‘THERAPEUTICS OF INFECTION Mechanism of action of anti-bacterials Target Drug ex, Cell wall Glycopeptide Vancomycin Beta-lactam Penicillin Cephalosporin Carbapenem — Meropenem Nucleic acid — Riftmpicin Quinolone Ciprofloxacin Sulphonamide Trimethoprim Ribosome AminoglycosideGentamicin Tetracycline Doxyeyeline Chloramphenicol Macrolide Erythromycin Fucidie acid EXTRACELLULAR BACTERIA Inhibits synthesis of petidoglycan cross-linking of peptidoglycan alycan king of peptidoglycan gene transcription DNA gyrase folic acid synthesis folic acid synthesis mRNA attachment {RNA attachment peptidy! transferase polypeptide translocation polypeptide translocation cida/static cidal/static 1 Entero Staphylococci Streptococci VRE MRSA _MSSA ‘Gram negative cocci Gram positive cocci Gram positive bacilli 2 ‘Susceptible Gram negative bacilli 3 Non-sporing Multi-resistant Anaerobes Pscudomonas_ESBL Bacteroides [Elucloxacillirl [Benzylpenicillin ] {Gentamicin} (Aztreonam] Eucidic acid {Erythromycin (Ciprofloxacin) Eosfomycid Quinupristin/dalfopristin (Co-trimoxazole, Ceftazidime: ‘Amoxycillin + Clavulanic acid = Au, in) [moxy +Clav] t Piperacillin + Tazobactam = Tazocin I [Pip sha) ‘Meropenem INTRACELLULAR BACTERIA 4 5 [Pyrazinamide] [Erythromycin] EthambutolSepticaemia ‘© Primary community-acquired septicaemia ‘+ Community-acquired septicaemia with a local focus ~ skin, urine, chest Septicaemia in a hospitalized/immunosuppressed patient Chronic septicaemia Primary community-acquired septicaemia Neonate Child Adult Ecoli Meningococeus Staphylococcus aureus Group B Strep Pheumococcus Group A streptococcus Listeria Haemophilus Pneumococcus Meningococeus E.coli ‘Acute community-acquired pneumonia syndromes ‘Typical “Atypical” Prodrome short long Sputum + He Haemoptysis +h - Chest signs focal diffuse, subtle Consolidation on CXR focal focal or diffuse Aspiration variable +H He focal focal +/- cavitation, collapse Associated features rash impaired consciousness | vomiting, diarrhoea renal impairment || liver impairment Actiology endogenous corm ~ endogenous extracellular bacteria | tracellular bacteria | extracellular bacteria Pheumococcus Legionella anaerobes, Haemophilus Chlamydia Bcoli, Klebsiella Coxiella Mycoplasma Infectious diarrhoea syndromes ‘Non-inflammatory Inflammatory Watery Dysentery Location jejunum ileum, colon Stool large volume, watery small volume, loose, often bloody Pus cells in stool - + Redcells in stool - + Fever - + Chronic watery Acute watery Acute dysentery Norovirus Rotavirus EE) Clostridium difficile ee] Campybotacter Salmonella ee Shigella E.coli (EPEC, ETEC) E.coli 0157 Vibrio cholerae Giardia Cryptospori Vibrio parahaemolyticus Entamoeba histolyticaBacterial meningitis, Neonate Child/young adult Elderly E.coli Meningococcus Peumococcus Group B Strep Pneumococeus Listeria Listeria Haemophilus rarely Meningococcus, Haemophilus, E.coli Infection in an immuno-compromised patient Inherited Acquired Organisms ‘Neutrophils B lymphocytes ‘Tlymphocytes Chr granulomatous dis Agammaglobulinaemia Koshwwund Sy/0Gns Common variable immuno-deficiency Hyposplenism/ splenectomy Sickle cell disease Marrow