Pneumococcal infection is common in children with HIV infection, but osteomyelits is unusual. The best treatment for bone and joint infection due to antibiotic resistant pneumococci is not known, especially in immunocompromised children

AL Pozniak

American Academy Of Pediatrics

Andrew I Riordan

Clive Graham

JJ Ross

JS Bradley

KP Klugman

ME Shirtliff

N Arlievsky

Shazia Adalat

SL Kaplan

SR Brian

T O'Reilly

English

PubMed

Crossref

Successful treatment with azithromycin and rifampicin of penicillin and cephalosporin insensitive pneumococcal osteomyelitis in a child with HIV infection: a case report

Springer - Publisher Connector

BioMed CentralCases Journal
ssOpen AcceCase Report
Successful treatment with azithromycin and rifampicin of penicillin 
and cephalosporin insensitive pneumococcal osteomyelitis in a child 
with HIV infection: a case report
Andrew I Riordan*1,3, Shazia Adalat1 and Clive Graham2
Address: 1Department of Child Health, Birmingham Heartlands Hospital, UK, 2Department of Microbiology, Birmingham Children's Hospital, 
Birmingham, UK and 3Haematology Treatment Centre, Royal Liverpool Children's Hospital, Eaton Road, Liverpool, L12 2AP, UK
Email: Andrew I Riordan* - andrew.riordan@alderhey.nhs.uk; Shazia Adalat - s.adalat@nhs.net; Clive Graham - Clive.Graham@BCH.nhs.uk
* Corresponding author    
Abstract
Pneumococcal infection is common in children with HIV infection, but osteomyelits is unusual. The
best treatment for bone and joint infection due to antibiotic resistant pneumococci is not known,
especially in immunocompromised children.
A 6 month old girl, infected with HIV by mother to child transmission, had recently started
combination antiretroviral therapy (cART). She presented with osteomyelitis of the left radius
confirmed on bone scan. Blood cultures grew Streptococcus pneumoniae 9S resistant to penicillin,
with reduced susceptibility to ceftriaxone.
Osteomyelitis was treated with parenteral teicoplanin, oral rifampicin and azithromycin. After two
weeks of treatment she developed rash and fever. These were thought to be a drug eruption and
resolved when teicoplanin was stopped. She completed a 3 month course of rifampicin and
azithromycin and continued on cART. She has normal function of her left wrist 18 months after
treatment. She remains on her original cART regimen with an undetectable viral load and normal
CD4 count (34%; 1398 × 106/l).
The combination of rifampicin and azithromycin was well tolerated, simple to administer and
effective. This combination deserves further study in bone and joint infection caused by antibiotic
resistant Gram positive bacteria.
Introduction
Streptococcus pneumoniae is the commonest pathogen caus-
ing bacteraemia in children infected with the human
immunodeficiency virus (HIV). However osteomyelitis is
reported infrequently, and osteomyelitis due to penicillin-
resistant S. pneumoniae has not been reported previously
in this patient group [1].
We report successful treatment of penicillin and cepha-
losporin non-susceptible pneumococcal osteomyelitis in
a child with HIV, using rifampicin and azithromycin.
Case presentation
A 6 month old HIV positive black African girl presented
with a two week history of intermittent fever. Her mother
had been found to be HIV positive when 30 weeks preg-
nant. Mother was given combivir and nevirapine and her
Published: 29 October 2008
Cases Journal 2008, 1:283 doi:10.1186/1757-1626-1-283
Received: 8 September 2008
Accepted: 29 October 2008
This article is available from: http://www.casesjournal.com/content/1/1/283
© 2008 Riordan et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 3
(page number not for citation purposes)
Cases Journal 2008, 1:283 http://www.casesjournal.com/content/1/1/283viral load fell from 20,000 copies/ml to 290 copies/ml at
delivery. The infant was given zidovudine for 4 weeks after
delivery. However pro-viral DNA for HIV was positive at
birth in the infant, implying antenatal infection with HIV.
The infant remained well, thrived and had a CD4 count
above 35%. She was therefore not started immediately on
antiretroviral therapy, but was given prophylactic co-tri-
moxazole.
On presenting with fever aged six months there were no
physical signs of note. Blood cultures were taken which
grew Streptococcus pneumoniae with reduced sensitivity to
penicillin, resistant to trimethoprim but sensitive to
cephalosporins and macrolides. She was given intrave-
nous cefotaxime for 3 days then oral erythromycin for 2
weeks.
