The microbiology of chronic osteomyelitis in a developing world setting

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1 SA Orthopaedc Journal Wnter 2017 Vol 16 No 2 Page 39 The mcrobology of chronc osteomyelts n a developng world settng PG Mthethwa MBBCh, H Dploma(Ortho)SA Regstrar, Department of Orthopaedcs, Grey s Hosptal, School of Clncal Medcne, Unversty of KwaZulu-Natal LC Maras MBChB, FC(Ortho)SA, MMed(Ortho), CIME, PhD Tumour, Sepss and Reconstructon Unt, Department of Orthopaedcs, Grey s Hosptal, School of Clncal Medcne, Unversty of KwaZulu-Natal Correspondng author: Dr Phakaman G Mthethwa Tumour, Sepss and Reconstructon Unt Department of Orthopaedc Surgery Grey s Hosptal Nelson R. Mandela School of Medcne Unversty of KwaZulu-Natal Petermartzburg, South Afrca Tel: Emal: phakspg@gmal.com Abstract Objectves: The prmary am of ths study was to dentfy the mcroorgansms that cause chronc osteomyelts n a developng world clncal settng and to characterse the antbotc senstvty profle of these pathogens. Furthermore, we amed to determne whether the causatve organsms vary n relaton to physologcal status of the host, the HIV status of the patent or the cause of the nfecton (post-traumatc, post-operatve and haematogenous). Methods: We performed a retrospectve revew of consecutve adult patents treated curatvely for chronc osteomyelts of long bones, over a two-year perod. Patent charts were revewed and data extracted n respect of patent demographcs, the cause of nfecton, physologcal status of the host n accordance wth the Cerny and Mader classfcaton, HIV status, surgcal treatment strategy and causatve organsm. Results: A total of 108 organsms were dentfed n the 60 patents ncluded n the study. Multple organsm were cultures n 45% of patents, a sngle Gram-postve organsm n 22% and a sngle Gram-negatve organsm n 26% of patents. In four cases (7%) no causatve organsm was cultured. The most prevalent organsms were Enterobacteraceae (34%), Staphylococcus spp. (29%), Pseudomonas aerugnosa (11%), and Enterococcus spp. (9%). Many solates were found to be resstant to commonly used emprcal ant-mcrobal agents. Seventy per cent of Enterobacteraceae spp. were resstant to ether cefuroxme and/or ampclln-clavulanc acd. Seventy-seven per cent of Staphylococcus aureus solates were susceptble to cloxaclln. More than 50% of Pseudomonas aerugnosa strans were resstant to meropenem, mpenem, pperaclln-tazobactam or cefepme. There was a sgnfcant assocaton between the aetology of the nfecton and the mcroorgansms nvolved (p-value < 0.01). The bacteral pathogen profle was, however, not assocated wth the physologcal status of the host (p=0.22) or the HIV status of the patent. Concluson: Whle the majorty of haematogenous chronc osteomyelts stll nvolved a soltary Gram-postve organsm, the ncdence of Gram-negatve nfectons was found to be hgher than prevously reported. Contguous chronc osteomyelts was mostly polymcrobal n nature and soltary nfectons nvolvng a Gramnegatve organsm was most common n the post-traumatc group. The bacteral pathogen dd not vary n relaton to the HIV status of the patent or the physologcal status of the host. Key words: chronc, osteomyelts, mcrobology, antbotcs, treatment, HIV

2 Page 40 SA Orthopaedc Journal Wnter 2017 Vol 16 No 2 Introducton The dagnoss of chronc osteomyelts encompasses a range of bone nfectons resultng from ether haematogenous bacteral seedng or drect spread from a contguous focus. 1 Tradtonally, the clncal entty of chronc osteomyelts has been domnated by haematogenous dsease. Ths form of the dsease s typcally assocated wth a narrow range of causatve organsms. 1 In recent tmes ths category has been supplemented consderably by contguous nfectons whch are caused by a much wder range of mcroorgansms. 2,3 Posttraumatc, post-operatve and mplant-related nfectons are now encountered much more frequently, especally n developed regons. 2,3 Overall, nfectous complcatons can be expected n approxmately 1 5% of nternally fxated closed fractures and n up to 30% of open fractures. 4 Irrespectve of the cause, chronc osteomyelts remans dffcult to treat and treatment falure may occur n more than 10% of cases. 4 Treatment optons for chronc osteomyelts nclude curatve and pallatve management strateges. 