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Osteomyelitis (1 of 15)

Osteomyelitis (1 of 15)

Osteomyelitis (1 of 15)

1 Patient presents w/ signs & symptoms suggestive of acute osteomyelitis

2 HISTORY & PHYSICAL EXAM No Are history & physical exam compatible w/ osteomyelitis?

Yes

3 DIAGNOSIS Do imaging exam & No ALTERNATIVE lab tests confirm DIAGNOSIS osteomyelitis?

Yes

A Supportive measures B Pharmacological  erapy IV/PO for Empiric  erapy Any of the following: • • • • Other Beta-lactams • Quinolones • • Other antibiotics Local  erapy Suppressive Antibiotic  erapy C Surgery

EVALUATION © MIMSSee next page

Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS.

B278 © MIMS 2019 • • • • • • • • • • • • • • Factors Risk • • • • • • &Symptoms Signs • Tobacco consumption >2packs/day Neuropathy Radiation fibrosis disease Peripheral vascular Chronic hypoxia Renal orhepatic impairment Cancer Malnutrition Organ transplantation abuse drug IV Immunosuppression mellitus (DM) Diabetes ageAdvanced orunderlying internal fractures fi underlying open tissuenecrosis, bone, Chronic woundsw/exposed xation malaise vomiting, Anorexia, osteomyelitis involved over vertebrae &tenderness inpatients w/vertebral abdomen orleg, back, Pain inthe chest, movement ofaffLimited extremity ected affDraining sinus over tracts bone ected Infl fiammatory the over warmth, pain,&swelling involved area oferythema, ndings Fever - may occur also infections isgenerally Infection butpolymicrobial duetoasinglemicroorganism - ortrauma surgery from into inoculation ordirect bone tobone, &joints tissues contiguousspread, soft from spread Osteomyelitis isanacuteorchronic infl hematogenous from resulting ammation duetoaninfection ofthe bone

© MIMS& adults aureus isthe common most ofacuteorchronicStaphylococcus cause hematogenous osteomyelitis inchildren Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing TREATMENT OSTEOMYELITIS FOR • • • is improving &cultures are negative Continue empiric treatment ifpatient therapy, when feasible suitability foroutpatientAssess results culture &sensitivity on May change antibiotics based 1 Is patient responding wellto Is patient responding CONTINUE TREATMENTCONTINUE PATIENT UNDERGOING treatment based on clinical onclinical based treatment CLINICAL PRESENTATION Osteomyelitis (2of15) & lab parameters? & lab EVALUATION Yes 4 B279 No • • • REASSESS PATIENTREASSESS out malignancy torule May dobiopsy forsurgery need Assess necessary Change antibiotics as © MIMS 2019

OSTEOMYELITIS OSTEOMYELITIS • • • • • Diagnoses Alternative • • • • • Osteomyelitis Chronic • • Osteomyelitis Nonhematogenous Contiguous • • • • AHO Classifi Adults in ofOsteomyelitis cation • • • Osteomyelitis Nonhematogenous Contiguous • • • • • • • • (AHO) Hematogenous Osteomyelitis Acute Classifi Children in ofOsteomyelitis cation • • • • Findings Exam Physical (eg etc) factors vasculopathy, Elicitpredisposing procedures, invasive DM, History: Bone malignancy Bone hemoglobinopathy disorders eg inpatients esp infarction w/blood Bone Fracture, gout &bursitis &Charcot ofbone) arthropathy necrosis (avascular Osteonecrosis tissueinfection Soft Hematogenous osteomyelitis may chronic &contiguous-focus become obstructed ifasinus found,esp may tractbecomes be tissueinfection An abscess orsoft cells plasma histiocytes, w/lymphocytes, leukocytes (involucrum) &exudation ofpolymorphonuclear bone formation ofnew hardware, chronic afracture woundover orsurgical bone, Pathologic exposed features include bone, presence ofnecrotic asinus tractispathognomonic fever; low-grade erythema, ofosteomyelitis iepain,swelling, w/recurrence ofsymptoms inpatients w/ahistory Diagnosed formation sequestra after infection Bone - Diabetic patients often develop osteomyelitis even before bone isexposed bone before osteomyelitis even patients develop Diabetic often - space toenail, infection ordeep aningrown ulcers, foot include perforating events Predisposing - contribute also Neuropathy tothe function neutrophil risk &diminished - insuffivascular ciency that ofimpairment of isaresult Patients oftissueperfusion are toosteomyelitis w/DM susceptible because trauma tissue infections, &internal reduction fi surgical needing w/fractures Associated soft prostheticdevices, fractures, xation, open -  elumbar&thoracic commonly spineare most aff- ected wktomth over progresses slowly Condition - Vertebral w/incidence w/age increasing ofadults, osteomyelitis ispredominantly adisease infection hematogenous osteomyelitis ismore ofachildhood common &isusuallyareactivation Secondary inadults inthe diaphysis usuallystart Infections usuallypresentAdults inachronic manner, mth several w/pain&minimalconstitutional lasting symptoms ahighrate of recurrenceHas anindolent &w/continuous as conditionPresents w/ofever often drainage orulceration the over aff bone ected puncture orknee ofthe woundsesp foot human &animalbites, &neuropathic decubitus ulcers, devices, orthopedic reduction, surgical requiring fractures w/open Associated abnormality orhippain gait as involved &usuallypresents the often are ilium&ischium most In patientsosteomyelitis, w/pelvic ofthe involves endplates infection of2adjacent Often vertebrae - septicemia eg symptoms Vertebral osteomyelitis isuncommon anindolent w/nonspecifi inchildren as infection presents &often c more diff tends tobe ininfants Infection are anatomic notable barriers toeffi because use ciently limitinfection tissuemay occur into formationAbscess &extension soft surrounding ofinfection involvementMultiple bone iscommon ininfants - inthe metaphysis inchildren frequently are most infections localizing involved, w/most bones Long <2wk patients lasting present Most w/symptoms w/AHO - &children occurs mainlyininfants AHO Primary (dead bone) formation ofsequestra before infection Bone ofsepticemia Signs anulcer toexamine encounters used oraprobe onulcer bone bone bed Exposed Tissue ulceration the &drainingsinus over aff tracts bone ected Tenderness tissuefi tosoft disproportionate tissueinfection favors osteomyelitis soft over ndings - Warmth, the over &tenderness involved part erythema