On review one month later she had been intermittently
febrile since stopping antibiotics. Repeat blood cultures
showed no growth, but she was given 14 days of
parenteral ceftriaxone empirically. Following this she was
commenced on combination antiretroviral therapy
(cART; zidovudine, lamivudine, abacavir and nevirapine),
because of these symptoms and falling CD4 count
(17%{221 × 106/l}).
She re- presented aged 8 months (one month after starting
cART) with a swollen left wrist, fever and raised C-reactive
protein (86 mg/l). A radio-isotope bone scan was compat-
ible with osteomyelitis of the left radius. Blood cultures
grew Streptococcus pneumoniae 9S resistant to penicillin
(MIC >2 mg/l) and trimethoprim, with reduced sensitivity
to cephalosporins (MIC 1–2 mg/l), but sensitive to vanco-
mycin, rifampicin and macrolides.
Aspiration of bone was not done since blood cultures
were positive. She was given parenteral teicoplanin (10
mg/kg once daily) with oral rifampicin (10 mg/kg twice
daily) and azithromycin (10 mg/kg once daily). After 2
weeks of treatment she developed rash and fever. These
were thought to be a drug eruption and resolved when
teicoplanin was stopped. She completed a 3 month course
of rifampicin and azithromycin and continued on cART.
Subsequent blood cultures were negative.
Eighteen months after treatment her left wrist is normal,
she remains on her original cART regimen with an unde-
tectable viral load and CD4 count of 34% (1398 × 106/l).
Discussion
S pneumoniae causes 3–6% of bone and joint infections in
children with normal immunity [2,3]. Penicillin and/or
ampicillin are the drugs most commonly used to treat
bone and joint infections due to susceptible strains, whilst
vancomycin and clindamycin or ceftriaxone are used for
penicllin-nonsusceptible strains [3]. The best treatment
for antibiotic resistant pneumococcal bone and joint
infection is not known. Clinical response to treatment was
similar in children with bone and joint infection due to
penicillin non-susceptible pneumococci when compared
with children infected by penicillin susceptible strains [2].
The combination of rifampicin and azithromycin was
effective in treating osteomyelitis caused by a penicillin
and cephalosporin non-susceptible pneumococcus in a
child with HIV. Rifampicin and azithromycin have differ-
ent sites of action in bacteria. This combination has been
shown to be effective in animal models of staphylococcal
osteomyelitis [4]. There is also one case report of an adult
with antibiotic resistant pneumococcal infection in a
prosthetic joint where these antibiotics were successfully
used sequentially, but not in combination [5].
Both azithromycin and rifampicin achieve high levels in
bone. However azithromycin monotherapy is ineffective
for the treatment of experimental staphylococcal osteo-
myelitis, [6] whilst rifampicin monotherapy is associated
with the emergence of rifampicin resistance.
In the UK macrolide resistance is more common in peni-
cillin non-susceptible S pneumoniae, making macrolides in
general less useful for treating osteomyelitis. However in
this case the isolate was macrolide sensitive, despite peni-
cillin and cephalosporin resistance.
Rifampicin can also interact with anti-retroviral drugs,
especially protease inhibitors and nevirapine. Current
advice is that low dose ritonavir/protease inhibitors com-
binations or nevirapine should not be given with
rifampicin [7]. In our case we chose to continue nevirap-
ine since we were unable to use efavirenz, due to the
child's young age (less than 3 years), and felt there was no
advantage in changing to a protease inhibitor. The child's
viral load became undetectable on cART, despite the use
of rifampicin.
Other antibiotics may have been effective in this case, but
also had potential drawbacks. Ceftriaxone may be effec-
tive for non-ceftriaxone susceptible pneumococcal infec-
tion outside the central nervous system, as long as the
MIC is < 2.0 mg/l [8]. However this reported series did not
include any children with osteomyelitis. We felt we could
not rely on this agent in an immunocompromised child
with osteomyelitis, particularly since she had recently
received a two week course of ceftriaxone and failed to
respond clinically. Vancomycin is suggested for cepha-
losporin insensitive pneumococcal meningitis [9], but
may have decreased effectiveness in bone and is unsuita-
ble for outpatient therapy. We were unable to continue
teicoplanin because of a drug eruption. The two weeks ofPage 2 of 3
