Carrera de

Medicina Humana
Farmacología General y Especial

2023-2
Antibacterianos
Dr. Jorge S. Salas Pereda

Semanas 13 y 14
 Resultado de Aprendizaje de la Sesión

Al finalizar la sesión, el estudiante selecciona qué

fármacos indicar para tratar las enfermedades
infectocontagiosas más frecuentes, con agentes
que tengan un óptimo perfil farmacocinético,
farmacodinámico, de eficacia y de seguridad.
 Reflexión desde la Experiencia
♂4a. sufre excoriación en rodilla D mientras jugaba fulbito. Al otro día
presenta T 38.2°C, dolor y flogosis perilesional de extensión creciente.
♂68a., c/tos, flema herrumbrosa, disnea, dolor en HTD x 2d. Físico: PA
97/58mmHg, P 102, R 32, T 39°C, Sat.O2 96%, matidez, soplo tubárico,
crépitos inspiratorios en 1/3 medio de HTD. Ex. Aux.: Le 12800/mm3, Ab
8%, BUN 22mg/dL. Rx. Tórax: Radioopacidad en LMD.
♀24a. gestante 11ss, con disuria y polaquiuria. PPL(-). ECO: Leu 18xC.
♀3a. c/diarrea x 1 día, ↓volumen, c/moco, rasgos de sangre y tenesmo.
Ex. Físico: T 38.5°C, hidratada, irritable, ↑RHA, dolor leve a palpación.
¿Cuá sería su conducta terapéutica en cada caso?
Definiciones
✓ Antibiótico: Sustancia secretada por un organismo vivo,
generalmente un microorganismo, que inhibe la
replicación, el crecimiento o elimina a otros
microorganismos y células anormales de animales
superiores.
✓ Quimioterápico: Sustancia química sintética obtenida
para tratar infecciones al erradicar los microorganismos
infectantes sin lesionar los tejidos del huésped.
→ Definiciones
GRADO DE ACCIÓN:
✓ Bacteriostático: Inhibición reversible y temporal de
quimioterápicos o antibióticos, lo que atenúa el
crecimiento o proliferación de agentes microbianos y
facilita su erradicación por el sistema inmunológico.
✓ Bactericida: Quimioterápico o antibiótico que causa
la muerte de los microorganismos infectantes.
→ Definiciones
ESPECTRO DE ACCIÓN:
➢Muy estrecho: Activo contra ciertos microorganismos.
➢Estrecho: Activo contra uno o pocos grupos de m.o.
➢Amplio: Activo contra m.o. Gram (+) y ↑N° de Gram (-),
anaerobios, atípicos, micobacerias y m.o. intracelulares.
➢Extendido: Activo contra numerosos y diversos grupos
de microorganismos incluyendo aquellos resistentes.
Historia
de la
ABT

Current Opinion in
Microbiology 2019,
51:72–80.
 Origen de los ABT

Current Opinion in Microbiology 2019, 51:72–80.

Origen
de los
ABT

Current Opinion
in Microbiology
2019, 51:72–80.
Origen
de los
ABT

Current Opinion
in Microbiology
2019, 51:72–80.
Origen
de los
ABT

Current Opinion
in Microbiology
2019, 51:72–80.
 Características de un ABT ideal
✓ Mínima generación de resistencia ✓ Disponible por VO y resistente al HCl
✓ Mínimas RAM (incluyendo teratogénesis) ✓ Hidrosolubles y estables en plasma, líquidos
orgánicos o exudados.
✓ Alta actividad biológica y de amplio espectro
✓ Acumulación en macrófagos y distribución a tejidos
✓ Toxicidad selectiva (activo contra m.o. e inocuo para

no existe
difíciles de alcanzar (SNC, hueso, abscesos, etc.)
las células del huésped [modelo prodroga →
activada por m.o.]) ✓ No interacciones farmacológicas (BT y UPP) y
excreción sin cambios.
✓ Alto índice terapéutico (DT50/DE50)
✓ No causar hemólisis o afectar a los fagocitos
✓ Alta especificidad (activo contra patógenos, no
contra la microbiota) ✓ Activo contra m.o. persistentes y en biofilm
✓ No causar reacciones de hipersensibilidad, ✓ Concentración MIC a nivel nanomolar
histaminoide, o de pirógeno.
✓ Múltiples target bacterianos y mecanismos de acción
✓ Alta solubilidad y permeabilidad (BCS class I)
✓ Unión covalente (irreversible) a blancos bacterianos.
The concept of an ideal antibiotic: implications for drug design. Molecules. 2019 Mar; 24(5): 892.
Mecanismos de
Acción
y
Mecanismos de
Resistencia