Infection may spread from skin & soft tissue, respiratory & genitourinary tract, infected IV sites, endocarditis sites, IV infected tract, &genitourinary tissue,respiratory may skin&soft from spread Infection proximal femur &proximalradius, humerus frequentlyMost aff distal the by distalhumerus, are the sites distalfemur followed &proximalected tibia, - Positive palpation of bone in probing an infected foot ulcer foot confi Positive inprobing palpation aninfected ofbone - osteomyelitis rms © MIMS 2 HISTORY & PHYSICAL EXAM Osteomyelitis (3of15) B280 © MIMS 2019 • • • • • X-raysPlain exams Imaging • Techniques Imaging Other • • • • Scan Bone • • • • • (MRI) Imaging Resonance Magnetic • • • • • • (PCR) Reaction Chain Polymerase • • • • Biopsy Bone • • • TestsBlood • • • • Culture Bacterial Exams Lab • - In children, onset w/in3days ofsymptom changes early seen may be apparent tobecome lesion to 21days forabone achange tooccur before onplainx-ray therefore, 30-75%needs demineralization by isseen; 10 ittakes Bone Positive x-rays specifi are fairly outthe disease torule used x-raysc forosteomyelitis (75-83%),butnegative be cannot forother clues provide conditions &can that forexcludingUseful present may other be diseases First inthe procedure imaging work osteomyelitis upofpatients w/possible - Radionuclide studies inother conditions positive malignancy, infarction May eg be fracture, bone Limitation: orischemia may thrombosis that produced indicate more scan infection aggressive has uptake onbone Decreased involvement forpatients bone Useful inwhommultifocal issuspected radiographs &therefore osteomyelitis earlier start than plain symptoms detect hr after can 24-48 positive May be already implants metal artifacts may produce focal exams; forwhole-body Notrecommended Limitations: management inplanningsurgical Helpful iedrainage &debridement vertebral osteomyelitis early Able todetect abscesses intraosseous &forevaluating patients osteomyelitis, w/established fordiffUseful forconfi tissueinfection, erentiating soft from infection bone therming extent in ofinfection ulcers ofchoice test foot fordiabetic osteomyelitis, fordetecting Highly sensitive are initialradiographs normal &whose resolve woundsthat patients foot donot inDM whohave infected intervals at 2-wk repeated shouldbe Radiographs formation at thebone anterior ofthe edge vertebral disk & new Findings invertebral disk of space,the destruction osteomyelitis intervetebral include bone narrowing involucrum, sequestration tion, singleormultiple abscesses, forma- bone new periosteal elevation, periosteal cortical lucency, changes lysis, Later include bone osteopenia, inadults tissuechanges are harder todetect Soft - - scan tomographyComputed (CT) - - Ultrasound - Helpful in establishing etiology of osteomyelitis when blood & bone cultures are negative &bone ofosteomyelitis when blood inestablishing etiology Helpful stain &culture forhistopath obtained &forGram 2samples shouldbe &at least biopsy than isbetter needle biopsy Open cultures are inthis usuallysterile situation blood vertebral osteomyelitis because Frequently todiagnose needed imaging ofosteomyelitis ifthe isstillindoubtafter Recommended diagnosis the reference ofosteomyelitis standard fordiagnosis samples w/ fiisolating bacteria biopsy Bone & infl of osteonecrosis histologically ndings are disease ammatory ofsequelae greater risk apossibly predicting w/higher levels iselevated, level C-reactive protein (CRP) therapy during guide at &may aprognostic sedimentation the rate provide onset (ESR) isusuallyelevated Erythrocyte osteomyelitis count inacutehematogenous highornormal mayWBC inchronic be osteomyelitis &isusuallynormal smear,Gram-stained aerobic &anaerobic performed cultures shouldbe pathogens Sinus tractcultures are reliable forconfi gram-negative fordetecting butare Saureus notuseful rming infection &joint fl bone Blood, the ofthe yield test toincrease cultured allbe uid shouldideally isextremely microorganism osteomyelitisIsolation ofthe infecting of longbone important forthe diagnosis Highlyaccurate forconfi orexcludingrming ofchronic the diagnosis osteomyelitis - intracellular that &infl glucosemetabolism increased occurs ininfection Detects ammation - Positron emission tomography &singlephotonemission computed tomography ortherapeutic drainage, ortissuebiopsy diagnostic aspiration toguide used May be -

by muscle swelling & loss; tissue planes normally seen around aff seen normally tissueplanes muscleby &loss; swelling bone ected followed inchildren the may 1stsign inthe tissueswelling region be &infants, metaphyseal soft Focal deep the extent of bone & soft tissueinflthe extent &soft ofbone ammation but may more information about provide osteomyelitis, ofpossible Not routinely forevaluation required column & for guiding biopsies & aspiration procedures &aspiration column biopsies &forguiding fordefiUseful ofcomplex inareas esp anatomy tissueinfection thening the eg vertebral extent &soft ofbone than doingeither alone test more may useful be scan cell (WBC) orwhiteblood scan together w/atechnetium obtained scan A gallium © MIMS offl that technique indetection Noninvasive helpful may be tissues insoft orsinusuid collection,tracts abscesses osteomyelitis w/ possible patients routinely forevaluating used &shouldnotbe sequestra except than sensitive MRI Less fordetecting Osteomyelitis (4of15) 3 DIAGNOSIS B281 © MIMS 2019