(page number not for citation purposes)
Cases Journal 2008, 1:283 http://www.casesjournal.com/content/1/1/283Publish with BioMed Central   and  every 
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Your research papers will be:
available free of charge to the entire biomedical community
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BioMedcentral
teicoplanin our patient received was unlikely to have been
sufficient treatment. Clindamycin is active in animal
models of staphylococcal osteomyelitis [6]. However the
suspension has a very poor taste, making it inappropriate
in young children for the prolonged oral administration
needed to treat osteomyelitis. Linezolid is active against
pneumococci, and may have been effective [9]. However
long term use can produce bone marrow depression. This
would have been our choice if the child had failed to
respond to azithromycin and rifampicin.
Preventive strategies against pneumococcal disease may
have been useful in this child. Prophylactic co-trimoxa-
zole gives some protection against bacterial infection in
HIV positive children, but the organism in this case was
trimethoprim resistant. Conjugate pneumococcal vaccine
provides some protection, even in HIV positive children
[10]. A 7 valent conjugate pneumococcal vaccine is now
recommended for all HIV positive children in the UK.
This may have given some protection against the pneumo-
coccal serotype in this case by cross protection from the 9F
component of the vaccine.
Conclusion
The combination of rifampicin and azithromycin was
well tolerated, simple to administer and effective in treat-
ing penicillin and cephalosporin insensitive pneumococ-
cal osteomyelitis. This combination deserves further study
for treatment of bone and joint infections, especially
those due to antibiotic resistant Gram positive bacteria.
Consent
Written informed consent was obtained from the patient's
mother for publication of this case report and any accom-
panying images. A copy of the written consent is available
for review by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests
Authors' contributions
AR helped to draft and revised the manuscript. SA drafted
the manuscript, CG revised the manuscript. All authors
read and approved the final manuscript.
Acknowledgements
We thank Dr Mike Sharland for his helpful advice about this girl.
References
1. Arlievsky N, Li KI, Munoz JL: Septic arthritis with osteomyelitis
due to Streptococcus pneumoniae in Human Immunodefi-
ciency Virus-Infected children.  Clin Infect Dis 1998, 27:898-899.
2. Bradley JS, Kaplan SL, Tan TQ, Barson WJ, Arditi M, Schutze GE,
Wald ER, Givner LB, Mason EO: Pediatric pneumococcal bone
and joint infections. The Pediatric Multicenter Pneumococ-
cal Surveillance Study Group.  Pediatrics 1998, 102:1376-82.
3. Ross JJ, Saltzman CL, Carling P, Shapiro DS: Pneumococcal Septic
Arthritis: Review of 190 Cases.  Clin Infect Dis 2003, 36:319-27.
4. Shirtliff ME, Mader JT, Calhoun J: Oral rifampin plus azithromycin
or clarithromycin to treat osteomyelitis in rabbits.  Clin Orthop
1999, 359:229-36.
5. Brian SR, Kimbrough RC 3rd: Salvage of a prosthetic knee joint
infected with resistant pneumococcus. A case report.  J Bone
Joint Surg Am 2004, 86-A:2302-4.
6. O'Reilly T, Kunz S, Sande E, Zak O, Sande MA, Tauber MG: Relation-
ship between antibiotic concentration in bone and efficacy of
treatment of staphylococcal osteomyelitis in rats: azithro-
mycin compared with clindamycin and rifampin.  Antimicrob
Agents Chemother 1992, 36:2693-7.
7. Pozniak AL, Miller RF, Lipman MCI, Freedman AR, Ormerod LP, John-
son MA, Collins S, Lucas SB, on behalf of the BHIVA guidelines writing
committee: BHIVA guidelines for TB/HIV infection 2005 [http://
www.bhiva.org].
8. Kaplan SL, Mason EO Jr, Barson WJ, Tan TQ, Schutze GE, Bradley JS,
Givner LB, Kim KS, Yogev R, Wald ER: Outcome of invasive infec-
tions outside the central nervous system caused by Strepto-
coccus pneumoniae isolates nonsusceptible to ceftriazone in
children treated with beta-lactam antibiotics.  Pediatr Infect Dis
J 2001, 20:392-6.
9. American Academy Of Pediatrics: Committee on Infectious Dis-
eases. Therapy for Children with Invasive Pneumococcal
Infections.  Pediatr 1997, 99:289-299.
10. Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, Pierce
N, Vaccine Trialists Group: A trial of a 9-valent pneumococcal
conjugate vaccine in children with and those without HIV
infection.  N Engl J Med 2003, 349:1341-8.Page 3 of 3
(page number not for citation purposes)


