ANTIBIOTIC THERAPY FOR GPs AN UPDATE

Dr Ross Bradbury

Often community acquired Meth R

pen R fus S rif S tet S gent S

ery S = clind S but many ery R= clind R clindamycin resistance increasing esp. Dubbo

Non multiresistant MRSA

Swab- Staphylococcus aureus PEN R METH R (FLU,DICLOX) CEP R ERY S (= CLIND S ) TET S COT S GENT S

Culture

Swab- Staphylococcus aureus

PEN R

METH R (FLU,DICLOX) VANC S

CEP R FUS S

ERY S (= CLIND S ) RIF S

TET S

COT S

GENT S

Australian Hospital MRSA (since late 1960s)

PEN R GENT R

METH R ( FLU, DICLOX) VANC S

CEP R FUS S

ERY R (= CLIND R ) RIF S

TET R

COT R

MRSA In Australia

life threatening and serious infections

skin, genital, blood; young children

antibiotic resistant

will not respond to β-lactams

48 hrs to get answer back from lab

poor prognosis if delayed antibiotic

other antibiotic choices now; but the future?

Why does CA-MRSA matter?

Boils, furuncles - especially recurrent

Colonisation with pathogenic strains

Now have to consider non-multiresistant

or "CA-MRSA" (Community Acquired)

MRSA

Need culture, sensitivities

Can no longer just prescribe “Keflex”

Cephalosporins drive community resistance

STAPHYLOCOCCAL INFECTION

mec A ccr

Type IV SCC mec CA-MRSA:

Type I SCC mec Hospital –acquired MRSA

mec A ccr

Non-ß-lactamase antibiotic & heavy metal resistance genes

PVL

MMRW 1999;48:707-710

Minnesota & North Dakota, USA • 4 deaths in children with CA-MRSA infections, 2 with

necrotising pneumonia

Dufour et al. Clin Infect Dis 2002;35:819-824

France.

• 14 cases. 2 with fatal necrotising pneumonia Nimmo et al. MJA 2003;178:245

Queensland • 2 patients with necrotising pneumonia complicating CA-MRSA bacteraemia

PANTON-VALENTINE LEUKOCIDIN

FOR MSSA i.e. methicillin (flucloxacillin) sensitive

choice - flucloxacillin oral, or IV - dicloxacillin oral, NOT IV but for moderate to serious infection OR cephalothin/cephazolin clindamycin(if erythromycin S) fusidic acid + rifampicin OR cephalexin, cotrimoxazole OR ciprofloxacin, moxifloxacin OR erythromycin

STAPHYLOCOCCAL INFECTION TREATMENT

FOR CA – MRSA i.e. non-multiresistant MRSA clindamycin 300mg -450 mg tds ( IVI 600mg 8hrly ) If resistant to clindamycin ( = erythromycin resistant) fusidic acid 500mg bd with rifampicin 300mg bd OR co-trimoxazole one bd (Bactrim, Septrin) Or doxycycline 100mg bd OR IV vancomycin (trough levels desirably at 20mg/L ) OR moxifloxacin 400mg daily(nonPBS) OR ciprofloxacin 500mg bd OR linezolid 600mg bd (non PBS) tigecycline

STAPHYLOCOCCAL INFECTION TREATMENT

MRSA - older hospital strain

fusidic acid with rifampicin

IV vancomycin bd OR teicoplanin 400 - 800mg daily

Oral linezolid 600mg bd OR IV 600mg 12 hrly

daptomycin

ceftaroline – new drug – 600mg 12 hrly

tigecycline

STAPHYLOCOCCAL INFECTION TREATMENT

treatment length

Intravenous +/- oral

Septicaemia 14 days

Vertebral osteomyelitis 4-6 weeks + 3 months

Endocarditis 6 weeks

Septic arthritis1 2-4 weeks + 6-8 weeks

Perinephric/splenic abscess1 2-4 weeks + 2-4 weeks

Necrotising pneumonia 4 weeks + 2-4 weeks

Empyema1 4 weeks + 2-4 weeks

Serious Invasive Staphylococcal Infection

1. Will need drainage too

(L) thigh aspirate

Blood (2/2 bottles) MRSA

Sputum

CULTURES

ALL

(R) methicillin, cephazolin

(S) vancomycin, rifampicin, fusidic acid

erythromycin, ciprofloxacin,

gentamicin, tetracycline,

trimethoprim

• Pathogens –ability to invade and damage tissues and cells,usually by excreting toxins