5,6 Curatve treatment protocols nvolve a combnaton of thorough debrdement, dead space management, soft tssue reconstructon and adjuvant antbotc therapy n order to acheve remsson of the dsease pror to reconstructon. Pallatve treatment strateges, may be ndcated n compromsed hosts who are not sutable for complex surgery. 5,6 Typcally pallatve treatment nvolves chronc suppressve antbotc therapy. Knowledge of the mcrobology of chronc osteomyelts may gude the selecton of emprc postoperatve or pallatve antbotc therapy. There s lmted data avalable on the spectrum of causatve organsms, especally n contguous chronc osteomyelts. Prevous studes have shown that the most common causatve organsm remans Staphylococcus aureus, followed by Enterobacteraceae. 1-3 Few studes have been performed n the developng world. Furthermore, the varaton of causatve organsm n relaton to the physologcal host status, the HIV status of the patent or the cause of the nfecton has not prevously been reported. The prmary am of ths study was to dentfy the mcroorgansms that cause chronc osteomyelts n the developng world clncal settng. In addton, we amed to characterse the antbotc senstvty profle of these pathogens. Furthermore, we amed to determne whether the causatve organsms vary n relaton to the physologcal status of the host, the HIV status of the patent or the cause of the nfecton (post-traumatc, post-operatve and haematogenous). Methods We retrospectvely revewed a cohort of consecutve patents who underwent surgcal treatment of chronc osteomyelts at our tertary level musculoskeletal tumour and sepss unt over the two-year perod from January 2012 to December Followng ethcal approval, elgble patents were dentfed from a prospectvely gathered database. All patents, 14 years or older, who underwent surgcal treatment for chronc osteomyelts were ncluded n the study. Cases nvolvng tuberculoss or fungal nfecton, as well as cases wth nsuffcent data, were excluded from the study. The patents charts and X-rays were revewed and data extracted n respect of patent demographcs, the cause of nfecton (haematogenous or contguous) and the host classfcaton n accordance wth the Cerny and Mader classfcaton system. 7 The patent s HIV status, the surgcal treatment strategy employed and the causatve organsm, along wth ther antbotc senstvty profles, were also recorded. In all cases, formal tssue bopsy for the purposes of hstology and mcroscopy, culture and senstvty testng was performed at the tme of the ntal debrdement. Antbotc treatment was dscontnued at least seven days pror to tssue samplng. Samples were processed by agtatng them n a sterle glass ball n 10 ml of Peptone water under lamnar flow. Samples were then plated onto blood agar (ncubated aerobcally and anaerobcally) and lysed blood agar (ncubated n ar wth 5% CO2). Extended culture, for a mnmum perod of seven days, was routnely performed. Organsms antmcrobal senstvty was determned by VITEK2 technology whch dentfes the vast majorty of routne organsms (over 300 mcroorgansms). For the purposes of ths study chronc osteomyelts was defned as a bone nfecton charactersed by the presence of ether necrotc bone or an mplant whch may serve as a ndus for boflm formaton and a duraton of at least 6 weeks. 8 Contguous chronc osteomyelts was defned as post-traumatc (followng open fractures) and postoperatve nfectons, as well as bone nfecton resultng from drect spread from an adjacent septc focus or ulceraton. 9 Statstcal analyss was performed usng Stata 13.0 (Stata Corp. College Staton, Texas). Contnuous varables were reported as mean (± SD) or medan (wth nterquartle range) and categorcal varables as number and percentages, unless otherwse stated. The Fsher s exact test was used for categorcal data. All tests were two-sded and the level of sgnfcance was set at p<0.05. Ethcal approval was obtaned from our nsttuton s ethcs revew board pror to commencement of the study (BREC: BE020/14). The study was conducted accordng to the ethcal prncples for medcal research on human subjects as defned by the World Medcal Assocaton Declaraton of Helsnk (amended at the MA General Assembly, Seoul, Oct 2008). Results A total of 60 patents, from the 64 ntally dentfed to meet the ncluson crtera, were ncluded n ths cohort. Of the four patents who were excluded, one was dagnosed wth tuberculoss osteomyelts and one wth a fungal nfecton (Cryptococcus neoformans), and two cases were excluded on the bass of nsuffcent data. The mean age of the remanng 60 patents was 31 years (range years), wth 47 males and 13 females.

