Antibiotics for year 3 medics.pdf

ANTIBIOTICS FOR YEAR 3 MEDICAL STUDENTS
Some guidelines and information about prescribing various antibiotics
Dear StudentsI gave this to the Year 5 students and one of them said he wished he had received it in year 3, sohere it is; it is slightly modified for your revision (or more likely the first time you have ever seen orthought about it). Quite a lot is more than you need for Year 3 but I would read it through inpreparation for the exam, and particularly look at the main infections and their antibioticmanagement on pages 4 & 5; plus the bit about allergies.
Any queries, you can e-mail me.
Dr J Philpott-HowardDepartment of Infectious Diseases KCH/[email protected] CONTENTS
1. STARTING A PATIENT ON ANTIBIOTIC TREATMENT – 8 QUESTIONS TO ASK
2. RELIABLE ANTIBIOTIC SENSITIVITIES OF ORGANISMS
3. IMPORTANT ANTIBIOTIC TREATMENTS – General medical infections
4. IMPORTANT ANTIBIOTIC TREATMENTS – Dental infections
5. PRESCRIBING ANTIBIOTICS IN CHILDREN & PREGNANCY
6. ANTIBIOTIC DOSES YOU ARE EXPECTED TO KNOW
7. SPECIFIC TREATMENTS
– the patient with pneumonia
– the patient with sepsis syndrome (septicaemia)
– the patient with intra-abdominal sepsis
– the patient with meningitis
8. ANTIBIOTIC PROPHYLAXIS
– notes on surgical prophylaxis
– medical prophylaxis
– immunoprophylaxis
9. LIST OF ANTIBIOTICS (REFERENCE)
10. TABLE SHOWING BACTERIAL SUSCEPTIBILITIES (REFERENCE)
(1) STARTING A PATIENT ON ANTIBIOTIC TREATMENT – 8 QUESTIONS TO ASK
Do they need antibiotics at all, e.g. is surgery sufficient (drainage of pus is very important)? “Are you allergic to anything, or likely to be pregnant?” (see allergy note below) Is this a community or hospital-acquired infection? (the former are, in general, lessantibiotic resistant; and hospital infections (e.g. compromised) include organisms likePseudomonas which is rare in the community) Is the patient immunocompromised (more unusual or resistant organisms), or is there renalimpairment? (drug dosage, toxicity) NB What age is the patient? (dosing, toxicity e.g.
tetracyclines contraindicated, likely pathogens) Is there any positive microbiology (& have specimens been taken)? (Use narrow spectrum ifpossible; take samples especially blood cultures, before starting) What dose, frequency, duration and route (is IV needed)? (depends how sick patient is, etc) Is a combination of antibiotics needed? (e.g. neutropenia, septicaemia, endocarditis, TB,multiple pathogens likely e.g. intrabdominal sepsis) How do I monitor for treatment efficacy and toxicity? (especially gentamicin andvancomycin levels in severe sepsis; efficacy through clinical assessment, reduced fevers etc) A NOTE ABOUT ALLERGY
Allergy mainly occurs with the beta-lactam antibiotics [i.e. penicillins and cephalosporins]. About
5% of people are allergic to one or the other. ALWAYS ask about allergy before prescribing any
drug, especially a beta-lactam. About 5 or 6 people die of anaphylaxis every year, some are
avoidable by asking about allergy and checking notes/drug chart for a note about it.
• If you are allergic to one penicillin (e.g. penicillin G or V, flucloxacillin, amoxicillin), then you are allergic to all of them.
• If you are allergic to one cephalosporin (e.g. cefadroxil, cefuroxime, ceftriaxone, ceftazidime), then you are allergic to all of them.
Is it safe to give a cephalosporin to someone who is penicillin-allergic, and vice versa? Allergy to
both groups occurs in about 5-7% of people. So as a general rule about what to do:
If they have severe allergy to any beta-lactam [anaphylaxis, angioneurotic oedema, patient says
they passed out etc]: They must never have ANY beta-lactam again.
If they have mild allergy to any beta-lactam [skin rash, itching]: they can have the other type (a
penicillin or a cephalosporin)
⇒ A history of nausea or diarrhoea is not allergy.