failure Leukaemia (CLL) Hodgkins Coeliac disease leukaemia Lymphoma HIV drugs Myeloma Organ transplants Endogenous bacteria Bacteria “Mycobacteria Capsulated bacteria Candida esp. Pneumococeus Fungi (PCP) Pneumococcus Aspergillus VZV, CMV Haemophilus Toxoplasma Neisseria Persistent unexplained fever (Pyrexia of Unknown Origin) 4 categ 1. Infection 2, Tumour 3. Connective tissue disease 4, Other Approach Abscess, osteomyelitis, endocarditis ‘Tuberculosis, brucellosis HIV Immunosuppressed patient with mycobacteria or Lymphoma, leukaemia, renal carcinoma, mesoth Drugs, factitious, recurrent PE, Crohns protozoa or fungi yelioma Rheumatoid, SLE, Stills disease, systemic vasculitis Repeated careful clinical examination (including rectal ‘vaginal examination) Review all previous medical notes + write a cumulative results chart Week 1 Week 2 FBC, ESR iff indicated Blood films for malaria URE, LFT, CRP Blood culture x3 MSU Stool C&S Serology for HIV, brucella Vasculitis tests Rh factor, ANA, ANCA, complement Urinalysis, microscopy for cellular casts CXR Echo Tuberculin test! M.tuberculosis T-spot CT scan chest & abdomen Tissue biopsy White cell scan Liver biopsy Bone marrow aspirate & trephineWHICH ANTIBIOTIC FOR WHICH INFECTION? CORE KNOWLEDGE expected of students at Pathology Finals is given in large print. WOUND AND SOFT TISSUE INFECTION CONDITION ORGANISMS ANTIBIOTIC TREATMENT. DURN = v.qood Srep Infection following trauma, | Staph. aureus PO Flucloxacillin rage — | S74 clean surgery, 1V lines P-Haem Strep A,B,C,G | (Brythrd/Tetra) 4 petvculeryic If MRSA risk factors (see note 5): TV vaneomyein (coliforms) (add ceftazidime*/ciprofloxacin /gentamicin if severe) (Clost. tetaniy Check immune status + Diny surgery (oro a mucous As above, plus lol fora PO Co-amoxiclay sd membrane) Eg. Anserabes & coliforms in| IV Pen (vancomyein if MRSA risk factors) + ut surgery Gent + Meto (Close ttan) Human bite (prophylaxis and Staph, onrens PO Co-amoxiclay sa ‘ecament) Sweps Eyl + Metro) 10 if severe Anserobes (Clost tetani) Animal bite (prophylaxis and As above PO Co-amoxiclav sa ‘reatment) plus Past. multocida (Cipro* Metro) 10d if severe Capnocytophaga (Cast. tetani) ‘Rabies virus) Decubitus ulcers Staph. aureus PO Flucloxacillin 7-104 (& severe B-Haem Strep A.B,C,G : foo infections in diabetics) (Anaerobes) (Metronidazole) (Coliforms) (Ciprofloxecin) Severe or unresolving: add Meto, or Co- amoxiclav monotherapy) Cellulitis in General Practice | Staph aureus flucloxacillin (erythromycin) 5-10 days (and erysipelas, if diagnosis | haem Strep A, B, C, G uncertain) Erysipelas Bhaem Strep A penicillin V (erythromycin) only if | 7-10 days diagnosis certain i Staph aureus ‘Topical Fusidate or Mupirocin 7 days petigo, é a nected ecpetin: B-Haem Strep plus PO flucloxacillin A,B,CG) (erythromycin) if severe SaysWOUND AND SOFT TISSUE INFECTION CONDITION ORGANISMS, ANTIBIOTIC TREATMENT. DURN Otitis extema mild As below topical neomyein: Betnesol N, : Otosporin days neomycin + polymixin 1NB: cleaning essential PO fluctoxacilin (erythromycin, 5 days if'severelcellulitstboit ‘Staph aureus ‘conamoxiclav) & empirical _ Bhaem Strep