium with these sequences would produce. Organic chemists can
then take that data and synthesize the predicted structure in the lab.”

• “It may not always be a perfect prediction. "The molecule that we end
up with is presumably, but not necessarily, what those genes would
produce in nature. We aren't concerned if it is not exactly right - we
only need the synthetic molecule to be close enough that it acts
similarly to the compound that evolved in nature." https://elpais.com/ciencia/2022-05-03/un-
virus-salva-a-un-hombre-de-una-bacteria-
https://www.sciencedaily.com/releases/2022/05/220526141531.htm resistente-a-todos-los-antibioticos.html
 Cocineros/as de Alto Riesgo

Perfumes
Degustación
Saliva
Cocineros/as de Alto Riesgo Colgantes
Tabaco
Lavado de manos

Limpieza de lentes

Uniforme

Cinco pasos para evitar enfermedades transmitidas por alimentos

Manipuladores de alimentos
¿Cómo eliminar estas bacterias? La forma más eficaz de hacerlo es cocinar bien la carne
de las aves, “que no debe consumirse nunca cruda”. Pero además, para evitar esta
• Vestimenta. Color, bolsillos, botones, joyas, perfumes. toxiinfección alimentaria y otras contaminaciones, se recomiendan cinco claves para la
seguridad de los alimentos:
• Partes del cuerpo. Manos, uñas, piel, cabello, ojos, nariz, boca.
• Mantener la limpieza: Lavar siempre las manos antes de preparar alimentos y
• Cuándo lavarse las manos. también varias veces durante la preparación y utilizar un papel desechable para su
secado. También deben limpiarse todas las superficies y los utensilios y trapos
• De lo crudo a lo cocinado. utilizados. Además, es esencial guardar los alimentos en recipientes cerrados y
• Heridas, rasguños, granos, abscesos. Cómo cubrir las heridas. protegerlos de insectos y mascotas.

• Hábitos. Tocamientos. Tabaco. • Separar alimentos crudos y cocinados: No se deben utilizar los mismos cuchillos
o tablas de cortar, para manipular alimentos crudos, como pescado, carne o pollo, y
• En caso de enfermedad del manipulador para alimentos ya cocinados. “Se recomienda usar una tabla de cortar para los
alimentos que vamos a consumir crudos y otra para los alimentos que vamos a
cocinar, porque las bacterias de los mismos son distintas y no se deben mezclar”,
dice Gonzalo. Los alimentos crudos y cocinados deben conservarse en recipientes
separados.
Cinco pasos para evitar enfermedades transmitidas por alimentos

• Los alimentos deben cocinarse completamente, especialmente la carne, el pollo,

los huevos y el pescado. Además se debe asegurar que los guisos y sopas alcancen
el punto de ebullición y que el recalentado de las comidas se lleva a cabo
correctamente.

• Mantenga los alimentos a temperaturas seguras. No deje los alimentos

cocinados a temperatura ambiente. Almacene en refrigeración lo más pronto
posible los alimentos cocinados y los perecederos, preferiblemente por debajo de
5° C. La comida cocinada que va a ser consumida caliente debe mantenerse por
encima de los 60ºC. Además, a la hora de descongelar un alimento, hágalo en la
parte baja del frigorífico.

• Use agua potable y alimentos seguros: Seleccione alimentos saludables y frescos.

No consuma leche que no haya sido pasteurizada o esterilizada. Lave las frutas
y las hortalizas, especialmente si se comen crudas y no consuma alimentos después
de su fecha de caducidad. https://cuidateplus.marca.com/alimentacion/nutricion/
2020/09/30/motivos-deberias-lavar-pollo-cocinarlo-175065.html

Campylobacter Síntomas más frecuentes

• Diarrea (frecuentemente
• “Lavar el pollo antes de cocinarlo aumenta el riesgo de sanguinolenta)
propagación de la bacteria Campylobacter en las manos,
• Dolor abdominal
las superficies de trabajo, la ropa y los utensilios de cocina a
• Fiebre
través de la salpicadura de gotas de agua”
• Dolor de cabeza
• Campylobacter es causante de la toxiinfección alimentaria
• Náuseas y/o vómitos
más frecuente en Europa
• Los síntomas graves pueden ser
• Es también una de las cuatro principales causas mundiales más frecuentes en personas
de enfermedad diarreica y está considerada como la causa mayores, embarazadas, niños o
bacteriana más frecuente de gastroenteritis en el mundo pacientes inmunodeprimidos
 Cinco pasos para evitar enfermedades transmitidas por alimentos
Tampoco hay que lavar los huevos
¿Cómo eliminar estas bacterias? La forma más eficaz de hacerlo es cocinar bien la carne
de las aves, “que no debe consumirse nunca cruda”. Pero además, para evitar esta
toxiinfección alimentaria y otras contaminaciones, se recomiendan cinco claves para la
seguridad de los alimentos:
• Mantener la limpieza: manos, superficies, utensilios y trapos utilizados. Guardar los Los CDC tampoco aconsejan el lavado de los
alimentos en recipientes cerrados. huevos. La cáscara de los huevos es porosa,
por lo que al lavarlos se facilita la entrada en
• Separar alimentos crudos y cocinados y los utensilios utilizados para su su interior de patógenos.
manipulación. “Los huevos se deben limpiar con papel de
cocina y romper la cáscara de cada uno por
• Los alimentos deben cocinarse completamente. separado teniendo cuidado de que la misma no
entre en contacto con la clara y la yema”.
• Mantenga los alimentos a temperaturas seguras.
No se deben lavar y guardar, si acaso lavarlos
• Use agua potable y alimentos seguros. justo antes de cocinarlos.

• No consuma leche que no haya sido pasteurizada o esterilizada.

https://elpais.com/ciencia/2022-04-08/donde-se-acumulan-los-microbios-en-mi-cocina.html
https://elpais.com/ciencia/2022-04-08/donde-se-acumulan-los-microbios-en-mi-cocina.html

Our body knows tells us

not to eat bad stuff
 ¿Deberíamos cambiar
nuestras costumbres?

https://youtu.be/HaJQq4K-byw