⇒ 50% of patients with infectious mononucleosis (glandular fever) get a rash if they are given amoxicillin or ampicillin for the sore throat, which is a common presentation. This is NOT trueallergy.
(2) RELIABLE ANTIBIOTIC SENSITIVITIES OF ORGANISMS
ORGANISM
ANTIBIOTIC
NOTE
Strep pyogenes (‘group A strep’) erythromycin active but does NOTcross the blood-brain barrier sepsis usually with a cephalosporin– see later Oral anaerobes often sensitive topenicillin as well drugs in UK: may needstreptomycin, ciprofloxacin etc (3) IMPORTANT ANTIBIOTIC TREATMENTS – General medical infections
INFECTION
ANTIBIOTICS
Classically penicillin (Alternatives:
cefotaxime or ceftriaxone very often used
not cross BBB! Chloramphenicol
Haemophilus : Cephalosporins as above
Rifampicin or ciprofloxacin or
ceftriaxone for prophylaxis of close
contacts
Piperacillin/tazobactam (‘TAZOCIN’), or
resistant Klebsiella, Enterobacterin hospitals Gent enhances killing Add gentamicin if severe:once daily dose
Penicillin (or amoxicillin) &
clarithromycin [clarithro is similar to
Cephalosporin (e.g. cefuroxime) +
Gent enhances killing of organisms metronidazole
Add gentamicin if severe:once daily dose
Penicillin/Amoxycillin or Ciprofloxacin,
cephalosporins). Tetracyclines for
Chlamydia infection. Penicillin for
syphilis
Trimethoprim, co-amoxiclav
("Augmentin"), oral cephalosporins (e.g.
shows E. coli is sensitive (50%).
cefadroxil); as for septicaemia if severe Penicillin or amoxycillin; erythromycin
Many sore throats are viral. Butpenicllin may be given because of and glomerulonephritiscomplications after GAS Hospital – Clostridium difficile INFECTION
ANTIBIOTICS
Isoniazid + Rifampicin + Ethambutol +/-
Pyrazinamide NB use all four if drug
resistance cannot be ruled out
MAI complex: Clarithromycin,rifabutin, ciprofloxacin Penicillin, tetracycline
e.g. Syphilis, Borrelia (Lymedisease), Leptospira Tetracyclines, erythromycin [or clarithro]
Falciparum: Quinine + Fansidar
Other species: Chloroquine
Invasive: Amphotericin B
(topical) & fluconazole (oral/IV).
Note on some of antibiotics:
⇒ AMOXICILLIN and AMPICILLIN are more or less the same but these days
most people use AMOX because it can be given three times a day (not four)
and is better absorbed. Amoxicillin is often (wrongly) spelt amoxycillin, it is
the same.
⇒ CO-AMOXICLAV (‘Augmentin’) is souped-up amoxicillin, i.e. amox plus
clavulanic acid. The latter blocks the enzyme beta-lactamase that is
produced by some bacteria e.g. Staph aureus, E. coli, Bacteriodes (an
anaerobe present in the colon)
⇒ CLARITHROMYCIN is a new version of ERYTHROMYCIN. It is better tolerated
(fewer GI symptoms) so is commonly used. Otherwise it is similar in activity.
⇒ When we talk about ‘MRSA’ it stands for ‘methicillin-resistant
Staphylococcus aureus’. Methicillin is an old version of flucloxacillin so
really it means flucloxacillin-resistant Staph aureus. However the important
point is that these staphs are resistant to many other agents including
gentamicin, erythromycin etc. Vancomycin is reliable but recently (USA,
June 2002) totally resistant vancomycin resistant strains have been
reported.
⇒ Note that a lot of Vancomycin is also used for Coagulase-negative staph
infections (e.g. Staph epidermidis) as these are common in lines, prosthetic
implants etc., especially in high-dependency patients.