Lancet Infect Dis. 2020

Sep;20(9):e216-e230.
 Alteration of Cell
Membrane Replication
Polymyxins
Bacitracin
Neomycin

Transcription

PABA →→ THF
Mecanismos
de Acción
Translation

Translation
Inhibición de la Síntesis de Proteínas
 Disrupción de
la Membrana
Celular

Inhibición de la
Síntesis de
Metabolitos
Esenciales
•. 2020 Sep;20(9):e216-e230.

Mecanismos de
Acción de los
Péptidos
Antimicrobianos

Lancet Infect Dis. 2020

Sep;20(9):e216-e230.
Mecanismos Resistencia
Ejemplo de resistencia a antibióticos

Streptococcus pyogenes 17 % a macrolidos

Steptococcus neumoniae 40 % penicilinas
18 % Macrolidos
Haemophilus influenzae 40 % Amino penicilinas
40 % Fluoroquinolonas
Neisseria meningitidis 30 % Penicilinas
Salmonella typhimurium 25 % Ampicilina
Campylobacter jejunis 50 % Fluoroquinolonas
Escherichiae coli 60 % Aminopenicilinas
15 % Asociación Inhib. betalactamasas
10 % Fluoroquinolonas
 1 1+

Terapia
Monoterapia
Combinada

Alternativa a la monoterapia para

Opción de tratamiento habitual de
infecciones que no responden al
una infección bacteriana invasiva
tratamiento estándar
Potential synergistic combinations determined by checkerboard
and time-kill assays showing cefoxitin as an active partner
 Problemática del Uso de Antibióticos
❑Insuficiente información etiológica en la
práctica diaria
❑Espectro cambiante
❑Uso irracional
❑Creciente aparición de resistencia
❑Perspectivas actuales y futuras de la
antibioterapia
 Qué debemos conocer para indicar un
antibiótico
❑Estructura química
❑Mecanismo de acción
❑Actividad antibacteriana
❑Farmacocinética
❑Reacciones adversas
❑Resistencia bacteriana
❑Uso clínico
Antibióticos
Criterios de elección
❑Etiología
❑Sensibilidad
❑Espectro
❑Eficacia
❑Tolerancia
❑Costo
❑Vía de administración
ATÍPICOS
 AmpC

CEFAMICINAS
Farmoquímica de los
Antibacterianos
Clasificación de los
Antibacterianos
 Comparación de la Actividad de las
Cefalosporinas.
ACTIVIDAD
GENERACIÓN
Gram (+) Gram (-)

1° +++ +/-

2° ++ +

3° + +++
+++
4° ++
P. aeruginosa
++
5° +++
MRSA
Clasificación de los
Antibacterianos
Nuevos Antibacterianos – FDA 2017-2020