• Isolation of potential pathogens from swab

• Most likely pathogens(always important if isolated) are :

Group A or G beta haemolytic streptococcus

Staphylococcus aureus

Group B beta haemolytic streptococcus

Wound Pathogens

• Anaerobes eg Clostridium perfringens Bacteroides fragilis, Peptostreptococcus

• Group of uncommon pathogens Pasteurella multocida Erysipelothrix rhusiopathiae Corynebacterium minutissimum Corynebacterium diphtheriae Vibrio vulnificus;Aeromonas

Wound Pathogens

• With all of these pathogenic bacteria we would be tempted to treat with systemic antibiotics

• Especially if there was:

- spreading erythema

- pus generation

- pain

- swelling

- heat

Wound Pathogens

E. coli , Klebsiella, Enterobacter

Proteus , Morganella – very unlikely pathogens

Pseudomonas – chronic ulcers, skin graft infections,

burns

MORE DOUBTFUL PATHOGENICITY

organism antibiotic MIC MIC

plankton biofilm

S.aureus vancomycin 2 20

Ps.aerugin. imipenem 1 >1024

E.coli ampicillin 2 512

Burk.pseud. ceftazidime 8 800

Strep.sanguis doxycycline 0.063 3.15

Susceptibility of planktonic and biofilm bacteria to antibiotics

Case History

Blood cultures taken: Grp A Strep

Admitted under ID

iv cefazolin 1g tds

Sc clexane 40mg daily

Regular paracetamol, prn endone

Case History

• Staphylococcus aureus, Group B beta haemolytic streptococcus, anaerobes, gram negatives including Pseudomonas

• Typical antibiotics used:

-IV Timentin ( ticarcillin/clavulanate)

or - IV Tazocin ( piperacillin/tazobactam ) ;

-IV flucloxacillin with metronidazole and initial dose of gentamicin

-oral ciprofloxacin with clindamycin

or -oral amoxycillin/clavulanate(Augmentin)

• Peripheral vascular infections similar

Antibiotics in Diabetic Foot Infections

Aerobes Anaerobes

Cat: Pasteurella multocida Fusobacterium sp

Staphylococcus sp Bacteroides sp

Dog: Pasteurella multocida Fusobacterium sp

Staphylococcus sp Bacteroides sp

Capnocytophaga

ANIMAL BITES

Flucloxacillin : hepatitis; nausea;neutropenia

Clindamycin : diarrhoea(C. difficile)

Fusidic acid : nausea,hepatitis(SAP often raised)

Rifampicin: hepatitis,nausea

Cephalothin: interstitial nephritis

Ciprofloxacin,moxifloxacin:tendon damage

ADVERSE REACTIONS TO ANTIBIOTICS

Cholestatic hepatitis

Australia 1993, 1994 - 7/100,000 first time users

UK 2005 – 8.5/100,000 users

Risk factors –age over 55

-- female sex

--treatment> 14 days

Delayed onset reports - up to 60 days post therapy

Contrast use in UK with Australian experience

FLUCLOXACILLIN

NSW TAG ( Therapeutic Assessment Group ) May 2000

can use either/both in moderate to severe infection

Use flucloxacillin intravenously

Dicloxacillin thrombophlebitis

Do not use either if cholestatic hepatitis or interstitial nephritis with either

Safe in children

FLUCLOXACILLIN/ DICLOXACILLIN

Initially all enzymes rise

AST AST

ALT then ALT

ALP

and ALP i.e cholestatic

pattern

Pattern of Hepatitis with Flucloxacillin Hepatotoxicity

Interstitial nephritis ( silent )

Neutropaenia esp. in high dose

Penicillin allergy

Nausea, vomiting with oral capsules

Baseline EUC, LFTs then repeat if prolonged antibiotics

FLUCLOXACILLIN

Cholestatic hepatitis

Often delayed onset ( mean 17 days)