(4) IMPORTANT ANTIBIOTIC TREATMENTS – Dental infections
Dental abscess: oral anaerobes & streptococci(especially if drainage is delayed): amoxycillin OR metronidazole (or both if significant softtissue swelling); erythromycin (or clindamycin) if penicillin-allergicAcute ulcerative gingivitis: oral anaerobes inc. Borrelia amoxycillin OR metronidazole Pericoronitis: anaerobesSialadenitis: Staph aureus, Group A streptococcus etc metronidazole AND either flucloxacillin or amoxycillin (depends on cause) Actinomycosis: long-term penicillin (refer)Herpes simplex: Aciclovir creamOral candida: amphotericin B lozenges; miconazole gel (especially for denture wearers) ;fluconazole if severe especially in diabetes or compromised patientsSore throat: most viral but if Group A streptococcus: Penicillin V (5) PRESCRIBING ANTIBIOTICS IN CHILDREN & PREGNANCY
• Children are not small adults: check dosing regimen carefully • Avoid liquid formulations containing sugar • Less frequent dosing e.g. twice daily better for parents • Neonatal drug metabolism may be different e.g chloramphenicol and the liver; bilirubin • No tetracyclines or quinolones (ciprofloxacin) • Penicillins, cephalosporins are safe in pregnancy but always check the SPC (Summary of Product • Consider different organisms in children e.g. Group B strep (neonates) (6) ANTIBIOTIC DOSES YOU ARE EXPECTED TO KNOW [FOR FINALS MAINLY but a
good idea to become familiar with doses especially penicillin, erythromycin]
(Adults without renal failure)
Penicillin G (IV)
1.2 g 2 hourly pneumococcal meningitis1.2 g 4 hourly meningococcal meningitis & other severe infection1.2 g 6 hourly pneumonia Penicillin V 250-500 mg qds (oral)Amoxicillin 500 mg tds (oral or IV)Flucloxacillin 500 mg qds (oral or IV)Erythromycin 500 mg qds (oral or IV) [clarithromycin 500 mg bd]Metronidazole 400mg tds (orally, IV is 500 mg tds) Cefuroxime 0.75 - 1.5g tds (oral or IV)Gentamicin once daily 5 to 7 mg/kg/d in all patients (in endocarditis we still use the older twice- orthree-times-a-day dosing in hospitals where once-daily gent not used) then adjust according toGENT LEVELS, NB renal function.
(7) SPECIFIC TREATMENTS OF SOME INFECTIONS [this is finals standard but gives
you an idea that there is more than one option – need to consider especially
severity, immunocompromised status]
THE PATIENT WITH PNEUMONIA
Immunologically OK, from community
Ø Mild to moderate pneumonia (pneumococcus, haemophilus, atypicals) è amoxycillin & either
Ø Life-threatening (above + Legionella or Staph aureus) è ceftriaxone & erythromycin or Ø TB: Isoniazid, rifampicin, pyrazinamide, ethambutol Immunologically OK, hospital-acquired pneumoniaØ Not too unwell (could have aspiration pneumonia) è amoxycillin (or cefuroxime) (& Ø Life-threatening, or already on ITU è ceftriaxone & metronidazole, possibly a dose or two of Transplant or leukaemic (could be anything)Ø Not too unwell (and NOT neutropenic) è cefuroxime + amoxiillin (or oral ciprofloxacin + Ø Deteriorating rapidly or neutropenic è piperacillin-tazobactam (‘Tazocin’) ± gentamicinØ NBConsider Aspergillus, pneumocystis, CMV etc. – urgent bronchoscopy HIVØ Pneumocystis è High dose cotrimoxazoleØ Common bacteria è as for community-acquired pneumoniasØ TB as above; other mycobacteria e.g. MAC see earlier THE PATIENT WITH SEPSIS SYNDROME (SEPTICAEMIA)
Origin unknown
è Piperacillin-tazobactam (‘Tazocin’) ±gentamicin
If known source & not too unwell - treat according to likely pathogens. Alternatives: ‘Timentin’,
ciprofloxacin, ceftriaxone or cefotaxime.