Curr Emerg Hosp Med

Rep 2020 Jun;16:1–6.
 Nuevos Antibacterianos – FDA 2017-2020

Nuevas
Indicaciones

Curr Emerg Hosp Med

Rep 2020 Jun;16:1–6.
Nuevos antibacterianos en desarrollo

Curr Emerg Hosp Med

Rep 2020 Jun;16:1–6.
 Péptidos
Antimicrobianos
en desarrollo

Lancet Infect Dis. 2020

Sep;20(9):e216-e230.
 Péptidos
Antimicrobianos
en desarrollo

Lancet Infect Dis. 2020

Sep;20(9):e216-e230.
Características de los
Antibacterianos
Características de los
Antibacterianos
 Sinusitis Aguda GUÍA DE TERAPIA ANTIMICROBIANA: NIÑOS DE 1 MES A 1 AÑO
No ABT en mayoría de casos, resuelve en 14 d. Si sg. Alarma: Bacterial Conjunctivitis
First line: Phenoxymethylpencilin 62.5mg QDS Most are viral & self-limiting – Treat if severe First Line: Chloramphenicol
Penicillin allergy: Doxycyline or clarithryomycin
0.5% eye drops Initially 1 drop ev 2 hours for 2 days, then reduce OR
Sore Throat (Acute) Chloramphenicol 1% eye ointment TDS- QDS Alternative: Fusidic acid
Avoid antibiotics as 82% resolve in 7 days without. Pain 1% gel apply BD Continue for 48 hours after healing
only reduced by 16 hours. Assess severity using Fever PAIN Acute Otitis Media
First line: Phenoxymethylpenicillin
62.5mg QDS for 5-10 days
60% are better within 24 hours without antibiotics
Penicillin allergy: Clarithromycin First line: Amoxicillin 125mg TDS for 5 days
Dose based on weight (see BNF-C) for 5 days Penicillin allergy: Erythromycin
125mg QDS for 5 days
Pneumonia (Community acquired) Impetigo
If CRB65=0, First Line: Amoxicillin Reserve topical antibiotics (fusidic acid thinly TDS 5/7) for very
125mg TDS for 5 days* localised lesions to reduce risk of bacteria becoming resistant. Only
Penicillin allergy: Clarithromycin Dose dependent on body weight (see use mupirocin if caused by MRSA.
BNF-C) for 5 days*
*Review at 3 days. Extend to 7-10 days if poor response
First Line: Flucloxacillin 7/7
If CRB65=1-2 & managed at home Amoxicillin AND Clarithromycin for PNC Allergy: Clarithromycin Dose based on weight
7-10 days. Urinary Tract infections
If CRB 3-4 Urgent hospital admission <3 months - urgently refer
Cellulitis and Wound Infection First line: Flucloxacillin 62.5- >3 months: use positive nitrite to guide antibiotic use
125mg QDS for 7 days Lower UTI - First Line: Cefalexin 125mg BD for 3 days
Penicillin Allergy: Clarithromycin Upper UTI - refer to paediatrics
Dose based on weight (see BNF-C) for 7 days
Threadworms
All household contacts should be treated at the same time Human/ animal bites First Line: Co-amoxiclav
<6 months good hygiene measures 0.25 ml/kg of 125/31 susp TDS for 7 days
>6 months of age: Mebendazole 100mg single dose (a second dose Penicillin allergy in human bites: Metronidazole PLUS Clarithromycin
may be needed after 2 weeks)(unlicensed but is an accepted treatment, Penicillin allergy in animal bites: metronidazole PLUS doxycycline
endorsed by BNF-C)
Note: If meningitis is suspected General Practitioners are advised to give a single IV dose of benzylpenicillin, prior to urgently transporting the patient to hospital
<1 year 300mg; 1-9 years 600mg; 10 years and over 1.2g (same as adults). Alternative: Cefotaxime <12 years 50mg/kg; 12 years and over 1g. Give IM if vein cannot be found.