Pneumococcal infection is common in children with HIV infection, but osteomyelits is unusual. The best treatment for bone and joint infection due to antibiotic resistant pneumococci is not known, especially in immunocompromised children.A 6 month old girl, infected with HIV by mother to child transmission, had recently started combination antiretroviral therapy (cART). She presented with osteomyelitis of the left radius confirmed on bone scan. Blood cultures grew Streptococcus pneumoniae 9S resistant to penicillin, with reduced susceptibility to ceftriaxone.Osteomyelitis was treated with parenteral teicoplanin, oral rifampicin and azithromycin. After two weeks of treatment she developed rash and fever. These were thought to be a drug eruption and resolved when teicoplanin was stopped. She completed a 3 month course of rifampicin and azithromycin and continued on cART. She has normal function of her left wrist 18 months after treatment. She remains on her original cART regimen with an undetectable viral load and normal CD4 count (34%; 1398 x 106/l).The combination of rifampicin and azithromycin was well tolerated, simple to administer and effective. This combination deserves further study in bone and joint infection caused by antibiotic resistant Gram positive bacteria

Riordan, Andrew I

Adalat, Shazia

Graham, Clive

Heart of England: HEFT Repository

BioMed CentralCases JournalssOpen AcceCase ReportSuccessful treatment with azithromycin and rifampicin of penicillin and cephalosporin insensitive pneumococcal osteomyelitis in a child with HIV infection: a case reportAndrew I Riordan*1,3, Shazia Adalat1 and Clive Graham2Address: 1Department of Child Health, Birmingham Heartlands Hospital, UK, 2Department of Microbiology, Birmingham Children's Hospital, Birmingham, UK and 3Haematology Treatment Centre, Royal Liverpool Children's Hospital, Eaton Road, Liverpool, L12 2AP, UKEmail: Andrew I Riordan* - andrew.riordan@alderhey.nhs.uk; Shazia Adalat - s.adalat@nhs.net; Clive Graham - Clive.Graham@BCH.nhs.uk* Corresponding author    AbstractPneumococcal infection is common in children with HIV infection, but osteomyelits is unusual. Thebest treatment for bone and joint infection due to antibiotic resistant pneumococci is not known,especially in immunocompromised children.A 6 month old girl, infected with HIV by mother to child transmission, had recently startedcombination antiretroviral therapy (cART). She presented with osteomyelitis of the left radiusconfirmed on bone scan. Blood cultures grew Streptococcus pneumoniae 9S resistant to penicillin,with reduced susceptibility to ceftriaxone.Osteomyelitis was treated with parenteral teicoplanin, oral rifampicin and azithromycin. After twoweeks of treatment she developed rash and fever. These were thought to be a drug eruption andresolved when teicoplanin was stopped. She completed a 3 month course of rifampicin andazithromycin and continued on cART. She has normal function of her left wrist 18 months aftertreatment. She remains on her original cART regimen with an undetectable viral load and normalCD4 count (34%; 1398 × 106/l).The combination of rifampicin and azithromycin was well tolerated, simple to administer andeffective. This combination deserves further study in bone and joint infection caused by antibioticresistant Gram positive bacteria.IntroductionStreptococcus pneumoniae is the commonest pathogen caus-ing bacteraemia in children infected with the humanimmunodeficiency virus (HIV). However osteomyelitis isreported infrequently, and osteomyelitis due to penicillin-resistant S. pneumoniae has not been reported previouslyin this patient group [1].We report successful treatment of penicillin and cepha-losporin non-susceptible pneumococcal osteomyelitis ina child with HIV, using rifampicin and azithromycin.Case presentationA 6 month old HIV positive black African girl presentedwith a two week history of intermittent fever. Her motherhad been found to be HIV positive when 30 weeks preg-nant. Mother was given combivir and nevirapine and herPublished: 29 October 2008Cases Journal 2008, 1:283 doi:10.1186/1757-1626-1-283Received: 8 September 2008Accepted: 29 October 2008This article is available from: http://www.casesjournal.com/content/1/1/283© 2008 Riordan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 3(page number not for citation purposes)Cases Journal 2008, 1:283 http://www.casesjournal.com/content/1/1/283viral load fell from 20,000 copies/ml to 290 copies/ml atdelivery. The infant was given zidovudine for 4 weeks afterdelivery. However pro-viral DNA for HIV was positive atbirth in the infant, implying antenatal infection with HIV.The infant remained well, thrived and had a CD4 countabove 35%. She was therefore not started immediately onantiretroviral therapy, but was given