Infectious Diseases Society of America Emerging Infections Network Comments for Query: Osteomyelitis in Children Choice of antimicrobial At our institution, we typically start with clindamycin (unless child is toxic). If no improvement on clindamycin we then proceed with biopsy. [KY] Never use rifampin alone. [CA, FL, NC, NY, WA] Rifampin is being used as a helper drug for synergy in complicated cases. [OH] Will add rifampin to other antibiotics frequently (both parenteral and oral therapies). [OH] I generally avoid TMP-SMX for SA osteo except for certain situations such as chronic osteo with mixed infection (SA & gram neg - all TMP-SMX sensitive). Linezolid works well but is very difficult to access oral suspension unless you promise the pharmacist your firstborn. [MS] I have only needed to use oral linezolid twice in the past 5 years, once in a patient who appeared to have hypersensitivity to PICC line plastic and who had a clindamycin-resistant MRSA confirmed by D-test, and the other in a patient with unusually severe red man syndrome also with a D-testpositive clindamycin-resistant MRSA. I think linezolid is safe and effective. Data on daptomycin are limited and thus I haven't used daptomycin at all yet for MRSA osteomyelitis. Lastly, I prefer clindamycin to Septra for MRSA joint/bone infections based on some colleagues' experience with Septra failures and have never used tetracyclines for these deep-seated infections. [CA] I was initially hesitant to use clindamycin to complete sequential IV to oral therapy, despite evidence of its efficacy with MSSA osteomyelitis. I now am more comfortable with it, although the only relapse with MRSA osteomyelitis I have ever seen occurred with this agent. I prefer not to use linezolid because I am concerned about development of resistance. [NC] Initial combination therapy with Ancef/clinda was not an option in questions. The few failures I have seen have been with vancomycin for MRSA osteo while receiving parenteral therapy, but these were only 2 patients in last 8 years. [CA] Linezolid used [only] for patients with multifocal or recalcitrant course. [AL] Re oral therapy, can't rank rifampin separately since only used in combination therapy (generally with beta-lactam or cephalosporin for MSSA). [NY] Rif usually added only for the first few days in a bacteremic patient, and always in combination with another agent with efficacy against MRSA. Someone should publish their experience with follow-on therapy with TMP-SMX; our anecdotal experience has been very favorable with many cases (no documented failures as yet). Frequently we start clindamycin in a patient who appears non-toxic and non-bacteremic. In a patient suspected to be bacteremic or who appears toxic, we start vancomycin. Clindamycin is problematic for oral therapy in small children due to the poor palatability of the suspension (horrible!). This makes the switch from iv to oral clindamycin in a patient that has improved on this empiric therapy difficult in a case of culture negative disease; one has to either switch to another agent or place a PICC, which is not without its own complications. [OR] Page 1
Rifampin used in conjunction with doxycycline in one patient. [TN] Thank you for conducting this survey. Linezolid use is rare. [GA] Typically therapy is initiated with clindamycin. Many children are culture-negative. The decision for antimicrobial choice following receipt of the negative culture results (and clinical improvement) - whether to continue clindamycin or change to a beta lactam - is unclear. We often screen with cx or PCR of nasal/skin swabs for MRSA and if negative change therapy to a beta-lactam. [NY] Use Bactrim and rifampin together if clinda resistant [MS] I have good success delivering clindamycin by layering the contents of the capsule into soft foods (chocolate sauce, jelly etc.). They seem to taste it less if the parent gives a spoonful of the soft food first, then the layered medicine, followed by another spoonful of the untainted food. For cephalexin q 6 hour dosing, most families choose 8 am, 2pm, 8 pm and 2 am dosing (they set an alarm clock). I have them condition the child to arouse slightly when the parent puts a cool, wet wash cloth on the face. The child takes the medicine, a water "chaser," and goes back to sleep without arousing completely. [OR] We debate initial therapy for children with osteomyelitis in our group. It is difficult to mandate first line drug in a not-sick child. If very sick, clearly vancomycin is one of the drugs. It would be interesting to know what others are doing. [OH] We have seen multifocal osteo with MSSA and MRSA with associated septic thrombophlebitis and myositis. If the infection is severe, usually start with vanco and rifampin or linezolid and rifampin until I know there is no inducible resistance. All of our patients have done well once changed to PO treatment. We have used TMP/Sulfa extensively as well at higher doses 20mg/kg/day div BID or TID. [FL] Complications I am impressed with the amount of venous thrombophlebitis and secondary complications we are seeing, esp with CA-MRSA; these children complete a much longer parenteral course. [TX] Would you like to know about complications from (a) prolonged high dose antibiotics and (b) PICC lines? I would like to know who manages these patients, e.g. ped I.D., adult I.D., P.C.P. or orthopedics? [DE] CA-MRSA specific comments No failures if CA-MRSA with oral therapy if get to that point (not just osteo) - use prolonged therapy, proven culture sensies for clinda, and will take it (taste is an issue for older children). [NC] Clearly staphylococcal epi has changed so that vanc & clinda have become first line empirics [TN] CA-MRSA may need to have bactericidal titer in case that unresponsive to common way of therapy such as no response in declining ESR or CRP after 7 days. [NV] Despite higher rates of CA-MRSA at body sites, most Staph osteo I have seen has been MSSA. [MD] I have not yet been unlucky to have an osteomyelitis due to CA MRSA. Currently, for a serious illness for which Staph aureus is a reasonable risk, we start linezolid and nafcillin. [WI] I think MRSA causes worse osteo than MSSA with patients sicker longer. [TX] In our recent local retrospective chart review for joint and bone infection for the last 7 years, we had only 2 cases of osteomyelitis due to CA-MRSA (one case in the last year). We will continue to collect the data to see if this incidence is going to increase. [NY] Increasing rate of MRSA, almost equaling MSSA. Children with MRSA more likely to have multiple osteo sites, endocarditis and pulmonary and CNS lesions. [OH] Page 2