Based on North East and Cumbria Primary Care Antibiotic Prescribing Guidelines version April 2018 Review April 2020
 GUÍA DE TERAPIA ANTIMICROBIANA: NIÑOS DE 1 A 12 AÑOS
Acute sinusitis
Do not offer antibiotics as most resolve in 14 days without
First line:1-5yrs Phenoxymethylpenicillin 125mg QDS 5/7 Bacterial Conjunctivitis
6-11yrs Phenoxymethylpenicillin 250mg QDS 5/7 Most are viral & self-limiting - Treat if severe First line: Chloramphenicol 0.5% eye
12 yrs Phenoxymethylpenicillin 500mg QDS 5/7 drops Initially 1 drop ev 2 hours for 2 days, then reduce OR Chloramphenicol 1%
Penicillin allergy: Doxycyline or clarithryomycin see BNFc for doses eye ointment TDS-QDS Alternative: Fusidic acid 1% gel apply BD Continue for 48
Sore Throat (Acute) hours after healing
Avoid antibiotics as 82% resolve in 7 days without. Assess severity using FeverPAIN Acute Otitis Media
First line: Phenoxymethylpenicillin 60% are better within 24 hours without antibiotics
1-6 years 125mg QDS for 5-10 days 6-11 years 250mg QDS for 5-10 days First line: Amoxicillin
12 years 500mg QDS for 5-10days 1-4 years: 250mg TDS for 5 days 5-12 years: 500mg TDS for 5 days
Penicillin allergy: Clarithromycin Penicillin allergy: Erythromycin <2 years: 125mg QDS for 5 days
Dose based on wgt (see BNF-C) 5 days 2-7 years: 250mg QDS for 5 days
Pneumonia (Community acquired) >8 years: 250–500mg QDS for 5 days
If CRB65=0 First Line: Amoxicillin
1-4 years 250mg TDS for 5* days Impetigo
5-12 years 500mg TDS for 5* days *Review at 3 days. Extend to 7-10 days if poor response Reserve topical antibiotics (fusidic acid thinly TDS 5/7) for very localised lesions to
Penicillin allergy: Clarithromycin reduce risk of bacteria becoming resistant. Only use mupirocin if caused by MRSA.
Dose based on wgt (see BNF-C) 7 days First Line: Flucloxacillin 7/7
If CRB65=1-2 & managed at home Amoxicillin PLUS Clarithromycin for 7-10 days. Penicillin Allergy: Clarithromycin Dose based on weight (see BNF-C) for 7 days
If CRB 3-4 Urgent hospital admission
Urinary Tract infections
Cellulitis and Wound Infection
If unwell - use positive nitrite to guide Lower UTI – First Line: Cefalexin
First Line: Flucloxacillin
1–4 years: 125 mg TDS for 3 days
2-9 years: 125–250 mg QDS for 7 days
5–11 years: 250mg TDS for 3 days 12yrs: 500mg BD-TDS
10-12 years: 250–500 mg QDS for 7 days Penicillin Allergy: Clarithromycin
Upper UTI -refer to paediatrics
Dose based on weight (see BNF-C) 7 days
Threadworm
Human/ animal bites First Line: Co-amoxiclav
All household contacts should be treated at the same time. Mebendazole
1-5 years: (125/31 susp) 0.25ml/kgTDS for 7 days
100mg single dose (a second dose may be needed after 2
6-11 years: (250/62 susp) - 5ml TDS for 7 days
weeks)(unlicensed if under 2 yrs, endorsed by BNF-C) Available OTC
Penicillin allergy in human bites: Metronidazole PLUS Clarithromycin
Penicillin allergy in animal bites: metronidazole PLUS doxycycline

Note: If meningitis is suspected General Practitioners are advised to give a single IV dose of benzylpenicillin, prior to urgently transporting the patient to hospital
<1 year 300mg; 1-9 years 600mg; 10 years and over 1.2g (same as adults). Alternative: Cefotaxime <12 years 50mg/kg; 12 years and over 1g. Give IM if vein cannot be found.