3 SA Orthopaedc Journal Wnter 2017 Vol 16 No 2 Page 41 A total number of 108 mcroorgansms were dentfed and multple organsms were cultured n 45% (n=27) of patents, a sngle Gram-postve organsm n 22% and a sngle Gramnegatve organsm n 26% of patents. In four cases (7%) no causatve organsm was cultured. The most common causatve organsms was found to be from the Enterobacteraceae group (Ctrobacter, Enterobacter, Eschercha, Klebsella, Morganella, Pantoea, Proteus and Serrata spp.; 34%, n=37), followed by Staphylococcus spp. (29%, n=31), Pseudomonas aerugnosa (11%, n=12) and Enterococcus spp. (9%, n=10) (Table I). In terms of ndvdual organsms, S. aureus was the most common solate (n=23). Seventy per cent of Enterobacteraceae were resstant to ether cefuroxme and/or ampclln-clavulanc acd. Resstance to pperaclln-tazobactam and cefepme was observed n 29% and 34% of Enterobacteraceae cultures, respectvely. Enterobacteraceae senstvty to cprofloxacn, gentamycn and meropenem was 71%, 81% and 89% respectvely. table : Mcroorgansms cultured n the cohort of 60 patents Multple organsms were dentfed n 27 (46%) of cases. Mcroorgansm Acnetobacter baumann 7 (6%) Aeromonas hydrophyla 1 (1%) Ctrobacter amalonatcus 1 (1%) Ctrobacter koser 1 (1%) Eschercha col 5 (5%) Entecoccus faecals 1 (1%) Enterobacter cloacae 6 (6%) Enterobacter speces 1 (1%) Enterococcus avum 1 (1%) Enterococcus faecals 7 (6%) Enterococcus faecals 1 (1%) Klebsella oxytoca 2 (2%) Klebsella pneumona 5 (5%) Lactococcus lacts subsp lacts 1 (1%) Methclln-resstant Staphylococcus aureus 5 (5%) Methclln-senstve Staphylococcus aureus 19 (18%) Morganella morgan subsp sbon 2 (2%) No growth 4 (4%) Proteus marbls 7 (6%) Pseudomonas aerugnosa 12 (11%) Serrata marcescens 7 (6%) Staphylococcus capts 2 (2%) Staphylococcus epdermds 2 (2%) Staphylococcus haemolytcus 1 (1%) Staphylococcus homns4 1 (1%) Staphylococcus smulans 1 (1%) Streptococcus mts 1 (1%) Streptococcus pneumonae 1 (1%) Streptococcus pyogenes 2 (2%) Streptococcus sanguns 1 (1%) Total 108 (100%) Fourteen (77%) of Staphylococcus aureus solates were susceptble to cloxaclln. S. aureus exhbted a smlar susceptblty pattern to other common ant-staphylococcal agents, ncludng erythromycn (84%), clndamycn (84%) and trmethoprm-sulfamethoxazole (68%). Fve (23%) of the S. aureus cultures and sx (86%) of the other Staphylococcus spp. were found to be methclln-resstant. None of the methclln-resstant S. aureus strans were resstant to vancomycn. We noted a hgh rate of resstance ( 50%) of Pseudomonas aerugnosa strans to meropenem, mpenem, pperaclln-tazobactam or cefepme. More than 80% of P. aerugnosa strans were senstve to gentamycn and cprofloxacn. Ffty per cent of Enterococcus spp. were ampclln-resstant. No vancomycn-resstant Enterococcus spp. were cultured (Table II). The cause of chronc osteomyelts was haematogenous n 28% (n=17) of cases. Seventy-two per cent (n=43) of cases were classfed as contguous, wth post-operatve and post-traumatc nfecton comprsng 17% (n=10) and 55% (n=33) of all cases, respectvely. There was a sgnfcant assocaton between the orgn of the nfecton and the mcroorgansm nvolved (p-value = 