prophylactic co-tri-moxazole.On presenting with fever aged six months there were nophysical signs of note. Blood cultures were taken whichgrew Streptococcus pneumoniae with reduced sensitivity topenicillin, resistant to trimethoprim but sensitive tocephalosporins and macrolides. She was given intrave-nous cefotaxime for 3 days then oral erythromycin for 2weeks.On review one month later she had been intermittentlyfebrile since stopping antibiotics. Repeat blood culturesshowed no growth, but she was given 14 days ofparenteral ceftriaxone empirically. Following this she wascommenced on combination antiretroviral therapy(cART; zidovudine, lamivudine, abacavir and nevirapine),because of these symptoms and falling CD4 count(17%{221 × 106/l}).She re- presented aged 8 months (one month after startingcART) with a swollen left wrist, fever and raised C-reactiveprotein (86 mg/l). A radio-isotope bone scan was compat-ible with osteomyelitis of the left radius. Blood culturesgrew Streptococcus pneumoniae 9S resistant to penicillin(MIC >2 mg/l) and trimethoprim, with reduced sensitivityto cephalosporins (MIC 1–2 mg/l), but sensitive to vanco-mycin, rifampicin and macrolides.Aspiration of bone was not done since blood cultureswere positive. She was given parenteral teicoplanin (10mg/kg once daily) with oral rifampicin (10 mg/kg twicedaily) and azithromycin (10 mg/kg once daily). After 2weeks of treatment she developed rash and fever. Thesewere thought to be a drug eruption and resolved whenteicoplanin was stopped. She completed a 3 month courseof rifampicin and azithromycin and continued on cART.Subsequent blood cultures were negative.Eighteen months after treatment her left wrist is normal,she remains on her original cART regimen with an unde-tectable viral load and CD4 count of 34% (1398 × 106/l).DiscussionS pneumoniae causes 3–6% of bone and joint infections inchildren with normal immunity [2,3]. Penicillin and/orampicillin are the drugs most commonly used to treatbone and joint infections due to susceptible strains, whilstvancomycin and clindamycin or ceftriaxone are used forpenicllin-nonsusceptible strains [3]. The best treatmentfor antibiotic resistant pneumococcal bone and jointinfection is not known. Clinical response to treatment wassimilar in children with bone and joint infection due topenicillin non-susceptible pneumococci when comparedwith children infected by penicillin susceptible strains [2].The combination of rifampicin and azithromycin waseffective in treating osteomyelitis caused by a penicillinand cephalosporin non-susceptible pneumococcus in achild with HIV. Rifampicin and azithromycin have differ-ent sites of action in bacteria. This combination has beenshown to be effective in animal models of staphylococcalosteomyelitis [4]. There is also one case report of an adultwith antibiotic resistant pneumococcal infection in aprosthetic joint where these antibiotics were successfullyused sequentially, but not in combination [5].Both azithromycin and rifampicin achieve high levels inbone. However azithromycin monotherapy is ineffectivefor the treatment of experimental staphylococcal osteo-myelitis, [6] whilst rifampicin monotherapy is associatedwith the emergence of rifampicin resistance.In the UK macrolide resistance is more common in peni-cillin non-susceptible S pneumoniae, making macrolides ingeneral less useful for treating osteomyelitis. However inthis case the isolate was macrolide sensitive, despite peni-cillin and cephalosporin resistance.Rifampicin can also interact with anti-retroviral drugs,especially protease inhibitors and nevirapine. Currentadvice is that low dose ritonavir/protease inhibitors com-binations or nevirapine should not be given withrifampicin [7]. In our case we chose to continue nevirap-ine since we were unable to use efavirenz, due to thechild's young age (less than 3 years), and felt there was noadvantage in changing to a protease inhibitor. The child'sviral load became undetectable on cART, despite the useof rifampicin.Other antibiotics may have been effective in this case, butalso had potential drawbacks. Ceftriaxone may be effec-tive for non-ceftriaxone susceptible pneumococcal infec-tion outside the central nervous system, as long as theMIC is < 2.0 mg/l [8]. However this reported series did notinclude any children with osteomyelitis. We felt we couldnot rely on this agent in an immunocompromised childwith osteomyelitis, particularly since she had recentlyreceived a two week course of ceftriaxone and failed torespond clinically. Vancomycin is suggested for cepha-losporin insensitive pneumococcal meningitis [9], butmay have decreased effectiveness in bone and is unsuita-ble for outpatient therapy. We were unable to continueteicoplanin because of a drug eruption. The two weeks ofPage 2 of 