OSTEOMYELITIS OSTEOMYELITIS • AHO Common Pathogens Osteomyelitis in • • • • • • • therapy forempiric anantibiotic Factors toconsiderwhenchoosing • • • • • • • • Vertebral Osteomyelitis • • • Osteomyelitis Contiguous-Infection • • • - S aureus agent isthe common most etiologic inchildren &adults Antibiotic &effi safety cacy Underlying co-morbid conditions Current stainresults Gram ofrecent antibioticHistory intake ofinfection Severity Age ofpatient children esp Empiric antibiotic coverage forSaureus isindicated - pathogens &theirSuspected antimicrobial pattern susceptibility chronic osteomyelitis adjunct fortreating auseful may be oxygenHyperbaric therapy pressure woundtherapy &negative (NPWT) Encourage smokingcessation toimprove woundhealing abnormalities metabolic Correct patient’sOptimize status nutritional &vascular medical, , abusers are drug due to Paeruginosa more prone to infections IV instrumentation or tractinfection of recent urinary agent w/ahistory those E coli esp anetiologic may inadults be &x-rays ifsymptoms indicate chronic infection suspected isthe commonSpondylitis most ofMycobacterium form &shouldbe tuberculosis musculoskeletal infection S aureus isthe frequently pathogen most isolated bone fi dental prosthetic devices, infection, or sinusitis, chronic otitismedia human bites, ofthe brous dysplasia Anaerobic organisms are common including in patients surgery, factors w/ risk ulcers, decubitus DM, trauma, bacilli&anaerobes spp, gram-negative Enterococcus spp, staphylococci, &negative Streptococcus commonly most coagulase-positive bone, from isolated insuffiAmong patients whohave vascular generalized ciency, multiple w/DM, those pathogens esp are usually multiple bacilli&anaerobes pathogens including gram-negative isolated may be also insuffiAmong patients vascular w/ogeneralized ciency, but bone, frequently Saureus from ismost isolated diseases indigenous forcertain fungal catheter-related locations orare ingeographic w/chronic those granulomatous disease, fungemia, neutropenia, patients whoare immunocompromisedFungi w/prolonged eg the may ofosteomyelitis inneonates, cause be organisms fungal abusers P. are by drug more Salmonella prone spp toinfections & Saureus, IV marcescens, Serratia aeruginosa, B, anaerobes Haemophilus infl aeruginosa, coli & otherentericEscherichia gram-negative bacilli, Pseudomonas type uenzae Kingella Spyogenes, inchildren kingae pneumoniae, ; rarely, ofAHO includeOther Streptococcus causes - Candida spp Enterobacter spp,orCandida

S aureus (MSSA) w/-sensitive than children forlonger infected periods hospitalized &be have fever prolonged Children are more w/community-acquired likely infection to Methicillin-resistant Saureus (CA-MRSA) © MIMS abscesses intraosseous & are subperiosteal well more likelyChildren infection as as tohave w/MRSA ofinfection multiple foci Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing B PHARMACOLOGICAL THERAPY A SUPPORTIVE MEASURES SUPPORTIVE Osteomyelitis (5of15) B282 S aureus, Serratia Serratia spp, Klebsiella © MIMS spp, 2019 • • • • • • • • • Antibiotics Beta-lactam • • • Combinations Antibacterial • • •  forEmpiric Antibiotics erapy • • • • • Tetracyclines • • Rifampicin • • • • • Quinolones • • • • However, - &anaerobes duetoMSSA tobe forempirical therapy ofosteomyelitis used suspected May be penetration bone good Achieves antibiotics are Kkingae activeagainst beta-lactam Most forresistant isolates used may be orCeftriaxone - iseff Salmonella against ective Pseudomonas by for osteomyelitis caused &/oranaminoglycoside isaneff orCeftazidime orCefepime, , Antipseudomonal combinationective orPhenoxymethylpenicillin agents are forcompleting PO recommended treatment - enterococci S pneumoniae & susceptible ofchoice isthe Astreptococcus, group drug by fortreating osteomyelitis caused agents & are tocomplete PO that treatment used may be - MSSA by caused to be initialchoices forosteomyelitis are suspected good 1st generation & (eg ) cephalosporins therapeutic concentrationsAchieve inbone cephalosporins, Eg penicillins, TMP-SMZ streptococci &enterobacteriaceae activeagainst isalso Eff eff many butstudiesregarding against isolates ective MRSA inosteomyelitis are limited ectiveness &Trimethoprim (SMZ) [Sulfamethoxazole Eg (TM)] Co-trimoxazole response clinical on treatment toPO based later possible step-down may antibiotics areat be given oftherapy; theIV start children therapyEmpirical shouldinclude inboth coverage &adults ofAHO Saureus against However, treatment inanacutely debridement illpatient forbone delayed towait shouldnotbe - forcultures are sent specimens Antibiotic after treatment started shouldbe , Spneumoniae &Ampicillin-resistant ofSpyogenes isolates Active enterococci most against 10-15% resistance ofchoiceDrug toMethicillin &Clindamycin forempiric exceeds therapy where CA-MRSA in areas inpregnant patients avoided Should be ofage>8 yr considered in shouldonlybe in youngchildren use growth; may &tooth instunted result bone Eff eff many butstudiesregarding against isolates ective MRSA inosteomyelitis are limited ectiveness rapidly resistance develops monotherapy as because used be Should never incombination Saureus actionagainst used w/cell-wall antibioticsMay forsynergistic be therapy combined w/anotherShould adequate coverage be antibiotic toachieve Saureusempiric against during anaerobes spp&some have quinolones Streptococcus actionagainst better newer have coverage variable Quinolones ; nocoverage S aureus against &S epidermidis spp; Enterococcus against organisms including enterobacteriaceae gram-negative by totreat osteomyelitis caused used May be Notroutinely inyoung children foruse recommended - oral absorption into penetration &excellent the bone ofgood treatment forPO because ofosteomyelitis inadults used May be Eg Ciprofloxacin &Ofl oxacin ofexcellent therapyAlternative because IV toprolonged oralbioavailability Active streptococci &Vancomycin-resistant against enterococci eff as May be Vancomycin as ective MRSA by caused intreating infections &Spneumoniae ofSpyogenes isolates Active most against Treatment ismore failure likely inthe presence ofinducibleresistance -

