Pharmacologic Therapy

Empiric antimicrobial therapy should target likely causative pathogen(s) based on patient-specific risk factors and route of infection (Table 81—1). Empiric antimicrobial coverage against S. aureus should be considered for all classifications of osteomyelitis. Specific recommendations may vary based on factors such as patient allergies, potential for harboring a resistant organism, institution formulary, and cost considerations. Antimicrobial therapy should be modified based on culture and sens-

itivity data of appropriately collected specimens (Table 81-2).

Typically, treatment is initiated with IV antimicrobials to ensure that therapeutic drug concentrations will be achieved in the bone.26 IV therapy can be administered in the inpatient or outpatient setting 25,28 Following 1 to 2 weeks of IV therapy, a switch to oral antibiotics may be considered in patients with good adherence and outpatient follow-up 22,25,29 Oral agents should possess such characteristics as high bioavailability, good bone penetration, and long half-life (i.e., extended dosing interval).26,29

Antimicrobials commonly used as oral therapy for osteomyelitis include fluoroquino-

lones, clindamycin, linezolid, and trimethoprim-sulfamethox azole. >>>>>>

Additionally, oral rifampin may be used in combination with another antibiotic in the

25 29

treatment of chronic osteomyelitis, particularly in patients with foreign devices.

Table 81-2 Pathogen-Targeted Antimicrobial Therapy and Dosing Recommendations in Pediatric and Adult Patients

Microorganism

Recommended Therapy

Alternatives

Sfdpii ylotexcui dcjffurj

Mfi&A

MRiA

Vancomycin MC k?ss thJci t*ttti*slK>l nrxg/nil (&7pmol/1)

fniirocmrcui spp.

AmpicilUYsensui-.**

Antivuphylococcal penicillin:

Nafcltlift'/iMX JTUJ :

Pediatric*: IOO-.JOO ing/lo^'day W in drvidfd doses every

Fist geneidlon tephakjspoim (ttaiaiiff:

Adult; 1-2 9 (Vivify 0 hOuiS

Pediatric* H-IOQ mg/hy/Uay W in divided tfcnes every

CJ>iv3twtyOn (drftcn ua.tJ in ix'diitric patlcmiof stfkjus MKSA

infe<lic«5; p?i taim P-(txonlimn iuiiepiiOilily) Pediatric^ ii-AQ mgykgAiay IV In divtded doses every (> Sixxifii ii-JO ririg/ky/u^ordain dividediJcMS-evefy hours Vant&jycln:

Mttdy SUtt lec^jgft 1 i-20 HKq/lmL (10-11 pmoHJ ftdiifl: li-JD mgrtog per dtw IV eveiy 3-1J haws PtHjLJirk.* 10 i[>m«^i3ef(k3W iV'eviiiythCiiis [Visage should he upon actual hctty vveighr Constfcr allcrnallvo agcfll: itfMSiW

Adult: 600 my IWaal every U hours

Pediatric*: 10 rrnj.'k] per dose IVjtoral every 4 hours DDfiKanyHia

Adult: Cj mg/bg IV every 24 hours

A/ripJtMrf: AOull; 2 0IV Ovfly hct*s IVdmlrE". IOO-MO mg/kg/day IV In divided doses Miy J-i hous

& Laclam altagy: vancomycin or c-'-ndamwrm jl-t.irtain allfHOy: wsntomji in

Ampidllin resiilam VforxontyTirvne^iEitant StieptQCQitus spp.

Enlc'DbulcivdK

Itontlnuedi

P\ructvmann\OrruQlnOtO

Anaerobes

ItincDiTytin UuwnAd (jrA^jraniiin PenicHNn Q: AJulL 2-4 inillio'i uniCi IV evoiy A-t> hauri PlhJiJIit6: 250000-40CUOOO Urtili/hjAdiy IV In diwitJo;! dcscscvcry 4-6 fKXift Tliiid Oi fOurlhijeritrSLiW<.e|JtiJklif>Jril> {.ettfiwone-Adull: 1-2 g IV evEry 24 hour* RedBflflrt 50-75 rtig/kg per doss IVevCiy 24 hours CeibfiyirtK"1'; Adufr i -1 q iv every 8 hours Pcdi.il it". 50-200 mgrtujAJay IV in drvidixJ dm« every IS hour* Cfiftlfxfiro?:

AduTl: 1-2 g IV every a liuuri FodiiTit0:100-150 mij/kiyiday iv in divided dos« evinyS hours iifoiirTie'-Adutt 1-2 ij IV every g-12 hci>rs Pednlit1': 50 irnj/kj pel [SowlV every £1-1? hours flpffsri'.'.'.T/iajDiorinm

AduM^TSglVtveiyJl 6 hours Or J.J g IV every G-fi hours FluomxiuiriiJone'.; Cipro floKJiirf

AduJl. 400 mn IVevpiy 12 hctws; 500-750 mi>arfl1 twice ctoily

IrtDrtcmKirr;