0.003). The majorty of contguous nfectons nvolved mxed organsms, whle soltary nfectons by a Gram-negatve organsm were most common n the post-traumatc group (Table III). Twenty-one organsms were cultured n the 10 patents wth post-operatve nfecton. The most common pathogens were Acnetobacter baumann (n=5), Enterobacter spp. (n=5), E. col (n=4) and Enterococc (n=3). Sxty-two organsms were found n the post-traumatc group of 33 patents. The most common pathogens n ths group was methclln-senstve Staphyloccus aureus (n=7), Serrata marcescens (n=7), Pseudomonas aerugnosa (n=6), Acnetobacter baumann, Enterobacter spp., Proteus marblls, Klebsella spp. (n=4, respectvely), E. col and MRSA (n=3), respectvely. In the haematogenous group of nfectons, the majorty of nfectons were caused by a soltary Grampostve organsm. Methclln-senstve Staphylococcus aureus was cultured n nne out of the 17 haematogenous cases, although only four of these were monomcrobal n nature. Methclln-resstant Staphyloccus aureus and Pseudomonas spp. were responsble for two cases respectvely. Four (24%) of haematogenous cases were polymcrobal n nature. When applyng the Cerny and Mader classfcaton system 25% (n=15) patents were classfed as A-hosts, 55% (n=33) as B-hosts and 20% (n=12) as C-hosts. 10 Sx type-a hosts had Gram-postve nfectons, whle only three had mxed nfectons. The majorty of nfectons (70%) n B and C hosts were caused by multple organsms. Ths dfference was, however, not statstcally sgnfcant (p=0.22) (Table IV). Eleven patents (18%) were found to be HIV-postve, wth a medan CD4 count of 544 cells/mm 3 (range ). No sgnfcant dfference was noted n terms of Gram-postve, Gram-negatve, mxed pathogen or no growth cultures

4 Page 42 SA Orthopaedc Journal Wnter 2017 Vol 16 No 2 table : Ant-mcrobal senstvty and resstance patterns of the most commonly encountered bactera Serrata marcescens Pseudomona aerugnosa Proteus marbls Klebsella pneumona Enterobacter cloacae Eschercha col MSSA Acnetobacter MRSA baumann n=19 (18%) n=5 (5%) n=7 (7%) n=5 (5%) n=6 (6%) n=5 (5%) n=7 (6%) n=12 (11%) n=7 (6%) Sens Res v Sens Res v Sens Res v Sens Res v Sens Res v Sens Res v Sens Res v Sens Res v Sens Res v n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) Amoxclln 2(11) 14(77) * 5(100) * 1(14) * 5(100) * 5(83) * 4(80) * 7(100) * * * 7(100) Ampclln 2(11) 14(77) * 5(100) * 1(14) * 5(100) * 5(83) * 4(80) * 7(100) * * * 7(100) Cloxaclln 14(77) 1(5) 1(20) 4(80) 5(83) 1(16) * * * * * * * * * * * * Ampclln-clavulanc acd * * * 1(20) * * * 5(100) * 5(83) 1(20) 2(40) 6(86) * 1(8) * * 7(100) Erythromycn 16(84) 2(11) 3(60) 2(40) * * * * * * * * * * * * * * Clndamycn 16(84) 2(11) 3(60) 2(40) * * * * * * * * * * * * * * Sulbactam-cefoperazone 13(68) 5(26) 2(60) 2(60) * 7(100) 2(40) 3(60) 2(33) 3(50) 1(20) 4(80) 2(29) 5(71) * 12(100) 7(100) * Vancomycn 2(11) * 4(80) * * * * * * * * * * * * * * * Cprofloxacn * 1(5) * 3(60) * 7(100) 1(20) * 2(33) 3(50) 1(20) 3(60) 1(14) * 11(92) 1(8) 7(100) * Cefuroxme * * * 1(20) * * 1(20) 3(75) 2(33) 2(33) 1(20) 4(80) 7(100) * * 1(8) * 6(86) Cetraxone * * * * * * * 1(20) 2(33) 3(50) * 4(80) 1(14) * * * 7(100) * Gentamycn * * * * 