Based on North East and Cumbria Primary Care Antibiotic Prescribing Guidelines version April 2018 Review April 2020
 Otitis Externa
First line: analgesia for pain relief, and apply localised heat (eg a warm flannel)
Second line: topical acetic acid 2% 1 spray TDS for 7 days or topical neomycin
sulphate with corticosteroid 3 drop s TDS
Acute Otitis Media Bacterial Conjunctivitis
Avoid antibiotics as 60% are better within 24 hrs without treatment. Only treat if severe, most are viral or self limiting
First line: Amoxicillin for 5 days. If penicillin allergy: Erythromycin or First line: Chloramphenicol 0.5% drops 1drop every 2hr for 2 days then reduce frequency . Or
Clarithromycin Chloramphenicol 1% eye ointment 3-4 times daily or just at night if using drops
Alternative: Fusidic acid 1% gel apply BD Continue all treatments for 48 hours after healing.
Acute sinusitis Impetigo
Symptoms <10days Do not offer antibiotics as most resolve in 14 days – consider Reserve topical antibiotics (fusidic acid thinly TDS 5/7) for very localised lesions to
delayed. Symptoms > 10days no antibiotic or consider back up antibiotic reduce risk of bacteria becoming resistant. Only use mupirocin if caused by MRSA.
Rx First line: Phenoxymethylpenicillin 500mg QDS 5/7 Extensive, severe, or bullous: oral antibiotics (Flucloxacillin 250-500mg QDS 7/7 OR
Penicillin allergy: Doxycycline 200mg stat then 100mg OD or Clarithromycin clarithromycin 250-500mg BD 7/7)
500mg BD for 5/7 Community Acquired Pneumonia
Very unwell or worsening: Co-amoxiclav 625mg TDS 5/7 Use CRB-65 score as a guide to treatment
If CRB-65=0 First line: Amoxicillin 500mg TDS for 5 days*
Acute sore throat
Penicillin allergy: Clarithromycin 500mg BD for 5 days* Or: Doxycycline 200mg stat,
Avoid antibiotics as 82% of cases resolve in 7 days, and pain is only reduced by 16 hours.
then 100mg OD for 5 days*
Assess severity using FeverPAIN score
*Review at 3 days, extend to 7-10 days if poor response
First line: Phenoxymethylpenicillin 500mg QDS (severe) or 1g BD (less severe) for 5-10 days
If CRB-65=1-2 and able to be managed at home
Penicillin allergy: Clarithromycin 250-500mg BD for 5 days
First line: Amoxicillin 500mg TDS for 7-10 days PLUS Clarithromycin 500mg BD for
7-10 days Or: Doxycycline 200mg stat, then 100mg OD for 7-10 days
Exacerbation of COPD IF CRB 3-4 Urgent hospital admission
Treat with antibiotics if purulent sputum and increased shortness of breath UTI in men and non-pregnant women
and/or increased sputum volume. First line: Nitrofurantoin 100mg BD (modified release) or 50mg QDS (standard release)
Amoxicillin 500mg TDS for 5 days OR for 3 days in women & 7 days in men (contra-indicated in patients with eGFR<45ml/min)
Doxycycline 200mg stat then 100mg OD for 5 days or Alternative If low risk of resistance: Trimethoprim 200mg BD for 3 days in women/ 7
Clarithromycin 500mg BD 5/7 days in men
Alternative (if resistance risk factors) Co-amoxiclav 625mg TDS for 5 days If first line unsuitable: Pivmecillinam 400mg stat then 200mg TDS 3 days in women/7
Acute cough & bronchitis days in men
Antibiotics of little benefit if no co-morbidity. Second line, consider 7 day delayed If susceptible: amoxicillin 500mg TDS 3 days for women/7days in men
antibiotic with advice. If high resistance risk: fosfomycin 3g stat. Men: a further 3g on day 3
Consider immediate antibiotics if >80years and one of: hospitalisation in the past year,
oral steroids, insulin-dependent diabetic, congestive heart failure, serious neurological Bacterial Vaginosis
disorder/stroke OR >65 years with two of the above. First line: Metronidazole PO 400mg BD for 7 days
Consider CRP if antibiotic is being considered. No antibiotics if CRP<20mg/L and Or Metronidazole PO 2g stat (2g stat dose should not be used in pregnant women)
symptoms for >24 hours; delayed antibiotics if 20-100mg/L; immediate antibiotics if Alternative: Metronidazole vaginal gel 0.75% 5g intravaginally at night for 5 nights
>100mg/L. Or Clindamycin cream 2% 5g intravaginally at night for 7 nights
First line: Amoxicillin 500mg TDS for 5 days OR Doxycycline 200mg stat then
100mg OD for 5 days Vaginal candidiasis
Clotrimazole pessary 500mg stat Or Clotrimazole vaginal cream 10% stat Or
Acute Prostatitis Fluconazole PO 150mg stat Or Miconazole 100mg pessary 14 nights
Send MSU for culture and start antibiotics. First line: Ciprofloxacin 500mg BD or Recurrent: Fluconazole PO 150mg every 72 hours 3 doses then 150mg weekly for 6/12
Ofloxacin 200mg BD for 28 days. Second line: Trimethoprim 200mg BD for 28 days
Cellulitis and Wound Infection
Human/ Animal bites
Diarrhoeal Illness First line: Flucloxacillin 500mg QDS for 7 days* Facial (non-dental)
First line: Co-amoxiclav 375-625mg TDS for 7 days
Human penicillin allergy : Metronidazole 400mg TDS PLUS Clarithromycin 250- Antibiotic therapy is not usually indicated unless patient is systemically unwell. cellulitis: Co- amoxiclav 625mg TDS for 7 days*
500mg BD for 7 days. Animal penicillin allergy: Metronidazole 400mg TDS PLUS If systemically unwell and campylobacter suspected (eg undercooked meat Penicillin allergy: Clarithromycin 500mg BD for 7 days*
Doxycycline 100mg BD, for 7 days and abdominal pain), consider clarithromycin 250-500mg BD for 5-7 days, if *continue treatment for a further 7 days if slow response
treated early (within 3 days)
Rule out C Difficile infection.
Note: If meningitis is suspected, give a single dose of benzylpenicillin 1.2g IV or IM, prior to urgently transporting the patient to hospital. Alternative - cefotaxime 1g IV or IM
APLIQUEMOS LO
APRENDIDO
 UNIVERSIDAD