THE PATIENT WITH INTRA-ABDOMINAL SEPSIS
e.g. perforated gut, post-operative disaster area
è cefuroxime + metronidazole;
or if severe piperacillin-tazobactam ±gentamicin
THE PATIENT WITH MENINGITIS
Rash: (i.e. ?meningococcal septicaemia with or without meningitis) è immediate IV or IM
penicilllin G given by GP or in A&E before any investigations lumbar puncture
Adult purulent CSF: (Meningo, pneumo): Penicillin but increasingly ceftriaxone (or cefotaxime in
some hospitals) is used
Child purulent CSF: (as above plus Haemophilus - now rare due to Hib vaccine): ceftriaxone (or
cefotaxime)
Neonate: Penicillin + gentamicin +/- ceftazidime
Brain abscess: Ceftriaxone (or cefotaxime) + metronidazole but depends on history e.g. recent
neurosurgery
Lymphocytic CSF: Viral but ??TB (or rarely Listeria); ??Herpes simplex encephalitis - aciclovir
HIV, transplant: Cryptococcus, toxoplasma (8) ANTIBIOTIC PROPHYLAXIS
Prophylaxis is the administration of a drug to prevent a disease. Antibiotic prophylaxis, is strictly
speaking, given before the host encounters an infectious agent. However in general use it also includes
post-exposure prophylaxis e.g. after a high-risk wound such as a human or animal bite, the wound is
cleaned and the A & E clinician gives antibiotics to prevent clinical infection; e.g. some agents are used
long-term to prevent relapse or re-infection such as recurrent urinary tract infection.
NOTES ON SURGICAL PROPHYLAXISThe main principles are: • short course, e.g. single dose or no more than 24 hours in most cases • use antibiotics appropriate for the expected organisms • use antibiotic according to surgical department’s policy* • start antibiotic just before the procedure (in anaesthetic room or with pre-med) * e.g.
Orthopaedics, cardiothoracic: {prevent mainly staph infections, occ. Gram negative]cefuroxime, or flucloxacillin + gentamicinAmputation: [prevent gas gangrene due to Clostridium perfringens) penicillin or metronidazoleAbdominal surgery: cefuroxime and metronidazole or co-amoxiclav (‘Augmentin’)Neurosurgery: penicillin + flucloxacillinObstetrics & gynaecology: [prevent anaerobes, streps] co-amoxiclav MEDICAL PROPHYLAXIS:Neutropenics: oral amphotericin B or fluconazole; ciprofloxacin in BMT (follow department policy)Sickle cell disease patient; rheumatic fever; splenectomy: Oral penicillin (‘penV’) (+vaccines forpneumo, meningo)Cardiac abnormality (prosthesis, abnormal valves) and patient is for dental or other bacteraemia-inducing procedures: LA: amoxycillin orally, or clindamycinGA: Amoxycillin or amoxycillin + gentamicin or vancomycin+ gentamicin (depends on risks -see Formulary, contact a Medical Microbiologist) HIV: Zidovudine+lamivudine+indinavir after a high-risk needle injuryMeningococcal disease contact: rifampicin or ciprofloxacin.
IMMUNOPROPHYLAXIS:e.g. hepatitis B vaccine and/or specific immunoglobulin after a needle injury; varicella-zosterimmunoglobulin (VZIG) in a compromised person after exposure to chickenpox; also rabies, hepatitis A,measles etc.
Long-term IV immunoglobulin in a hypogammaglobulinaemic child.
LIST OF ANTIBIOTICS
(10) This is for reference only, antibiotics are classified by type.
An antibiotic is a substance produced by a micro-organism which inhibits growth of, or kills,another micro-organism; the term antimicrobial extends this definition to include agents such assulphonamides which are not products of micro-organisms. Antibiotics and antimicrobials areactive in low concentrations, unlike antiseptics and disinfectants which are often used as 1% or 2%solutions. Classification of antimicrobials according to their principal range of activity: a) Active mainly against Gram-positive bacteria & Gram-negative cocci
Standard penicillins
Benzlypenicillin (Penicillin G), Phenoxymethylpenicillin (Pen V, oral)
Antistaphylococcal penicillins
Flucloxacillin (Methicillin: now only used in laboratory sensitivity testing; if
resistant to methicillin then Staphylococcus aureus is resistant to flucloxacillin
(“MRSA”)
Other agents
Erythromycin (often for penicillin-allergic patients), vancomycin (for MRSA)
(but Vancomycin is not active against Gram-negative cocci)
Fusidic acid (Staph aureus)
Mupirocin (topical anti-staphylococcal agent, especially for MRSA)
b) Active mainly against Gram-negative bacilli
For systemic infections:
Penicillins (NB most retain activity against streptococci)
e.g. ampicillin, amoxycillin (many uses e.g. respiratory infection, dental
prophylaxis)
e.g. piperacillin (broad-spectrum: for severe infections used together with
gentamicin)
e.g. co-amoxiclav (“Augmentin”) which is amoxycillin plus clavulanic acid
(clavulanic acid inhibits bacterial β-lactamase)
e.g. piperacillin-tazobactam (“Tazocin”) (tazobactam inhibits bacterial β-
lactamase)
Aminoglycosides e.g. gentamicin, streptomycin
ii)
For urinary tract infections only: Nitrofurantoin, nalidixic acid,
norfloxacin
iii)
Topical use: Neomycin; Polymyxins, e.g. colistin Broad-spectrum antibiotics
Cephalosporins e.g.