1(17) 5(83) * 4(80) 1(16) 3(50) 6(86) * 11(92) * 7(100) * Pperaclln * * * * * 6(86) 1(20) * 2(33) 3(50) 1(20) 4(80) * * 5(42) 4(33) 7(100) * Cefepme * * * * * 6(86) 1(20) 2(40) 2(33) 2(33) 1(20) 1(20) 2(29) * 5(42) 1(8) 7(100) * Impenem * * * * * 6(86) 1(20) * 1(16) 1(16) 4(80) * 1(14) * 4(33) 3(25) 1(14) * Meropenem * * * * * 6(86) 1(20) * 1(16) 1(16) 4(80) * 1(14) * 4(33) 1(8) * * Amkacn 2(11) * * * 1(16) 5(83) * * 1(16) 1(16) 4(80) * 1(14) * 2(17) 1(8) * * Methclln-senstve Staphylococcus aureus; Methclln-resstant Staphylococcus aureus; Senstve organsms; v Resstant organsms; * No data avalable between HIV-postve and -negatve patents (p=0.18) (Table V). Furthermore, when comparng ndvdual pathogens n HIV-postve and -negatve patents, no sgnfcant dfferences were found. Whle there appeared to be an ncreased ncdence of Enterococcus spp. nfectons n HIV-postve patents, t was not statstcally sgnfcant (p=0.18). Dscusson The am of ths study was to characterse the organsms causng chronc osteomyelts n a developng world settng and to compare t to exstng data from other parts of the world. Furthermore, we examned the ant-mcrobal resstance and senstvty patterns. We also amed to determne f the pathogen profle vared n relaton to the orgn of the nfecton, the physologcal status of the host or the patent s HIV status. Whle the seres s small, a wde spectrum of organsms wth a wde varety of antbotc senstvtes was found. Ths emphasses the mportance of dentfyng the offendng bactera by tssue culture, and talorng therapy accordng to antbotc senstvty patterns. Methclln-senstve Staphylococcus aureus was the most commonly solated Gram-postve organsm (18% of all organsms), followed by other Staphylococcal speces (7%), Enterococcus (6%), methclln-resstant Staphylococcus aureus (5%) and Streptococcus spp. (4%). The most common Gramnegatve organsm was Pseudomonas aerugnosa (11% of all organsms), followed by Enterobacter, Acnetobacter, Serrata and Proteus spp. (6%, each). Our results are comparable to prevous studes from other parts of the world (Table VI). Walvogel et al., n 1970, found Staphylococcus aureus n approxmately 60% of cases. 1 In subsequent studes the relatve ncdence of staphylococcal nfectons decreased, possbly due to a rse n the ncdence of contguous nfectons. 2 Post-operatve or post-traumatc chronc osteomyelts has been assocated wth broad spectrum of organsms, ncludng those commonly assocated wth hosptal acqured nfectons lke methcllnresstant S. aureus, enterc Gram-negatve bacll and coagulase-negatve Staphylococc. 2,3 However, S. aureus appears to reman the most commonly solated organsm, regardless of aetology (Table VI). Trampuz et al. dentfed Staphylococcus aureus (30% of cases) and Gram-negatve mcro-organsms as the most common bactera nvolved n nfectons assocated wth fracture-fxaton devces. 2 Sheehy et al. found Staphylococcus aureus to be the most commonly solated pathogen among a wde range of organsms, whch ncluded Gram-negatve bacll, anaerobes and coagulase negatve staphylococc. 3