3(page number not for citation purposes)Cases Journal 2008, 1:283 http://www.casesjournal.com/content/1/1/283Publish with BioMed Central   and  every scientist can read your work free of charge"BioMed Central will be the most significant development for disseminating the results of biomedical research in our lifetime."Sir Paul Nurse, Cancer Research UKYour research papers will be:available free of charge to the entire biomedical communitypeer reviewed and published immediately upon acceptancecited in PubMed and archived on PubMed Central yours — you keep the copyrightSubmit your manuscript here:http://www.biomedcentral.com/info/publishing_adv.aspBioMedcentralteicoplanin our patient received was unlikely to have beensufficient treatment. Clindamycin is active in animalmodels of staphylococcal osteomyelitis [6]. However thesuspension has a very poor taste, making it inappropriatein young children for the prolonged oral administrationneeded to treat osteomyelitis. Linezolid is active againstpneumococci, and may have been effective [9]. Howeverlong term use can produce bone marrow depression. Thiswould have been our choice if the child had failed torespond to azithromycin and rifampicin.Preventive strategies against pneumococcal disease mayhave been useful in this child. Prophylactic co-trimoxa-zole gives some protection against bacterial infection inHIV positive children, but the organism in this case wastrimethoprim resistant. Conjugate pneumococcal vaccineprovides some protection, even in HIV positive children[10]. A 7 valent conjugate pneumococcal vaccine is nowrecommended for all HIV positive children in the UK.This may have given some protection against the pneumo-coccal serotype in this case by cross protection from the 9Fcomponent of the vaccine.ConclusionThe combination of rifampicin and azithromycin waswell tolerated, simple to administer and effective in treat-ing penicillin and cephalosporin insensitive pneumococ-cal osteomyelitis. This combination deserves further studyfor treatment of bone and joint infections, especiallythose due to antibiotic resistant Gram positive bacteria.ConsentWritten informed consent was obtained from the patient'smother for publication of this case report and any accom-panying images. A copy of the written consent is availablefor review by the Editor-in-Chief of this journal.Competing interestsThe authors declare that they have no competing interestsAuthors' contributionsAR helped to draft and revised the manuscript. SA draftedthe manuscript, CG revised the manuscript. All authorsread and approved the final manuscript.AcknowledgementsWe thank Dr Mike Sharland for his helpful advice about this girl.References1. Arlievsky N, Li KI, Munoz JL: Septic arthritis with osteomyelitisdue to Streptococcus pneumoniae in Human Immunodefi-ciency Virus-Infected children.  Clin Infect Dis 1998, 27:898-899.2. Bradley JS, Kaplan SL, Tan TQ, Barson WJ, Arditi M, Schutze GE,Wald ER, Givner LB, Mason EO: Pediatric pneumococcal boneand joint infections. The Pediatric Multicenter Pneumococ-cal Surveillance Study Group.  Pediatrics 1998, 102:1376-82.3. Ross JJ, Saltzman CL, Carling P, Shapiro DS: Pneumococcal SepticArthritis: Review of 190 Cases.  Clin Infect Dis 2003, 36:319-27.4. Shirtliff ME, Mader JT, Calhoun J: Oral rifampin plus azithromycinor clarithromycin to treat osteomyelitis in rabbits.  Clin Orthop1999, 359:229-36.5. Brian SR, Kimbrough RC 3rd: Salvage of a prosthetic knee jointinfected with resistant pneumococcus. A case report.  J BoneJoint Surg Am 2004, 86-A:2302-4.6. O'Reilly T, Kunz S, Sande E, Zak O, Sande MA, Tauber MG: Relation-ship between antibiotic concentration in bone and efficacy oftreatment of staphylococcal osteomyelitis in rats: azithro-mycin compared with clindamycin and rifampin.  AntimicrobAgents Chemother 1992, 36:2693-7.7. Pozniak AL, Miller RF, Lipman MCI, Freedman AR, Ormerod LP, John-son MA, Collins S, Lucas SB, on behalf of the BHIVA guidelines writingcommittee: BHIVA guidelines for TB/HIV infection 2005 [http://www.bhiva.org].8. Kaplan SL, Mason EO Jr, Barson WJ, Tan TQ, Schutze GE, Bradley JS,Givner LB, Kim KS, Yogev R, Wald ER: Outcome of invasive infec-tions outside the central nervous system caused by Strepto-coccus pneumoniae isolates nonsusceptible to ceftriazone inchildren treated with beta-lactam antibiotics.  Pediatr Infect DisJ 2001, 20:392-6.9. American Academy Of Pediatrics: Committee on Infectious Dis-eases. Therapy for Children with Invasive PneumococcalInfections.  Pediatr 1997, 99:289-299.10. Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N, PierceN, Vaccine Trialists Group: A trial of a 9-valent pneumococcalconjugate vaccine in children with and those without HIVinfection.  N Engl J Med 2003, 349:1341-8.Page 3 of 3(page number not for citation purposes)