inducible -lincosamide- Bresistanceinducible macrolide-lincosamide-streptogramin through the Dtest

© MIMS for tested toClindamycin susceptible S aureus should be isolates butresistant toErythromycin Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not B Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing PHARMACOLOGICAL THERAPY (CONT’D) Osteomyelitis (6of15) B283 © MIMS 2019

OSTEOMYELITIS OSTEOMYELITIS • • • • • • • •  ofAntibiotic Duration erapy • • • •  Antibiotic Suppressive erapy • •  Antibiotic Local erapy - patient’s parenteral inacommunity-based Assess enrolled therapy anti-infective tobe program need empiric antibiotic therapy continued shouldbe areIf cultures resolving, are &symptoms sterile studies ofculture &sensitivity onresults based Antibiotic therapy revised shouldbe 1wk oftreatment the about 2days start after after tonormal peak &return levels CRP - oftreatment the 3-5days start 2wk after inabout levels tonormal &return usuallyreach peak ESR levels - &lab through parameters resolution) totreatment (iesymptom clinical isevaluated Response - Stage 2(superfi superfi requires cial) often - cial debridement, coverage ablation &possibly unroofi requires often Stage 1(medullary) reaming ng &intramedullary - intervention needed ofsurgical the type to guide osteomyelitis is classifiLong-bone stages used may these on the be magnitude of infection; into stagesed based toimprove 48-72hrofantimicrobial &failure after presence bone, therapy ofnecrotic abscess orsinus bacteremia, tractformation, Indications include persistent fever, pain&swelling, erythema, 3-6wk isusuallybetween Range agent onextent etiologic course &clinical ofinfection, Based Treatment duration isusually6mth Choices TMP-SMZ, include Fusidic (combined Rifampicin acid,quinolones, w/other antibiotics) results testing onsensitivity agents based as etiologic active against toxicity antibiotics have &are into &low that adequate penetration good bone, achieve Choose butisnotfeasible forpatientsConsidered treatment inwhomsurgical isneeded therapy, events adverse fewer w/markedly therapy though isassociated local therapy antibiotic systemic over oflocal studies are the available superiority toadequatelyLimited support space fordefia dead whilewaiting nitive management Antibiotic-impregnated (usuallyw/aminoglycosides orVancomycin) placed maytosterilize be beads acrylic - -

interventions, written policies & procedures &outcomes monitoring &procedures policies written interventions, qualifi effi team, health care ed outpatientA functioning parenteral antimicrobial therapy & other testing cient (OPAT) of communication, means for follow-up, guidelines shouldhave program acomplete & grafting debridement, space stabilization &bone dead management, needs temporary often Stage 3(localized) © have ahomeenvironment that issuffiMIMS care cient tosupport A candidate forinclusion inanOPAT toparticipate inthe &should program willing shouldbe program forStage required 3 to procedures Stage 4(diff stabilization w/internal through fi reduction orexternal open needs often use) xation inaddition Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not B Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing PHARMACOLOGICAL THERAPY (CONT’D) Osteomyelitis (7of15) 4 C EVALUATION SURGERY B284 © MIMS 2019 Bekanamycin 3-5 mg/kg/day IM/IV divided 8hrly divided 3-5mg/kg/day IM/IV Tobramycin divided 4-6mg/kg/day IM/IV 12-24hrly 1-2g/day IMdivided Kanamycin 6or divided 3-5mg/kg/day IM/IV Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All