5 SA Orthopaedc Journal Wnter 2017 Vol 16 No 2 Page 43 table : Bacteral pathogens nvolved (per patent) n relaton to the aetology of the nfecton Aetology Gram-postve Gram-negatve Mxed No growth Post-operatve 2 (1.8%) 2 (1.8%) 5 (4.6%) 1 (0.9%) Post-traumatc 2 (1.8%) 12 (11.1%) 18 (16.7%) 1 (0.9%) Haematogenous 9 (8.3%) 2 (1.8%) 4 (3.7%) 2 (1.8%) Totals 13 (12.0%) 16 (14.7%) 27 (25%) 4 (3.6%) Fsher s exact test; Contguous nfectons p-value table V: Bacteral pathogens n relaton to the physologcal status of the host, n accordance wth the Cerny and Mader stagng system for chronc osteomyelts 6 Host status Gram-postve Gram-negatve Mxed No growth A-host 6 (10%) 4 (7%) 3 (7%) 1 (2%) B-host 6 (10%) 10 (17%) 16 (17%) 1 (2%) C-host 1 (2%) 2 (3%) 7 (12%) 2 (3%) Totals 13 (22%) 16 (27%) 26 (43%) 4 (7%) Fsher s exact test p-value table V: Bacteral pathogens n relaton to hv status of the patent HIV status Gram-postve Gram-negatve Mxed No growth Negatve 13 (22%) 13 (22%) 20 (33%) 3 (5%) Postve 0 (0%) 3 (5%) 7 (12%) 1 (2%) Totals 13 (22%) 16 (27%) 27 (45%) 4 (7%) Fsher s exact test p-value table V: Organsms solated n cases of adult chronc osteomyelts by prevous nvestgators Study Year Culture postvty S. aureus E. col Klebsella spp. Proteus spp. P. aerugnosa Enterobacter spp. Walvogel et al % 59.4% * * * * * Trampuz et al % 30% * * * * * Sheehy et al % 32% * * * 5% 5% Our study % 23% 5% 7% 6% 11% 7% * No data avalable In our seres, the majorty of post-operatve and posttraumatc nfectons nvolved Gram-negatve or mxed nfectons. We found a sgnfcant assocaton between the aetology of the nfecton (post-traumatc, post-operatve or haematogenous) and the causatve organsm (p-value = 0.003). Haematogenous nfectons were mostly due to Gram-postve organsms, whle the majorty of mxed nfectons occurred n contguous chronc osteomyelts. Isolated Gram-negatve nfectons were most common n the post-traumatc group of cases. In ths seres, the prevalence of polymcrobal nfectons was somewhat hgher (45%) than prevously reported n studes performed n the developed world settng. 2,3 Trampuz et al. found polymcrobal nfectons n 27% of patents. 2 Sheehy et al. reported that 29% of ther cases were polymcrobal n nature. 3 Spellberg and Lpsky revewed publcatons, from 1970 to 2011, related to the use of antbotcs n chronc osteomyelts. 11 The authors emphassed the mportance of surgcal debrdement and noted that the cure rate of chronc osteomyelts s ncreased wth surgcal resec ton of nfected and devtalsed tssue n conjuncton wth antbotc therapy. The mportant conclusons from ther revew were that oral antbotc therapy wth agents that have hgh boavalablty s comparable wth parenteral therapy; mproved cure rates are acheved wth the addton of rfampcn; and that the duraton of antbotc therapy should be ndvdualsed based on clncal, haematologcal, and radologcal response. 11 The authors also recommended that antbotc therapy should be talored to local senstvty patterns. The organsms cultured n ths seres exhbted a wde range of antbotc senstvtes. Many commonly employed generc antbotc regmens may be neffectve n our settng. It s alarmng that 70% of the Enterobacteraceae spp. n ths seres were resstant to ether cefuroxme or ampclln-clavulanc acd and 34% of these organsms were resstant to cefepme.