Successful treatment with azithromycin and rifampicin of penicillin and cephalosporin insensitive pneumococcal osteomyelitis in a child with HIV infection: a case report.

HEFT Repository

American Academy Of Pediatrics: Committee on Infectious Diseases. Therapy for Children with Invasive Pneumococcal Infections. Pediatr

DS: Pneumococcal Septic Arthritis: Review of 190 Cases. Clin Infect Dis

EO: Pediatric pneumococcal bone and joint infections. The Pediatric Multicenter Pneumococcal Surveillance Study Group. Pediatrics

ER: Outcome of invasive infections outside the central nervous system caused by Streptococcus pneumoniae isolates nonsusceptible to ceftriazone in children treated with beta-lactam antibiotics. Pediatr Infect Dis J

JL: Septic arthritis with osteomyelitis due to Streptococcus pneumoniae in Human Immunodeficiency Virus-Infected children. Clin Infect Dis

Kimbrough RC 3rd: Salvage of a prosthetic knee joint infected with resistant pneumococcus. A case report.

Oral rifampin plus azithromycin or clarithromycin to treat osteomyelitis in rabbits. Clin Orthop

Tauber MG: Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin. Antimicrob Agents Chemother

Vaccine Trialists Group: A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection.

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Successful treatment with azithromycin and rifampicin of penicillin and cephalosporin insensitive pneumococcal osteomyelitis in a child with HIV infection: a case report

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