© MIMS 8hrly 2-2.5 mg/kgIM/IV or 6hrly 1.5-1.9mg/kgIM/IV Childn: 8hrly divided 3-5 mg/kg/day IM/IV 8hrly divided 6-7.5mg/kg/day IM/IV Childn: 8 hrly Up divided to7.5mg/kg/day IM/IV 8-12 hrly 12-24hrly divided 30-50mg/kg/day IM Childn: fill cavity to 10-90beads dioxide 20mgbead: 7.5mg/Zirconium Gentamicin 8hrly 2-2.5mg/kgIM/IV Childn: 6or8hrly divided 5mg/kg/day IM/IV dose: Max 8 hrly 12 hrly 10-20mg/day IMdivided Childn: 12 hrly IMdivided8or mg/day 400-600 1.5g/day dose: Max or 24hrly 8,12, divided 15 mg/kg/day IM/IV Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Dosage Guidelines Osteomyelitis (8of15) AMINOGLYCOSIDES B285 • • • Instructions Special • Reactions Adverse gastrointestinal ulcerationgastrointestinal inpatients avoided Should be w/ cochlear impairment Parkinson’s);myasthenia gravis, or vestibular (eg w/muscle weakness associated Use w/caution inpatients w/conditions - Consider monitoring of serum ofserum Consider monitoring - ototoxic/nephrotoxic drugs receiving orhavewho are also other received or orforlongperiods receiving highdoses renal impairment, inpatients whoare w/ dehydrated those in geriatric, patients, &nephrotoxicity likely areOtotoxicity most pain&infl local reactions, ammation hypersensitivity muscular paralysis); & depression inresp resulting blockade neuromuscular eff (neuromuscular ects administered); have been also drugs usuallywhen other nephrotoxic reported been acuterenal has failure nephrotoxicity; vertigo); renal effdizziness, (reversible ects loss, ototoxicity inhearing resulting effOtotoxic (can irreversible cause ects

concentrations/MIC ratio patients inthese concentrations serum &/orpeak Remarks © MIMS 2019

OSTEOMYELITIS OSTEOMYELITIS ( Cephradine) Cefazolin ( Cephalotin) ( ) Cefaloridine ( Cephalexin) 12hrly 24hrly ordivided 1-2gPO Cefalexin (1stGeneration) Cephalosporins (TM)] Trimethoprim & (SMZ) [ Co-trimoxazole Sulfamethoxazole Sulfamethoxazole Drug Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All

divided 6-12hrly divided © 50-100mg/kg/day IV Childn: 8g/day dose: Max 6hrly 1 gIV 6-8hrly divided 25-50mg/kg/day IM/IV Childn: 8-12hrly divided 1-4 g/day IM/IV 4-6 hrly 20-80mg/kg/day divided Childn: 4-6hrly divided 1-6 gIM/IV/day 12hrly divided MIMS 50mg/kg/day IM/IV Childn: 6g/day dose: Max 6-12hrly 0.5-1 gIM/IV 4g/day dose: Max 6-12hrly divided 25-100mg/kg/day PO Childn: 6g/day dose: Max 6-8hrly 250-500 mgPO 12hrly divided 25-50mg/kg/day<40 kg: PO 12hrly divided onTMP based 6 mg/kg/day Childn: 12 hrly 160 mgTM PO 800 mgSMZ/ Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Dosage Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing ANTIBACTERIAL COMBINATIONS Dosage Dosage Guidelines Osteomyelitis (9of15) • • • • Instruction Special • • Reactions Adverse CEPHALOSPORINS consider administration offolinicacid) &w/caution inpatients w/folatedysfunction defi (may ciency Use w/caution inpatients w/renal impairment hepatic orsevere anemia duetofolicaciddefi megaloblastic disorders esp ciency Use w/extreme caution ornotat allinpatients w/hematological in patientsContraindicated allergic tosulfonamides Maintain adequate fluid intake eff occurred has meningitis Aseptic ects; Rarely hepatic eff orw/highdoses; for longperiods renal ects, Rarely hematologic eff which more may common be ifgiven ects Urogenitalsyndrome); eff inthe urine) (crystallization ect threatening(eg tosevere/life (eg rash) Stevens-Johnson range mild from can reactions Hypersensitivity photosensitivity); eff Dermatologic glossitis); /colitis, pruritus, (rash, ects GI eff (N/V, ects rarely antibiotic-associated diarrhea, anorexia, B286 • • • Instructions Special • • • Reactions Adverse impairment Use w/caution inpatients w/renal sensitivity Penicillin, there 10%chance may be ofcross Use w/ caution inpatients allergic to distress gastric todecrease taken w/food May be chain-containing w/ NMTTside frequently most &occur reported have been w/o bleeding) &/orhypoprothrombinemia (w/or (APTT), time thromboplastin partial activated prolonged prothrombinProlonged time(PT), have occurred hematologic eff Hepatic &renal effects; ects (encephalopathy, convulsions); Rarely eff w/CNS associated may be High doses ects eff infections) (Candidal ect diarrhea/colitis); Other antibiotic associated occur); GIeff N/V, (diarrhea, ects rarely can anaphylaxis such reactions as severe rash, pruritus, (urticaria, reactions Hypersensitivity Remarks cephalosporins cephalosporins Remarks © MIMS 2019 / 24hrly 1-4gIV Inhibitor w/Beta-Lactamase (3rdGeneration) 12hrly 2gIV 6-8hrly 1-2gIM/IV Cefotaxime 12hrly 2-8gIM/IV Cefoperazone 6-8hrly 1.5gIV (3rdGeneration) Cephalosporins 6-12hrly divided 1-4g/day IM/IV 12hrly divided 1-2g/day IM/IV 4,6,or8hrly 1-2gIM/IV (2ndGeneration) Cephalosporin Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All