A, C, G PO penicillin V Says Pseudomonas aeruginosa PO ciprofloxacin S days (refer urgently suspected malignant otitis externa tv gentamicin or cefazidime then oral 6-24 weeks cipeofloxac fungi (dermatophytes, yeasts, | topical clotrimazole (nystatin) 2 weeks after moulds) clinical eure ‘Comeal or conjunctival infeetion | Staph. aureus ‘Topical chloramphenicol, or L-2wks Sirep. pnewnoniae gentamicin or continue 24 Hen. influenzae Coliforms (Fucithalmic if Staph) afer cure Pseud. aeruginosa Nelss. gonorrhoeae ‘Topical penfgent 3d H/=IV ceftriaxone / cefotaxime Chlamydia ‘Topical TetaErythr0 wks 41-PO erythro Viruses topical acyclovir eye ointment for 3d after Herpes simplex healsUROGENITAL TRACT INFECTION CONDITION ORGANISMS ANTIBIOTIC TREATMENT ___| DURN Empirical: Simple cystitis | Esch. coli PO Cephalexin 3a (woman with no | Prot mirabilis Trimethoprim ial? Ren AN) abnormality of ‘Soph sareniyites Nor/Oflox/Ciprofloxacin Urinary Tract) Enterococcus faecalis (Co-amoxiclay) iv Mospirul (Nitrofurantoin) SOL YU AAW (0 axon ULL A Cystitis, Child As above As above (not Nor/OfloxCipro) | 74 Cystitis, Pregnant | As above As above (Beta-lactam or 7104 Nitrofurantoin, only) Complicated lower UTI] Asabove, plus PO Nonieiprofloxacn or 1a (ales, catheter, stone | other cottons, 1W cipro oF gentamicin or ete) Peeud. aeruginosa, cefotaxime ‘Staph. epidermidis sensitivities Candida albicans (POIIY Fluconazole or IV Amphotericin) Pyelonephritis As above Severe/vomiting: IV Cipro/Gent/ Cefiriax/Cefotax then 104 PO Norlciprofloxacin Mild: PO Nor/ciprofloxacin If unresponsive to above: meropenemvimipenem Vaginitis Cand. albicans Topical antifungal 1d 2px Trich. vaginalis PO Metronidazole Anaerobic vaginosis PO Metronidazole or a (Gard. vaginalis) topical Clindamyein Post-op/Post-delivery Staph. aureus ‘Severe: IV ceftriaxone / cefotaxime + Metro, | Id sage infetion B-Hlaem Strep A, 8 then PO Cosamoxi Anaerobes 4 Urethiis, eles gonorrhoeae IM ceftriasone/ cefotaxime spetinomysin | dose carvicits PO Cefixime ose (PO ciprofloxacin) Tose Chom, trachomatis PO Doxyexeine 7 Or aaitnomycin doseUROGENITAL TRACT INFECTION CONDITION ORGANISMS: ANTIBIOTIC TREATMENT. DURN Epididymo-orehitis Esch, coli (235 yrs) PO ciplofi/norfloxacin (>35 years) 10 days Chlam. trachomatis (<35 yrs) | PO doxyeyeline 100 mg bd (<35 yrs) 14 days (eis gonorrhovae 35 yrs) __| PO cefixime (cipiotloxacin) Tadays Prostatitis Asabove PO CipeoiDoxyeyeline 4uwks Pelvic inflammatory Chlam. trachomatis PO doxyeyeline 100 mg ba plus: either 14.21 days disease Anacrobes PO metronidazole 200 me tds 14 days (Geis. gonorrhoeae) ‘or eovamoxiclay 625 mg tds 14 days Wo-2ta Syphilis Trep. pallidum IM procaine penicillin Note: Refer patient to Dept Genito-Urinary Medicine if'an STD diagnosed for contact tracing, confirmation, of eure and syphilis serology.GUT-RELATED INFECTION CONDITION __| ORGANISMS ANTIBIOTIC TREATMENT DURN Infective diarrhoea, (Empirical Empirical therapy PO Ciprofloxacin, consider sd therapy only if | (community-acquired) additional metronidazole iftravel | 5g severe or and very severe (protozoa) debilitated host) suapronnaric. | Cammtoticee PO