cephalexin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime
Carbapenems e.g. imipenem, meropenem
Sulphonamides; cotrimoxazole (trimethoprim + sulphamethoxazole)
Trimethoprim; tetracyclines; chloramphenicol; ciprofloxacin
Anti-anaerobic agents e.g. metronidazole, clindamycin
Antimycobacterial agents
e.g.
isoniazid (INAH), rifampicin, ethambutol, pyrazinamide, streptomycin
MODE OF ACTION & FURTHER INFORMATION ON ACTIVITY – main ones in bold
1)
Penicillins and cephalosporins These act by interfering with the cell wall of growing
bacteria; they inhibit biosynthesis of mucopeptides which cross-link previously formed
peptidoglycan polymers, and cells undergo lysis. They kill bacteria i.e. are bacteriocidal,
asopposed to some other antibiotics that inhibit only (bacteriostatic).
Penicillin V(oral) and PenicillinG (IV – ‘benzylpenicillin’) are active against only 10-
20% of Staphylococcus aureus strains and against most streptococci; viridans streptococci
and recently some strains of Strep pneumoniae are sometimes resistant. Gram-positive rods,
spirochaetes, meningococci and most gonococci are penicillin-sensitive; the majority of
anaerobes (except Bacteroides fragilis –which is mainly found in the colon) are sensitive.
Oral anaerobes are all penicillin sensitive. Penicillin V is only used for minor infections as
it is not well absorbed.
Ampicillin and amoxycillin have similar activity to penicillin plus activity against
Haemophilus influenzae (10-15% resistance); enterococci; they are active against 50% of E.
coli and some Proteus, but Klebsiella is resistant). Amoxycillin is better absorbed orally
than ampicillin.
Ticarcillin, piperacillin and azlocillin are active against Pseudomonas spp, and also have
broad-spectrum activity against many Gram-negatives. Piperacillin/tazobactam is also
active against Staph aureus, streps and anaerobes (tazobactam is a beta-lactamase inhibitor
like clavulanic acid (in ‘Augmentin’) which extends the spectrum of the piperacillin).
Flucloxacillin is used only as an antistaphylococcal agent although it does retain some
penicillin-like activity.
Cephalosporins The earlier cephalosporins (e.g. cephalexin – not used much in UK) are
more active against Gram-positive bacteria than the later ones such as cefuroxime,
ceftriaxone and cefotaxime, which all have useful activity against enterobacteria
(coliforms) and Haemophilus. In general cefuroxime is used for surgical prophylaxis,
hospital-acquired chest infections and severe UTI. Ceftriaxone (which is given once a day)
and cefotaxime are very similar and are reserved for severe pneumonias, some meningitis
and septicaemias. New One cephalosporin is also very active against Pseudomonas spp. i.e.
ceftazidime.
Erythromycin This bacteriostatic macrolide antibiotic interferes with protein synthesis by
ribosomal binding. It is used in penicillin-allergic patients against staphylococci,
streptococci and Gram-positive rods but also has activity against Campylobacter, Bordetella
pertussis, Legionella pneumophila, mycoplasmas and chlamydiae. Erythromycin does not
penetrate the CSF - so is of no use in meningitis. Azithromycin & clarithromycin are
newer types of macrolides with longer half-lives and fewer side-effects.
Chloramphenicol also binds to ribosomes. It is bactericidal against streptococci and
haemophilus, but only bacteriostatic against enterobacteria. Owing to toxicity (bone marrow
suppression, aplastic anaemia) this drug is reserved for occasional therapy of meningitis (esp
in developing countries), typhoid fever and topical treatment of eye infections.