© 80mg/kg/day dose: Sulbactam Max 6-12hrly divided 40-80mg/kg/day IV Childn: 8g/day (4gofCefoperazone) dose: Max 12hrly divided 2-4 g/day IV 24hrly 20-80 mg/kg/day IV 6g/day dose: Max 8-12 hrly 30-100mg/kg/day divided Childn: MIMS 9g/day dose: Max 6-8hrly divided 200mg/kg/day IM/IV dose: Max 6-12hrly divided 50-100mg/kg/day IM/IV Childn: 12g/day dose: Max 300mg/kg/day dose: Max 12hrly divided 50-100mg/kg/day IM/IV Childn: 16g/day dose: Max 8hrly divided 70-150mg/kg/day IV Childn: 6-12hrly divided 40-80mg/kg/day IM/IV Childn: 6-12hrly 20-40mg/kgIM/IV Childn: 12g/day dose: Max 6hrly to3gIM/IV dose May increase 8hrly 1-2 gIM/IV 6-8hrly divided 40-80mg/kg/day IV Childn: 8hrly 200-400 mgPO to4g/day dose May increase 6-12hrly divided 0.5-2 g/day IM/IV to150mg/kg/day dose May increase 6-12hrly divided 25-100mg/kg/day IM/IV Childn: hrly May increasedoseto4g/dayIM/IVdivided6-12 to150mg/kg/day dose May increase 4-8hrly divided 50-100mg/kg/day IM/IV Childn: Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing CEPHALOSPORINS (CONT’D) Dosage Guidelines Osteomyelitis (10of15) Dosage B287 • • • Instructions Special • • • Reactions Adverse renal impairment Use w/ caution inpatients w/ sensitivity 10%chancemay be ofcross allergic toPenicillin, there Use w/caution inpatients distress gastric decrease to taken w/food May be cephalosporins chain-containing frequently side w/NMTT &occur most reported have been w/o bleeding) hypoprothrombinemia (w/or &/or (APTT), time thromboplastin partial activated prolonged (PT), prothrombinProlonged time & renal eff have occurred ects hematologic eff Hepatic ects; convulsions); Rarely (encephalopathy, effw/ CNS ects associated may be High doses infections) (Candidal diarrhea/colitis); Other eff ect antibiotic-associated eff N/V, (diarrhea, ects rarely occur); GI can anaphylaxis such reactions as severe rash, pruritus, (urticaria, reactions Hypersensitivity Remarks © MIMS

2019 OSTEOMYELITIS Levo oxacin B289 L Kanamycin B285 K B289 I Gentamicin B285 B291 Imipenem/Cilastatin B289 Linezolid B292

Sisomicin B285 S Rifampicin B292 R Pe oxacin B289 P O oxacin B289 O Netilmicin B285 N B289 M Sulbactam B287, B288 Penicillin GB288 B288 Oxacillin Metronidazole B292 Penicillin GKB288 Penicillin GNa B288 Penicillin VB288 Penicillin VKB288 B288 B288 Piperacillin/ B288 Piperacillin/tazobactam OSTEOMYELITIS Oxacillin Cloxacillin Antistaphylococcal Penicillins 6-8hrly 2.25-4.5gIV ( /clavulanate) Ticarcillin/ Piperacillin/ tazobactam Piperacillin Inhibitors Penicillins w/orw/oBeta-Lactamase Antipseudomonal w/ adoubleester) chemically are linked drugs Ampicillin/sulbactam, the 2 ( Sultamicillin: of Pro-drug Ampicillin/ sulbactam Ampicillin Amoxicillin/ clavulanate) ( Co-amoxiclav, Amoxicillin/ clavulanic acid 8hrly 250mg-1gPO Amoxicillin ( Amoxycillin) Inhibitors w/orw/oBeta-Lactamase ( Penicillin V, Penicillin VK) Phenoxymethylpenicillin G K) G, ( Benzylpenicillin Penicillin Penicillin G Na, Penicillin GNa, Penicillin Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing divided 6hrly divided 50-100mg/kg/day <40kg: IM/IV Childn 6hrly 500 mg-1gPO 4-6hrly 500 mg-1gIM/IV 6hrly 250-500 mgPO 6-8hrly divided 8 g/day IM/IV 6hrly 125-250mgPO Childn: 6hrly 250-500 mgPO 6hrly 250-500mgPO Childn: 6g/day dose: Max 6hrly 250-500 mgPO 4-6hrly 500 mgIV 250 mgIM4-6hrly 4-6hrly 3.2 gIV 4-6hrly 2-4 gIM/IV 6-8hrly 150mg/kgIM/IV Childn: 4gofSulbactam or16g/day dose: Max 6,8,or12hrly divided 1.5-12 g/day IM/IV 4-6hrly 500 mgIM/IV 8hrly divided 25-50mg/kg/day PO Childn: 6-8hrly 1.2 gIV 12hrly 625 mg-1gPO 6-8hrly divided 25-40 mg/kg/day IM/IV 8hrly divided 25-50 mg/kg/day PO Childn: 6g/day dose: Max 6-8hrly 250-500 mgIM/IV 6hrly divided 50 mg/kg/day PO 0.6-3.6 g/day divided 4-6hrly 0.6-3.6 g/day divided Dosage Guidelines Osteomyelitis (11of15) PENICILLINS Dosage B288 • • Instructions Special • • Reactions Adverse w/ renal impairment Use w/caution inpatients Penicillin allergy Avoid in patients w/ convulsions) eff (encephalopathy,ects w/CNS associated be may highdoses occurred; renal &hepatic eff have ects Rarely hematologic eff ects; eff infections) (Candidal ect diarrhea/colitis); Other antibiotic-associated effects (diarrhea,N/V,rarely occur); GI can anaphylaxis eg reactions severe pruritus, urticaria, (rash, reactions Hypersensitivity Remarks

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MIMS

2019 Tazobactam B288 T Sulfamethoxazole B286 B290 Sulfamethoxazole (SMZ) &Trimethoprim (TM) B286 Tetracycline B290 Sultamicillin B288 Ticarcillin B288 Ticarcillin/clavulanate B288 Ticarcillin/clavulanic acidB288 Tobramycin B285 Trimethoprim B286