Erythromycin (ciprofex) Pr L- | Salmonetia PO Cprofloxacin (imei) WONTROL- | Sc : ne CONSIDER | Yenini : ) VURAL CAUSE. | rch cot 0157 ‘Avoid antibiotic in Esch. coli 0157 as it increases incidence oofhaemolytic uraemie syndrome Gierdia PO Metronidazole a Ent. histolytica PO Metronidazole then Sd PO Diloxanide 108 Clost. difficile PO Metronidazole, or vancomycin | 194 & Empirical therapy for | if'severe hospital-acquired infe Cholecystitis, Exch, colt Mild: PO Co-amoxiclay Cipro sa Cholangitis Coliforms Enrerococet Severe: IV Cefraxone®/ Ceforasinet / Tetod total (Anaerobes with siete) Gentamicin / Ciprofloxacin then PO as above Faecal peritonitis | Bxch colt IV Penisilin r-t0a Cottons + Gentamicin Cipro (Ceftrianone*/ Bnverococi Ccfotaxime) Bacteroides sep. “+ Metronidazole Liver abscess Sire. miler IV Ceftriaxone /Cefotaxime®/ Amox *Gent/ | 28d or longer Coliforms Ciprofloxacin, Anaerobes all + Metronidazole, then oral Co-amoxielav (note: drainage important) Entamoeba histolytica PO Metronidazole 5-10d |_(Plus intraluminal amoebicide) ‘Typhoid fever Salmonella para/typht IV/PO Ciproftox / Ceftriaxone / Cefotaxime | T-14d (zithromycin / chloramphenicol) oUPPER RESPIRATORY INFECTION CONDITION ORGANISMS ANTIBIOTIC TREATMENT. DURN Severe sore throat, | B-Haem Strep A (C,G) PO Penicillin V (Ey) S04 tonsillitis Coryne. diphtheriae PO Erythromycin (PenV) rad Candida albicans PO Nystatin (fluconazole) i Acute eels Hom: inftuersae b IV Cofrinxone* /Cefotaxine* 14 supragloiis Getinem Step Gp A (Chloranphenicl, “Amoxil, Severe acute otitis media | Strep pneumoniae PO Amoxicilin, Erythromycin (Co-ameniclav it | $a (etinem Step Op A no response) Hoom infencae Mica pneumoniae Severe acute sinsts Assbove PO Amox sa Plus Staph aureus in ronal sinusiis |_PO Co-unonila if fontal Chronic suppurative otis | As above phos PO Metronidazole es edi, “Anaerobes plus ciproffoxacin chronie sinusitis Colitorms Pseudomonas Often mixedLOWER RESPIRATORY INFECTION CONDITION ORGANISMS ANTIBIOTIC TREATMENT. Empirical: yued_, *Muagy ‘Acute exacerbation of | Strep. pneumoniae Amoxicillin / — powycline 5d chronic bronchitis, Hem. influenzae (Co-amoxiclay, Tetracycline, (Bran, catarrhalis) Clavithro/Erythromycin, Trimethoprim, Cipro/Ofloxacin) Pneumonia, community Empirical: ee acquired Strep. pneumoniae ‘Ayypicals’: Myco. pneumoniae Chlam. psittaci Chlam. pneumoniae Cox. burnetii Legion. pneumophila PO Amoxicillin [+ Ery/Clarithro if unresponsive or moderately severe (covers atypicals)] IV. ceftriaxone* / cefotaxime* + Erythromycin (or pen G + cipro if>65y, to reduce risk of Ccdificiedarthoea with IV cephs) extend erythromycin to2-3wk itarypical confirmed Friipiieal 14 Posteinfluenzal, as above, | Empltical: fea opeoalle PO Co-amoxiclav or pene Flucloxacillin + Erythro/clarithro, cree TV as above Haem. influenzae 5 : “a 1 a (COAD/COPD) Amoxi/co-amoxiclav ‘Anaerobes (if aspiration) | add Metronidazole to the above | 4 Influenza A Oseltamivi sa Ventilator-assocsted pneumonia. | Coliforms Cetviatone /Cfvatine 78 Peeud. aeruginosa Gproffonacin'Cetzidime Staph aureus Ficlossiin Mesa ‘Vancomycin pirical: 1V Ceftriaxone /Cefotoxime if