6 Page 44 SA Orthopaedc Journal Wnter 2017 Vol 16 No 2 Our fndngs conflct wth prevous data showng that cephalosporns generally have a good actvty aganst commonly solated enterobacteraceae. 12 In our seres, Enterobacteraceae spp. exhbted reasonable senstvty to cprofloxacn (71%), gentamycn (81%) and meropenem (89%). Ths s consstent wth the fndngs of Spellberg et al. who found a hgh cure rate wth a combnaton use of cprofloxacn and trmethoprmsulfamethoxazole when gven for for 8 16 weeks. 11 In our seres, 77% of Staphylococcus aureus were susceptble to cloxaclln. Jones et al. reported smlar results, wth more than 99% S. aureus susceptble to oxaclln. 12 Methclln-resstant S. aureus was however common n our seres, wth 80% of strans beng susceptble to vancomycn. Vancomycn penetrates bone relatvely poorly, wth the rato of bone to serum concentraton beng only approxmately 20% n nfected bone. 13 Cefazoln outperformed vancomycn n one seres, despte ts bone penetraton beng nferor to that of vancomycn (approxmately 15%). 14 Meropenem does not appear to fare much better, wth a bone penetraton of approxmately 17%. 15 Intravenous qunolone antbotcs are another opton for Gram-negatve cover and exhbt excellent bone penetraton. The bone/serum rato of ntravenous cprofloxacn has been reported to be up to 47% n cortcal bone. 16 Convenently, the bone penetraton of oral cprofloxacn s also reasonable, reachng 35% at a dose of 500 mg. 17 Takng these results nto account the generc antbotc regmen (for use followng surgery) proposed by McNally, nvolvng the use parenteral vancomycn and meropenem, appears to be reasonable. 18 Cprofloxacn (or another qunolone) appears to be a useful alternatve to meropenem for aerobc Gram-negatve bacll, and prevous clncal studes support ts use. 19 Cefepme appears to reman an excellent opton n Gram-negatve nfectons due to relatvely low resstance and excellent bone penetraton. 20 In our seres, the bacteral pathogen profle dd not vary n relaton to the patent s HIV status. Prevous lterature dentfed Staphylococcus aureus as the most common organsm causng osteoartcular nfectons n HIV patents. 10,21 Zalavras et al. looked at the mcrobology of chronc osteomyelts n patents lvng wth the human mmunodefcency vrus and found S. aureus n 50% of cases, polymcrobal nfectons n 35% and no growth n three cases. 21 They also found no osseous opportunstc nfecton n HIV patents wth mmunodefcency. Busch et al. also reported Staphylococcus aureus (n 8 of 19 patents) as the most common agent n HIVnfected patents wth chronc osteomyelts. 10 Staphylococcus aureus was also shown to be the most common organsm responsble for osteoartcular nfectons n ntravenous drug abusers wth mmunodefcency vrus. 22 Informaton about the causatve agents was avalable n 88 (27%) of the 330 osteomyelts cases dentfed by the Adult/Adolescent Spectrum of HIV Dsease project of the Centers for Dsease Control (CDC). Staphylococcus aureus was the most common pathogen, comprsng 48% of dentfed organsms. In our study, the majorty of HIV-postve patents presented wth polymcrobal nfectons and there was no assocaton between HIV status and causatve bactera (p-value = 0.18). Therefore, n our seres, HIV nfecton does not appear to alter the mcrobology of chronc osteomyelts. There s nsuffcent evdence to suggest that clncans should change ther antbotc protocol based on the HIV status of ther patents, and accordng to the avalable data t does not appear necessary to add routne antbotc coverage for opportunstc nfectons n HIV patents. Prevous studes dd not stratfy nfectve organsms n relaton to the Cerny and Mader host status or anatomcal nature of the dsease. In our study shows that there s no sgnfcant assocaton between host status (A, B and C-host) and the causatve organsm (p-value = 0.221). Although t dd not reach statstcal sgnfcance, type C-hosts were found to have predomnantly polymcrobal nfectons. The small number of cases n ths seres s a shortcomng and much larger studes are requred before resolute recommendatons can be made n terms of generc antbotc selecton. The absence of routne anaerobe cultures s a further shortcomng. In larger seres, anaerobc nfectons have accounted for a small, but sgnfcant, number of nfectons. An addtonal shortcomng s the absence of data relatng to pror antbotc therapy and number of prevous surgcal attempts. Pror treatment may nfluence the bacteral profle and thus the cultured organsm may not necessarly be the orgnal causatve organsm. Comparatve studes are requred to determne the clncal effcacy of dfferent antbotc regmens. Concluson The causatve mcroorgansm n chronc osteomyelts was found to be assocated wth aetology of the nfecton. Whle the majorty of haematogenous chronc osteomyelts stll nvolved a soltary Gram-postve organsm, the ncdence of Gram-negatve nfectons was found to be hgher than prevously reported. Contguous chronc osteomyelts was mostly polymcrobal n nature and soltary nfectons nvolvng a Gram-negatve organsm was most common n the post-traumatc group. The bacteral pathogen dd not vary n relaton to the HIV status of the patent or the physologcal status of the host. Complance wth ethcs gudelnes Conflct of nterest: The authors declare that they have no conflct of nterests and that no fnancal support was receved for ths study.