Vancomycin B291 V 1-2 g/day IM/IV 8-12hrly 1-2g/day IM/IV Aztreonam Meropenem Cilastatin Imipenem/ Ciprofl oxacin 24hrly 1gIM/IV Carbapenems Pefl oxacin Ofl oxacin Levofl oxacin Drug Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed 50 mg/kg IM/IV 6-8hrly Childn: 50mg/kgIM/IV 6-8hrly IV to2g/day IM/ dose May increase 8hrly 10-20mg/kgIV Childn: 2g/day dose: Max hrly 0.5-1 g/dayIVdivided8-12 2g/day dose: Max 6hrly IV 15mg/kg ≥3mth,<40kg: Childn 4g/day dose: Max 6-8hrly divided 1-2 g/day IV 500-750 mg PO 12hrly 500-750 mgPO 8-12hrly 400 mgIV 1g/day dose: Max 12hrly 15mg/kgIM/IV Childn: 800 mg/day 12hrly or 8 mg/kgIV 24hrly 400 mgPO 12hrly 200 mgIV 12-24hrly 250-500 mgPO 24hrly 500 mgIV & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Dosage OTHER BETA-LACTAMS Dosage Guidelines Osteomyelitis (12of15) QUINOLONES B289 • • Reactions Adverse • • Instructions Special • • Reactions Adverse • • • Instructions Special • Rarely hematologic, hepatic &renalRarely hematologic, eff ects syndrome) life-threatening (eg Stevens-Johnson range mild(eg tosevere/ from rash) photosensitivity); Dermatologic eff ects (rash,pruritus, sleep disorders,restlessness,drowsiness); diarrhea/colitis); CNSeff ects (headache,dizziness, dyspepsia, diarrhea,rarelyantibiotic-associated GI eff (N/V,ects pain, abdominal diarrhea, epilepsy) disorders (eg Use w/caution inpatients w/CNS renal impairment patients w/ orother beta-lactams; cephalosporins Use w/caution inpatients allergic topenicillins, s t c ff e e etc); Rarely syndrome, hepatic Stevens-Johnson (eg reactions dermatologic exfoliative dermatitis, Rarely severe &/orrenallesions dysfunction); ofCNS inpatients esp w/ahistory reported been &convulsions Seizures haveImipenem/cilastatin: effCNS (mental confusion; disturbances, ects Other effoccur; infections) (Candidal ect (eg can anaphylaxis) mild(eg tosevere from rash) ranging reactions Hypersensitivity taste); altered discoloration, tongue/tooth diarrhea/colitis, GI eff N/V, (diarrhea, ects antibiotic-associated hepatic function & in those w/G6PDdefi &inthose hepatic function ciency inpatients w/impaired renal or disorders, CNS of orhistory Use w/ caution inpatients w/epilepsy Avoid tostrong sunlight exposure ortanningbeds orFecontaining orbuff Zn ddIpreparationsered supplements Mg-containing dietary antacids, Al-or hr after or3 hr before 2 Administer at least the QT interval Some havequinolones the potential toprolong Hypersensitivity reactions can can reactions Hypersensitivity Remarks Remarks © MIMS 2019

OSTEOMYELITIS OSTEOMYELITIS Teicoplanin Glycopeptides to 500mgdiluted Fusidate Tetracycline Drug Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed 6-10 mg/kg/day IM/IV dose: Maintenance 12hrly for1st3doses IV 10mg/kg dose: Loading Childn: 400 mg/day IM/IV dose: Maintenance doses 12hrly for1st3 IM/IV 400mg dose: Loading 8hrly 500mgPO 5-12 yr: 8hrly 250mgPO 1-5 yr: susp: Oral for2-4hr infusion IV slow 20mg/kg/day Childn: 500mg12hrly Na fusidate: for2hr infusion IV 250-500 mLslow 6hrly divided PO 20-40mg/kg/day Childn: mg PO500 hrly 12 mg PO250 3-6hrly 24hrly 100 mgPO dose: Maintenance 12 hrly 100mgPO dose: Initial & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Dosage Dosage Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Guidelines Osteomyelitis (13of15) OTHER ANTIBIOTICS TETRACYCLINES • • • • Instructions Special • • Reactions Adverse • Instructions Special • Reactions Adverse • Instructions Special • • Reactions Adverse Use w/caution inrenal orhepatic impairment patients w/SLE Avoid in children &pregnant women; avoid ≤8yr in Periodic monitoring of CBC &LFTs ofCBC Periodic monitoring are advised therapy ifonprolonged function & monitorrenal &auditory Use w/caution inpatients renal dysfunction w/preexisting frequentlybut less than w/Vancomycin than Vancomycin);often eff Ototoxic have occurred ects hepatic eff Renal effects; (renal impairment, butless ects GIeffheadache); (GIdisturbances);ect Hematologic & eff CNS syndrome); Stevens-Johnson (dizziness, ects occur (eg can reactions Other hypersensitivity tolerated than Vancomycin better Generally reported. haveor bronchospasm been anaphylaxis Fever, occasionally pruritus, skinrash, chills, therapysystemic during isrecommended ofhepatic function monitoring Use w/ caution & inpatients w/liver dysfunction dizziness) eff once isdiscontinued);normal drug CNS (headache, ects (jaundice which to &changes returns inliver function GI eff N/V, (anorexia, effects Hepatic dyspepsia); ects Take w/plenty offluid whilesitting orstanding&well - Avoid tosunlight ortanningbeds longexposure have reactions occurred Hypersensitivity disturbances; eff intracranial pressure &visual w/headache ects, hepatotoxicity,Rarely renal dysfunction, hematologic women) inyounginfants/pregnant growth bone discoloration interference ofteeth, w/ infections, (Candidal effDermatologic Other eff (photosensitivity); ect ects when taken w/aninsuffioccurred cient amount ofliqd); ulceration esophageal has dysphagia, colitis occurred, has GI eff (N/V,ects diarrhea/ antibiotic-associated diarrhea,