Mild to life threatening (transplants, deaths)

Fevers, nausea can be associated

AMOXYCILLIN /CLAVULANATE

Clostridium difficile colitis

Skin rashes incl. Stevens Johnson syndrome, erythema multiforma , maculo-papular rash

Cardiac arrest

Warfarin interaction

Hepatitis

Polyarthropathy, myositis

CLINDAMYCIN

2 weeks of triclosan body wash e.g.”Phisohex”

2 weeks of mupirocin nasal ointment

2 weeks of mupirocin ointment(“Bactroban”)

In the first week rifampicin 600mg morning

with flucloxacillin 500mg 4/day

Repeat all this at 2 months

RECURRENT BOILS

Oxazolidinone

600 mg(IV/PO)b.d.

Liver metabolized,no adjustment renal failure

MRSA,MRSE,VRE are covered

Adverse reactions :interacts-tyramine,SSRI’S;thrombocytopenia,

anaemia,leucopenia

Linezolid

ANTIBIOTICS FOR URINARY INFECTIONS

Lower tract infection cotrimoxazole used to be “gold standard” NOW –trimethoprim e.g.”Triprim” less relapses(10% at 4 weeks) resistance increasing-20-40% OTHERS –norfloxacin -amoxycillin/clavulanate - ciprofloxacin (Pseudomonas,Enterobacter) -nitrofurantoin

ANTIBIOTIC USE INCREASED RESISTANCE

• Data from 28 countries – 1173 hospitals – 658 laboratories (60-70%: denominator data)

• ECDC-led (http://www.ecdc.europa.eu/en/)

• Annual report

European Antimicrobial Resistance Surveillance Network

(EARSNet)

National Antibiotic Use - Europe

MRSA

ANTIBIOTIC USE INCREASED RESISTANCE

EARSNet 2010 Annual Report

EC: 3CP

EARSNet 2010 Annual Report

EC: FQs

EARSNet 2010 Annual Report

Streptococcus pneumoniae penicillin “resistance”

Miyakis ClD 11;53:177

WHAT ABOUT ASIA/PACIFIC?

NORTH AMERICA?

SOUTH AMERICA?

Drug Usage Subcommittee of PBAC

-includes all PBS community prescribing and outpatient hospital prescriptions for 3 states for oral antibiotics

-in 2002

Australia- 21 DDDs / 1000pop / day

France - 32DDDs/1000pop/day

Netherlands- 10DDDs/1000pop/day

COMMUNITY USE OF ANTIBIOTICS

23 Analysed hospitals in Australia(50% tertiary)

916DDDs/1000 OBDs

Denmark

649 DDDs/1000 OBDs

Netherlands

583 DDDs/1000 OBDs

Sweden

589 DDDs/1000 OBDs

HOSPITAL ANTIBIOTIC USE

INCREASING

RESISTANCE

NO NEW

ANTIBIOTICS

UNTREATABLE

INFECTIONS

CALL TO ACTION

NATIONAL - Staph.aureus OK (AGAR funded)

RESISTANCE - Gram negatives NOT OK

SURVEILLANCE - Need CDC equivalent

HOSPITAL

ANTIBIOTIC

STEWARDSHIP

INCREASED ? uti’s aged care

COMMUNITY ? URTI, ulcers,

STEWARDSHIP wounds for GPs

? Educating

community

WHAT ACTION?

INFECTION CONTROL

Molecular understanding improving

New antibiotic development is not happening

Basics Important:

hand washing/handrubs

antibiotic stewardship

antibiotic use auditing

support host defences

isolation and source control

Diagnostics GP Conference

Tuesday 18th March 2014

SYDNEY ADVENTIST HOSPITAL

PRESENTS

SPEAKERS

Dr Ross Bradbury – Antibiotic

Therapy for GPs: An Update

Dr David McHarg – Overview of

PET-CT

Dr Andrew Stuart – MRI Imaging of

Conditions that are Medicare

Eligible for GP Referral

CONVENOR

Dr James Cheatham