7 SA Orthopaedc Journal Wnter 2017 Vol 16 No 2 Page 45 Ethcs approval: Ethcal approval was obtaned from our nsttuton s ethcs revew board pror to commencement of the study (BREC: BE020/14). The study was conducted accordng to the ethcal prncples for medcal research on human subjects as defned by the World Medcal Assocaton Declaraton of Helsnk (amended at the MA General Assembly, Seoul, Oct 2008). Authors contrbutons: All authors made contrbutons toward the concepton and desgn of the research, acquston of data and draftng of the manuscrpt. The fnal manuscrpt was read and approved by all the authors. References 1. Lew DP, Waldvogel FA. Current concepts osteomyelts. N Eng J Med 1997;336: Trampuz A, Zmmerl W. Dagnoss and treatment of nfectons assocated wth fracture- fxaton devces. Injury 2006;37(Suppl 2): Sheehy SH, Atkns BA, Bejon P, Byren I, Wylle D, Athanasou NA, Berendt AR, McNally MA. The mcrobology of chronc osteomyelts: Prevalence of resstance to common emprcal ant-mcrobal regmens. J Infecton 2010;60: Gustlo RB, Merkow RL, Templeton D. The management of open fractures. J Bone Jont Surg Am 1990;72(2); Walter G, Kemmerer M, Kappler C, Hoffmann R. Treatment Algorthms for Chronc Osteomyelts. Dtsch Arztebl Int 2012;109(14): Maras LC, Ferrera N, Sartorus B, Aldous C, Le Roux TLB. A modfed stagng system for chronc osteomyelts. J Orthop 2015;12: Cerny G, Mader JT, Pennnck JJ. A clncal stagng system for adult Osteomyelts. Cln Orthop Relat Res 2003;414: Cerny G. Surgcal treatment of osteomyelts. Plast Reconstr Surg 2011;127(Suppl1): Lew DP, Waldvogel FA. Osteomyelts. Lancet 2004;364: Busch V, Regez R, Heere B, Wllems J. Osteoartcular nfectons n HIV-nfected patents: 23 cases among 1,515 HIVnfected patents. Acta Orthop 2009;78(6): Spellberg B, Lpsky A. Systemc antbotc therapy for chronc osteomyelts n adults clncal nfectous dseases. Cln Infect Ds 2012;54(3): Jones ME, Karlowsky JA, Dragh DC. Antbotc susceptblty of bactera most commonly solated from bone related nfectons: the role of cephalosporns n antmcrobal therapy. Int J Antmcrob Agents 2004;23: Grazan AL, Lawson LA, Gbson GA, Stenberg MA, MacGregor RR. Vancomycn concentratons n nfected and non-nfected human bone. Antmcrob Agents chemother 1988;32: Wllams DN, Gustlo RB, Beverly R, Knd AC. Bone and serum concentratons of fve cephalosporn drugs. Relevance to prophylaxs and treatment n orthopedc surgery. Cln Orthop 1983;179: Sano T, Sakura M, Doh S, et al. Investgaton of meropenem levels n the human bone marrow blood, bone, jont flud and jont tssues. Jpn J Antbot 1993;46: Messner A, Borner K. Concentraton of cprofloxacn n bone tssue. Aktuelle Traumatol 1993;23: Fong IW, Ledbetter WH, Vandenbroucke AC, Smbul M, Rahm V. Cprofloxacn concentratons n bone and muscle after oral dosng. Antmcrob Agents Chemother 1986;29: McNally M, Nagarajah K. Osteomyelts. Orthop Trauma 2010;24(6): Glbert DN, Tce AD, Marsh PK, Craven PC, Prehem LC. Am J Med 1987;82(4A): Brelh D, Bosell E, Bel JC, Chassard D, Saux MC, Allaouchche B. Dffuson of cefepme nto cancellous and cortcal bone tssue. J Chemother 2003;15: Zalavras C, Gupta N, Patzaks M, Holtom P. Mcrobology of osteomyelts n patents nfected wth the human mmunodefcency vrus. Cln Orthop Relat Res 2005;439; Belzunegu J, Gonzalez C, Lopez L, Osteoartcular and muscle nfectons lesons n patents wth the human mmunodefcency vrus. Cln Rheum 1997;16(5): Ths artcle s also avalable onlne on the SAOA webste ( and the ScELO webste ( Follow the drectons on the Contents page of ths journal to access t. SAOJ