B290 before retiring tobed retiring before Remarks Remarks © MIMS 2019 Lnoyi 600mgIM12-24hrly Lincomycin 1.2-2.7g/day IM/IV Clindamycin 6hrly 500mgIV Vancomycin (Cont’d)Glycopeptides Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed PO divided 6-8hrly divided PO 30-60mg/kg/day Childn: 6-8hrly 500 mgPO mg IV600 8-12hrly 6-8 hrly 8-25 mg/kg/day PO divided 6-8hrly divided IM/IV 25-40mg/kg/day Childn: 12hrly 300-450 mgPO hrly divided 6-8 12 hrly 6 hrly or 20 mg/kgIV 10mg/kgIV Childn: 12hrly 1 gIV & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Dosage Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing (CONT’D) OTHER ANTIBIOTICS Dosage Guidelines Osteomyelitis (14of15) • • • Instructions Special • • Reactions Adverse • • • • Instructions Special • • Reactions Adverse Discontinue occurs ifdiarrhea hepatic impairment Use w/ caution inatopic patients &inpatients w/renal or colitis of w/history esp Use w/ caution inpatients w/GIdisease (polyarthritis) Hematologic &hepatic eff Other eff have occurred; ects ect multiforme, dermatitis); exfoliative &vesiculobullous eff dermatologic Severe (erythema have occurred ects anaphylaxis) rarely urticaria, (rash, reactions Hypersensitivity taste); N/V, colitis, pseudomembranous pain,metallic abdominal GI eff antibiotic-related severe (diarrhea, ects concentrations serum increased oftheir renal immaturity &potentialbecause tohave Use w/caution inpremature &younginfants neonates function ofauditory monitoring treatment during alongw/ function issuggested avoid renal &renal &otictoxicity, ofCBC monitoring concentrations ofserum Monitoring donetohelp may be the elderly Use w/caution inpatients & w/impaired renal function Avoid ofimpaired hearing in patients w/ahistory treatment) todiscontinue asign as used be &can loss hearing precede tinnitusrenal may impairment, irreversible; may be which is more concentrations likely w/highplasma orin eff Ototoxic factors); w/ predisposing (ototoxicity,ects orinpatients(nephrotoxicity may at occur esp highdoses Hematologic eff Renal have eff occurred; ects ects syndrome); Stevens-Johnson anaphylactoideg reactions, (can reactions range mildtosevere from Hypersensitivity &shock-like occur hypotension also symptoms sometimes torso, face over &upper rash erythema, Flushing, infusion: which rapid isusuallyrelated syndrome” totoo neck “Red B291 Remarks © MIMS 2019

OSTEOMYELITIS OSTEOMYELITIS Rifampicin 450 mg PO 24hrly 450mgPO Rifampicin Rifamycin 12hrly 600mgIV Linezolid Oxazolidinone Metronidazole Derivative Nitroimidazole Drug Products listed above may not be mentioned in the disease management chart but have been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed 600mg/day dose: Max 24 hrly 10mg/kg/day PO Childn: 12hrly 600 mgPO 8-12 hrly  en 7.5mg/kgPO hrly infusion 8-12 1.5mL/kgIV Childn: 8-12hrly infusion 500 mg/100mLIV & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Dosage Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Please see the end of this section for the reference list. reference the for section this of end the see Please (CONT’D) OTHER ANTIBIOTICS Dosage Guidelines Osteomyelitis (15of15) • • Instructions Special • • Reactions Adverse • • Instructions Special • Reactions Adverse • • • Instructions Special • • • Reactions Adverse patients therapy during inthese monitorliver function dysfunction, Use w/ caution inpatients w/pre-existing liver the by CYP450 metabolized acceleratesRifampicin ofdrugs the metabolism etc) ataxia, eff CNS therapy; occur drowsiness, (headache, can ects Renal effoccurred; w/intermittent reported have been ects hepatitis rarelyfunction, occurs); Hematologic eff have ects Rarely hepatic eff (transient inliver abnormalities ects fl Discoloration &body occurred); ofurine has uids diarrhea/colitis antibiotic-associated GIdistress, diarrhea, wellGenerally tolerated; GIeff (N/V,ects anorexia, counts wkly ofblood Recommend monitoring myelosuppression renal & in patients dysfunction w/ severe Use w/caution inpatients w/pre-existing eff infection) (moniliasis ect Other have occurred); thrombocytopenia pancytopenia, anemia, myelosuppression including leucopenia, (abnormal LFTs); Hematologic eff (reversible ects eff Hepatic eff dizziness); insomnia, (headache, ects ect occur); CNS diarrhea/colitis can antibiotic-associated GI eff N/V, (diarrhea, ects constipation, taste, metallic eff forCNS monitoring ects &clinical recommend CBC monitoring >10days, If given Use hepatic impairment w/caution inpatients w/severe When w/alcohol, given adisulfi occur can ram-like reaction neuropathy seizures &epileptiform peripheral caused has use orprolonged High dose reactions hypersensitivity Hematologic &hepatic eff rarely have occurred, ects darkening ofurine) infection, Other eff at doses); high/prolonged occurred (Candidal ects neuropathy peripheral has changes, mood headache, effCNS dizziness, (weakness, reported have been ects GI eff (N/V,ects constipation); diarrhea, taste, metallic B292 Remarks © MIMS 2019

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