Antibiotics: What are they & How they are used Dr Rob Townsend Consultant Microbiology NGH

Uses of antibiotics 1) Treatment 2) Prophylaxis a) Specific indications endocarditis post-splenectomy b) Prevention of post-surgical infection

Antibiotic Prophylaxis Timing and duration to be effective you require highest tissue concentration of antibiotic at time of surgery. Importance of foreign material i.e. remove it! Prophylaxis generally not indicated in clean surgery except for prosthetic surgery

Antibiotics - Overview Many different classes of antibiotics Biggest class are the Beta-Lactams This group includes: Penicillins (pen, amox, fluclox etc) Cephalosporins (cefalexin, cefuroxime etc) Carbapenems (meropenem) Combinations (tazocin, augmentin) They all target the bacterial cell wall

Beta-Lactams The most widely used group of antibiotics Some are very broad spectrum (carbapenem) others much less so (penicillin) Many predispose to C.difficile and colonisation with resistant bacteria (and candida) Many people report “allergies” to this group particularly the penicillins MRSA resistant to ALL Beta lactams

Penicillins Amoxicillin (all routes) Flucloxacillin (all routes) Same spectrum as benzyl pen plus active against enterococci and H.influenzae When first introduced good activity against enterobacteriaceae, most are now resistant by -lactamase production Flucloxacillin (all routes) Primarily anti-staphylococcal agent because of stability to penicillinase. Introduction of amino grpup in alpha position of the side chain of ben pen confers high degree of acid stability together with enhanced activity against gram neg bact

-lactamase Inhibitors Eg clavulanate, tazobactam Main mechanism of bacterial resistance is beta-lactamase production (many types) Can overcome some of this by combining a penicillin with a beta-lactamase inhibitor eg co-amoxiclav, tazocintm Widens spectrum to include staphylococci, some enterobacteriaceae and anaerobes

Antipseudomonal penicillins eg ticarcillin, piperacillin IV only Susceptible to -lactamases so usually combined with a -lactamase inhibitor eg clavulanic acid or tazobactam Trade names – Timentin or Tazocin

Monobactams Aztreonam Only active against Gram negative bacilli including pseudomonas Generally regarded as not so active against anaerobes Generally regarded as “safer for C.diff” Narrow spectrum of activity.

Carbapenems Imipenem, Meropenem, Ertapenem Very broad spectrum, reserved for severe hospital acquired infections Expensive Imipenem contraindicated in CNS disorders Can predispose to C.diff (v.broad spectrum)

Cephalosporins 1st Generation Eg cefradine/cefalexin/cefazolin Gram pos cover > Gram Neg cover MSSA S Streptococci S Enterococci R Enterobacteriaceae initially S, now many R

Cephalosporins 2nd Generation 3rd Generation Eg cefuroxime As 1st generation against G+ve, but improved activity against enterobacteriaceae (more stable to -lactamases) 3rd Generation Eg cefotaxime, ceftazidime Much less Gram pos cover, “more” gram neg activity. Good CNS penetration (cefotaxime) Good Anti-pseudomonal (ceftazidime)

Glycopeptides Eg vancomycin or teicoplanin Gram +ve agents ONLY IV only and toxic (Vanc) Reserved for serious/resistant gram pos eg MRSA or in multiply allergic patients

Protein Synthesis Inhibitors Chloramphenicol Very broad spectrum except pseudomonas Little used today because of toxicity Idiosyncratic aplastic anaemia Still used topically for eyes Most PO/IV usage in Neurosurgery (STH)

Macrolides Eg erythromycin, clarithromycin Good staph and strep activity Used as an alternative to penicillins in soft tissue and throat infections in allergic patients Active against legionella, chlamydia and mycoplasmas - atypical pneumonias No Gram –ve cover

Lincosamides Eg clindamycin Active against staph, strep and anaerobes first antibiotic to be ass. with C.diff & PMC - usage decreased dramatically good bone concentrations and well absorbed orally

Tetracyclines Broad spectrum and were widely used but resistance developed rapidly and usage declined Used for mild MRSA infections and also useful activity against chlamydias (& malaria)

Aminoglycosides Eg gentamicin, tobramycin Active against enterobacteriaceae, pseudomonas and staphylococci (inc mrsa) Synergy with cell-wall antibiotics against streptococci and enterococci Nephro- and oto-toxic, levels must be monitored carefully More toxic than glycopeptides Mostly inelderly and renal failure patients. Dose related and care must be taken to with dosage and whenever possible treatment should not exceed 7 days.

Fusidic acid Mainly an anti-staphylococcal agent Must not use alone as resistance develops by a single mutation Used in combination for serious Staph infection eg osteomyelitis

Oxazolidinone Inhibitor of bacterial protein synthesis - blocks formation of the initiation complex Active against gram pos only including MRSA and VRE expensive and can cause bone marrow suppression with longer courses (>2wks) Only 1 in this class - Linezolid

Nucleic Acid Quinolones Old: eg nalidixic acid Newer: eg ciprofloxacin used as a urinary tract agent resistance develops very rapidly Newer: eg ciprofloxacin good activity against enterobacteriaceae pseudomonas and staph moderate against strep, Increasing resistance an issue MRSA usually resistant - encourages heavy colonisation Also strong assoc. with C.diff & ESBL’s

Rifampicin Used primarily for TB, but good activity against many genera esp Staph’s Resistance develops rapidly if used on its own, therefore used in combination eg in MRSA infections Sometimes used on own for meningococcal prophylaxis - low number of organisms

Metronidazole Anti-anaerobic Bacteria and protozoa Almost all sensitive, although resistance increasing

Folate Antagonists Broad spectrum sulphonamides - little used in UK now because of toxicity trimethoprim - used for UTIs but resistance steadily increasing combination used for PCP (Septrin)

Treatment UTI Organisms: E coli (& coliforms), Staph saprophyticus, enterococci Antibiotics: trimethoprim, amoxicillin +/- clavulanate, 1st gen cephalosporin if more serious (ie ?bacteraemic) then 2nd/3rd gen cephalosporin or quinolone

Treatment - 2 Respiratory COPD - likely organisms: H. influenzae, pneumococcus, Moraxella catarrhalis antibiotics: amoxicillin +/- clavulanate, tetracycline, trimethoprim Pneumonia - pneumococcus, atypicals antibiotics : ß-lactams + erythromycin

Treatment - 3 Wound likely organisms: Staph aureus, Strep pyogenes, anaerobes antibiotics: flucloxacillin, erythromycin, co-amoxiclav Beware MRSA if inpatient

Misuse of antibiotics Use of broad spectrum agents when narrow spectrum agents are as effective treatment for too long a time treatment by intravenous route when oral therapy is equally effective use of combination agents when one agent would suffice failure to alter therapy when sens available

Misuse 2 Failure to use a dosage appropriate to renal and hepatic function failure to initiate therapy based on local susceptibility of orgs in a unit institution of antibiotics with the “worst” case scenario, ie pseudomonas or MRSA when these orgs are highly unlikely Failure to step down once organism known

Dangers of misuse 1:10 inpatients have ADR to a drug they do not need. Up to 10% potentially harmful drug interactions ADR increases substantially with multiple drug prescribing Errors in prescribing monitoring and administration

Dangers of misuse Superinfection Antibiotic resistance selection Candida Clostridium difficile MRSA (esp after cipro) Antibiotic resistance selection MRSA C.diff Resistant Coliforms

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