admission 5d since admission ‘ane + Meroimipenem ifsevers oF Untesponsive othe sbove Hosita-acquted aspiration | Asabove as sbove 114 pneumonia ‘oral Anaerobes plus IV/PR metronidazoleLOWER RESPIRATORY INFECTION CONDITION ORGANISMS: ANTIBIOTIC TREATMENT DURN Pneumonia in T cell Iymphopenia Pneumocystis earint Mycobacterium tuberculosis Mycobacterium aviurt IV>P0 High Dose Cotrimoxazole PO Riftisopyra +/-th, then RIFHS0 PO Clarithromycin + rfabutin + ciprofloxacin 2bwks 2mo then 4-7mo Fungi: 6-12Wk Aspergillus funigatus(flarus | IV Amphotericin 6k Onypio, neoformans IV Ampho*Flueytosine (raconazole) Viruses (Fluconazole) HSV, VZV, 10d aciclovir cu 10a ganciclovir Community acquired lung. ‘Strep. pnewnoniae PO Pen/Fluctoxacilin 2-4 months abscess ‘Steep. milleri +Metronidszole, ‘Staph aureus or co-amoxielav alone Anacrobes| asabove asabove 2s empyema note: drainage importanton diagnosis by GP 300 mg for children <1 yr (ifprevious anaphylaxis to peneilin then consider IM/IV cefotaxime!ceftriexone or chloramphenicol) MISCELLANEOUS CONDITION _| ORGANISMS ANTIBIOTIC TREATMENT DURN Endocarditis | Viridans-Type Streps IV Penicillin M284 ‘++ gentamicin (low dose) Meningitis, Empirical: 1V child/adult Neiss, meningitidis Cefiriaxonelcefotaxime Attest 5 days Strep. pneumoniae IV Pen G/ Ceftriax/cefotax 10.1 Haem. influenzae IV Pen G/ Ceftriax/cefotax i IV Ceftriax/cefotax List. monocytogenes a 1V Amp/Amox plus gentamicin (not Ceftriax/cefotax!) neonate Esch, coli : aa {p-Haem Strep B IV Ceftriax/cefotax tala List. monocytogenes IV Pen/Amp (Cefiriax/cefotax) 12a IV PeniAmp (not Ceftriax/cefotax!) Meningococcal } Neiss. meningitidis benzylpenicillin (IM or IV) Stat, plus urgent meningitis or Sousa referral for Rx as septicocm tact. above Brain sbscess Step mile group Expitcal “Anaerobic Steps, IV Cefoiaxime + metronidazole. 2awks Bacteroides, then, S.cureus PO Conamoilav wks to 6x (Rea mixed) (cote: drainage important) Osteomyelitis | Staph. aureus Empirical: 450k (Strep. pneumoniae) IV->PO Fluclox (G-Haem Streps) 6y and unvaccinated against Haem. (Coliforms) influenzae: Cefwiaxoneleefotaxime (acm. influenzae) ‘or Co-amoxiclav Arthritis As above, but non Empirical: 240k staphylococcal more common and plus N. gonorrhoeae TV Fluclox + Cipro, or Cefiriaxone*/Cefotaxime* monotherapy ‘Then PO Co-amoxiclavMISCELLANEOUS CONDITION _| ORGANISMS ANTIBIOTIC TREATMENT. DURN. Orafacial Strep miller group, Enpitial Odontogenie Anaerobic steps ‘ilé- PO pen or erythromycin 14 Infections Bacteriodes (not B. frais) (dental abscess ‘moderate- PO Co-amoxiclay, or erythromycin + | 7-104 Ludwig's angina, ete) ‘metronidazole severe - IV pen gent, or ceftriaxone / cefotaxime, all plus metronidazole (note: drainage important) 2-Sd thea as above Ontulcerwith | Asatove pus empitial:co-amoxilay Says cellulitis: Bhacm streps, Staph aureus Malaria Plasm, falciparum Quinine 14 other spp. Chloroquine a Septicaemia | Streptococci: Empirical initial rv Ts104 B haem, pneumococci, 4) community-acquired (enterococci) ceftriaxone /cefotaxime*, + Staph, aureus (MRSA - hospital) Neisseria Coliforms (Pseudomonas - in hospital) Possible anaerobes (e.g. bowel perforation) metronidazole or penG +ciprofloxacin+metronidazole +b) hospital acquired: 1V vancomycin (as MRSA possible) + gentamicin'/ceftazidime'*/ piperacillin-tazobactam! ciprofloxacin'/ + metronidazole Note ‘for coliform plus anti-pseudomonal cover. Use imi/meropenem instead if previous patient had previous resistant coliforms or Pseud., or fails to respond 10VIRAL INFECTIONS: CONDITIONS ORGANISMS ANTIBIOTIC TREATMENT DURN Shingles Varicella zoster | PO famciclovir or valaciclovir Tdays virus (probably beter for controling pin, especially i given <48-72 hrs er onset of symptoms but in pregnant women give valaciclovir because the active ingredient acilovr has been shown tobe OK in pregnancy). famciclovir 750 mg x My. cally start <48-72 hs afer onset Chicken pox Varicella zoster | PO aciclovir s00mgx say for immunocompetent | 7s virus adults/adolescents with severe disease ut ava keep an ye open om ads fx development of cepa eurnni. Ge the toring dally rake net chsk al. ey do {elope ietretening completions, send thes medal t0. esp for TV aciovr treatment. Immunocompromised patients with severe chickenpox should always be given IV aciclovir. old sores Herpes simplex _| Topical valaciclovir x situy Says virus Jenital herpes Herpes simplex | Oral famciclovir: ints first episode 250 mg tds Says ‘Acute recurrence 125 mg bd Sdays aviclovir: ftepinde200 me nes dy. tt eiterasoiting ih | ays Acute recurrence 400 mg bd Stabe ASV encephalitis | Herpes simplex __ | 1V acielovir (must be 10 mg/kg ts) Al east 10 days virus av see lecture notes 11Notes: |. "Third generation cephalosporins should be avoided in adult patients whenever possible, as these ate strongly associated with the development of Clostridium difficile-associated diarrhoea 2. ( ) = 2nd line antibiotics, usually because of resistance, occasionally cost. If used in General Practice, send a specimen to confirm sensitivity. Bracketed organisms are found infrequently. 3. Where erythromycin is stated, clarithromycin or azithromycin can be substituted when improved GT tolerance and bd regimen more important than cost. 4, Fluoroquinolones (eg cipro/nor/levo-floxacin) may be used in childhood as 2nd line therapy when potential benefit outweighs theoretical risk of joint damage. 5. Inthis document"/" means: "or", mof "and"! 6. Methicillin Resistant Staphylococcus aureus (MRSA) are resistant to all -lactam antibiotics and many other first-line antibiotics. All local strains remain susceptible to the parenteral antibiotic vancomycin, most are also susceptible to tetracyclines. Almost all of the infections caused by this organism are acquired in hospital or residential care, Virtually all the infections seen in General Praetice occur in patients with the following risk factors: * Recently discharged from hospital © Nursed in residential home with MRSA-positive residents © Infection in a known carrier of MRSA. SH Aliyu 12.5.1 ic rms. 5 « Noovormia Specie, i (not ator bee MBA Wor Vancomycin OLAL © —~ YH MRIA give doxycycline vr Olo- amo xi clare Giarovin - preudomonran necperwm - Evenced prema B lactamase Codif 2 Ora mruenmdurwe Oral Vancomyan 12