Sulphonamides and trimethoprim These agents block the synthesis of bacterial
nucleotides in the pathway of folic acid/nucleotide synthesis. Active against Gram negative
bacteria & Pneumocystis (e.g. in AIDS). Trimethoprim is used a lot for UTI.
Sulphonamides can have nasty side-effects e.g. Stevens-Johnson syndrome & bone marrow
aplasia.
Aminoglycosides e.g. gentamicin, interfere with ribosomal reading of messenger RNA.
Although not active alone against streptococci they exhibit very useful synergy with
penicillins against these and other organisms. They are used principally in serious sepsis
with coliform organisms and Pseudomonas (and always in combination with, for example, a
cephalosporin or broad-spectrum penicillin – also in endocarditis with penicillin G). Theyare not active against anaerobes. Aminoglycosides penetrate the CSF poorly.
The potential VIIIth nerve and renal toxicity of these drugs means that serum levels must bemeasured or alternatives used in patients receiving other nephrotoxic agents or if they haveimpaired renal function.
Metronidazole affects nucleic acid function by breaking DNA strands. It is active against
all anaerobes, amoebae and Trichomonas vaginalis, and is well absorbed with good
penetration into abscesses and CSF. Also used a lot in gut surgery as prophylaxis or
treatment. Peripheral neuropathy may occur with prolonged therapy. Tinidazole is similar
Tetracyclines e.g. oxytetracycline, doxycycline, are bacteriostatic (see note under
penicillins, above), and inhibit binding of transfer RNA to the ribosome. Although used
infrequently for ‘conventional’ bacterial infections, they have useful activity against
chlamydiae, mycoplasmas, rickettsias and Coxiella burnetii as well as staphylococci,
streptococci and some Gram-negative rods. They must not be used in pregnancy, in children
or in renal impairment.
Quinolones e.g. ciprofloxacin, inhibit DNA gyrase, the enzyme that 'winds up' DNA inside
the bacterium. The organisms are disrupted by the unwound DNA. An important interaction
is the potentiation of theophylline, otherwise they have few side effects. Used for problem
UTIs, infections in compromised patients, typhoid fever and even in some cases of TB.
LABORATORY ASPECTS OF ANTIBIOTICS
Although some bacteria have predictable sensitivity patterns, for example group A streptococci are
always penicillin-sensitive, antibiotic sensitivity tests are performed on all significant bacterial
isolates from clinical specimens. In this way, the suitability of the patient's therapy is assessed and
current trends of bacterial antibiotic resistance in the hospital and community are followed.
Antibiotic sensitivity is also helpful in identification of organisms, e.g. anaerobes are recognised by
their uniform sensitivity to metronidazole. The antibiotic disc test is the most commonly used. If
production of beta-lactamase can be demonstrated using certain rapid chemical tests, then resistance
to antibiotics such as penicillin or ampicillin can be assumed. The minimum inhibitory
concentration (MIC) and minimum bactericidal concentration (MBC) of an antibiotic against an
organism are sometimes measured as they are more precise measurements of antibiotic
susceptibility than the disc test. For example, a blood culture isolate of Streptococcus salivarius
from a patient with endocarditis has penicillin MICs and MBCs performed: MIC = 0.03 mg/l, MBC
= 0.12 mg/l; this means that the organism is inhibited from growing at 0.03 mg/l and killed at 0.12
mg/l. Antibiotic levels: Blood levels of toxic antibiotics such as the aminoglycosides or
vancomycin are measured, particularly when there is impairment of renal function.
REFERENCE TABLE of antibiotic activities overleaf – also for reference only
Colour relates to Gram stain…if that helps… ANTIBIOTIC
Staph
MRSA
Strepto-
Entero-
GC &
Coli-
Haemo
Pseudo
Anaer-
Spiro-
Chlamydia,
TB
aureus
& CNS
cocci
coccus
Meningo
forms
-philus
-monas
obes
chaetes
mycoplasma,
rickettsias
cefadroxilInjectablecephalosporins:Cefuroxime (4) = poor activity, resistance common or not appropriate for therapy

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