Adull: 500-750 mg Moral ones dily MMffiMadf* Adull: 400 my IVtoal onto daily AnrimeudomtX^I (ijHukMpoi (rt Ceitojid/me Ce/epime

M^HdbiffinriitaMifiriHibnf quAtuli iiroftjHJtin CJintinrajfjji':

AJufl: 600 <)00 mg IV evety B hcursi 300- J50 ring CM^il h-K hoin

PsnciUMrit*- ttefei (0 wfijA dosj^e retommeiidartoris Ueliorvtla^ole * Adufl: nK] IWaal pveiy A hons Pfdijlric*- 30 mg/lij/djy IVrtxi In rfcridrrd ttairn.'viCfy fc-li hour*

Latum allergy

CJiUipiiX'nii: im^jfriiin/t ilistwnf: Adull: 500 rug IV every G-S hours tatanin* 60-100 m^/ig/Jiiy ill divided dOS« tviiy 6 hctiii

Adui'. I g tV every LJ houn Pedant* 60-130 mg/kgiday in divided doses every $ hour* Dorpenim1

AduH: 500rny IVeveiy 8 huuii t'ri^piriiijfr Mufc 1 <5 iVt^ery 74 hctus

I""-; h -i.k illii iA.i/oIlk r.irn CiibaptT!omi{onl/ imiwncm/ li tHiai in. moroptneiiv 01

(HeST, <1iil<. difftiJon ipm. MIC, minimum inhibitory ccuvw^rjiio<v MRiA. imeihicilifiieii-irim 1 AiWUfc M$SA, meirvi' n-fenjitbe S dure»!,

"Oosa^e itHuitmem neceiwry In pji ief^i iwilh concomlBrn ienal in(l Hefwrt dyvfurK (ion.

■Hi'fer k> sp^fi-tliTod fljivii/icrrf irtY-riwe im m.ULiiniirn pediatric fliie iVyi rKnri.ii.il rrvdhinn'rKln fcjns jixl dtrfir*}

■Dosage fcljuslmenr neiessaiy renal dysfmirkm.

i&jSitje necessary in severe he[Hlk d^MxiiOii

■FbcioqtfnolaiK NO< ipjuorfrt ttythtUi I llAiar 114ln<HildlHie«oep( ior .i:ml".i* ^mftiig^ li^A^arirdandcnmfiliraml IJllarul pydanephi'l^ (t iprcflosacmi.

Flam POfi. 2.3, 7,4 10-li ?3i,27, 30-S2, M it 36-41,

With increasing methicillin resistance, clinicians will need to be aware of changing treatment strategies for infections that are often staphylococcal in origin. Historically, IV vancomycin has been first-line therapy for serious MRSA infections. Based upon pharmacokinetic/pharmacodynamic principles, higher vancomycin trough levels (15-20 mcg/mL; 10-14 umol/L) have been recommended for serious infections including osteomyelitis.31, 2 Although susceptibility of MRSA to vancomycin remains almost 100%,3 vancomycin displays reduced activity against MRSA with minimum inhibitory concentrations (MICs) at the high end of the susceptible range (MIC 1-2 mcg/mL [0.7-1.4 ^mol/L]).32-37 As a result, clinicians should know the specific MIC of vancomycin for MRSA. If the MIC is greater than or equal to 2 mcg/

mL (1.4 ^mol/L), switching to another anti-MRSA agent may be advisable, despite

lack of FDA approval. Clinical effectiveness has been reported with linezolid and daptomycin in several small, nonrandomized studies against MRSA osteomyelitis (Table 81-3).39-41 However, some in vitro studies have shown reduced susceptibility to daptomycin in vancomycin-intermediate or -resistant S. aureus strains;42- 4 therefore, daptomycin susceptibility should be established prior to switching from van-comycin to daptomycin. Clinical trials being conducted with newer agents include daptomycin versus vancomycin for treatment of osteomyelitis related to prosthetic infections, and tigecycline versus ertapenem for treatment of diabetic foot infections.45 In children, clindamycin is an effective antibiotic against susceptible strains of MRSA.10,30 However, micro-biology laboratories must screen with a disk diffusion test (D-test) for inducible resistance via the macrolide-lincosamide-streptogram-in (MLS) gene as clindamycin failures have been associated with infections caused by these isolates.10,30 Oral anti-MRSA agents often utilized for treatment of osteomyelitis include linezolid, trimethoprim-sulfamethoxazole and clindamycin (mostly in pediatrics).27,29,30

© The duration of treatment is typically 4 to 6 weeks for acute osteomyelitis.25 Chronic osteomyelitis also requires 4 to 6 weeks of therapy. In patients who have undergone surgical intervention, the total length of therapy should be counted after the last major surgical intervention.25 Therapy should be continued until the infection has resolved. Prolonged therapy may be necessary for certain populations such as patients with vascular insufficiency or patients with recalcitrant infections that do not respond to 4 to 6 weeks of therapy.2,4,7,26

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