APLIQUEMOS LO APRENDIDO
DEL SUR

♂4a. sufre excoriación en rodilla D mientras jugaba fulbito. Al otro día

presenta T 38.2°C, dolor y flogosis perilesional de extensión creciente.
♂68a., con tos, esputo herrumbroso, disnea, dolor en HTD. Ex. Físico:
PA 97/58mmHg, P 102, R 32, T 39°C, matidez, soplo tubárico, crépitos
inspiratorios. Ex. Auxiliares: Le 12800/mm3, Ab 15%, Urea 22mg/dL.
♀24a. gestante 11ss, con disuria y polaquiuria. PPL(-). ECO: Le 18xC.
♀3a. c/diarrea x 1 día, ↓volumen, c/moco, rasgos de sangre y tenesmo.
Ex. Físico: T 38.5°C, hidratada, irritable, ↑RHA, dolor leve a palpación.
¿Cuá sería su conducta terapéutica en cada caso?
INTEGREMOS LO
APRENDIDO
 UNIVERSIDAD

INTEGREMOS LO APRENDIDO DEL SUR

✓ ¿Los antibacterianos deben ser indicados de forma

empírica o específica?
✓ ¿Los antibacterianos prescritos deben tener un
espectro amplio o reducido?
✓ ¿Es necesario ordenar cultivos previo a la indicación
de antibacterianos?
✓ ¿Qué es lo más importante para prevenir la resistencia
a los antibacterianos?
✓ ¿Qué es para Ud. el uso racional de antibacterianos?
ACTIVIDAD ASINCRONICA
 UNIVERSIDAD

ACTIVIDAD ASINCRÓNICA DEL SUR

Lectura de referencia obligatoria.

REFERENCIAS BIBLIOGRAFICAS
 UNIVERSIDAD

Referencias Bibliográficas DEL SUR

▪ Brunton L, Chabner BA, Knollmann BC. Goodman & Gilman: Las Bases
farmacológicas de la terapéutica. 13° ed. México: McGraw Hill Interamericana,
2019.
▪ Garber B, Glauser J. Recent developments in infectious disease chemotherapy:
review for emergency department practitioners 2020 [published online ahead of
print, 2020 Jun 16]. Curr Emerg Hosp Med Rep. 2020;1-6. Disponible en:
https://link.springer.com/content/pdf/10.1007/s40138-020-00218-1.pdf
▪ Kollef MH, Betthauser KD. New antibiotics for community-acquired pneumonia.
Curr Opin Infect Dis. 2019. Apr;32(2):169-175.
 UNIVERSIDAD

Referencias Bibliográficas DEL SUR

▪ Luellmann H, Mohr Klaus, Hein Lutz. Color atlas of pharmacology,

5th ed. Stuttgart, Germany: Thieme, 2017.
▪ Tyers M, Wright GD. Drug combinations: a strategy to extend the
life of antibiotics in the 21st century. Nat Rev Microbiol. 2019
Mar;17(3):141-155.
▪ Whalen K, et al. Lippincott Illustrated Reviews: Pharmacology, 7th
ed. Philadelphia, USA: Wolters Kluwer, 2019.
 dum loquimur, fugerit
invida aetas: carpe diem,
quam minimum credula
postero.
Mientras hablamos, huye
el tiempo envidioso.
Vive el día de hoy.
Captúralo.
No te fíes del incierto
mañana.
* * *
Horacio, Oda XI, Libro I.