My patients with CA-MRSA associated osteomyelitis are 100% more likely to require additional surgical debridement than patients with MSSA, consistent with the literature experience. [AZ] Prevalence and awareness of local susceptibility pattern of MRSA should guide empiric antimicrobial selection. Areas with high resistance to erythromycin should avoid clindamycin. I have seen increasing cases of chronic osteomyelitis because of inappropriate therapy especially the failure to drain and debride when needed. [NV] Treatment difficult for pts with clindamycin resistant MRSA. [CA] We are seeing a lot of MSSA and MRSA osteomyelitis. [OH] We have had several children in the past few yrs have difficulty clearing their infection while on parenteral therapy, both MSSA and MRSA, and this has resulted in a tendency toward a more conservative approach in general. There is variation within our group, however. [MN] We have seen a dramatic change recently: our current osteo patients have MSSA bacteremia and calcaneus osteo (2); MSSA bacteremia and acetabular osteo (1); MSSA distal phalangeal osteo (one); diaphyseal tibial osteo with pyomyositis and MSSA bacteremia (1); and necrotizing fasciitis/pyomyositis/mssa bacteremia/femur osteo/septic knee (1). At least one of these is PVL (+) MSSA (haven't checked the others). It has been several months since we had MRSA or metaphyseal long-bone osteo. [NJ] We see very few cases of CA-MRSA osteomyelitis in our hospital. We have had some quite severe MSSA osteomyelitis cases, however, with disseminated disease and requirement for prolonged antibiotic therapy. [UT] Length of IV therapy/ Switching from IV to po therapy I prefer using oral if possible once under control - main exception is neonates. [NC] Choice of antimicrobial and route is highly dependent on complicated versus uncomplicated presentation and response to therapy. [MD] The duration of IV vs PO or total course is dependent on how acute of a presentation, whether surgery was done, how long it took for there to be clinical response, whether other complications occurred. For MSSA, we probably lean towards 3-6 weeks of antibiotics for a non-complicated osteo, but for MRSA, we probably range 4-8 weeks. [CA] Hospitalists/pediatricians are quick to put in PICC lines, so I probably use more and longer parenteral treatment than I did in the past. [NC] I do not switch to oral antibiotics unless the patient has been afebrile for at least 24 hours, has a negative blood and/or pus culture on current therapy, tolerates feeds and oral medication well and parent (s) or guardian (s) appear reliable. [GA] I started peds when the treatment was 42 days of parenteral therapy in the hospital. Now, with newer data, we treat in hospital with IV antibiotics only a fraction of the time with the same, if not better, outcomes. [OH] I usually treat acute osteo a minimum of 3 weeks IV. You don't distinguish acute from chronic osteo; in the latter case we do use oral therapy for about 4.5 months after a 6 wks IV course. [IL] Many practitioners have not adapted their management of pediatric osteomyelitis in the last decade. I commonly hear the statement that patients require one or two weeks of intravenous medication, followed by "4 to 8 weeks of therapy". I believe that the key aspect of successful management of acute hematogenous osteomyelitis is individualization, based on age, type of complications present, and responses. Some patients improve rapidly and can reasonably go to oral therapy promptly (less than 7 days), while others should probably be treated orally for the entire period...and the period of appropriate therapy varies. [CA] Page 3
Once the patient has had adequate response IV, we try to switch to PO. We also encourage debridement although many times the surgeons disagree requiring us to use longer IV courses and these patients still ultimately get debridement and abscess drainage. [FL] Part of our decision making about using oral vs parenteral therapy includes how severe the infection is; e.g, severe infections are more likely to get parenteral therapy for the entire duration. [TX] The failure of oral therapy we had was an incomplete course. [CA] The one group of patients that I have run into problems with the switch from IV to oral therapy has been non-compliant adolescents. [Manitoba] There is a need for better trials of IV to po therapy switches. We also have ongoing problems with re-imbursement for oral linezolid that reduces IV to PO switches. [UT] We have been very successful with outpatient po therapy even in our population. [NY] We tend to treat longer by IV but it depends on the age of the child-the younger the child, the more likely I will treat parenterally. [NJ] We treat a large number of children with IV antibiotics for either part of course or full course (usu w/ PICC line). Parents & physicians decide whether child a candidate for po therapy. Prefer not to use po in infants <6mon of age, kids where parents say won't take meds po well (esp CA- MRSA infections) & some schoolage kids. Some school districts in GA refuse to allow kids to attend with PICC line; so, if possible, want them on po ASAP. Always give trial of po dose in hospital - saves awkward situation where pt needs to be readmitted for "unable to take or keep down po meds". May be ok to watch CRP fall to switch from IV to po but always (ALWAYS) follow WESR for treatment duration. Should have additional category for Q4: Discharged on parenteral for additional 1-2 weeks, switched to oral to complete 4-8 weeks. [GA] Oral antimicrobials ONLY after 4 weeks IV therapy [FL] I generally use parenteral therapy the whole time if multiple operations were required to drain a subperiosteal abscess since these children are the highest risk of avascular necrosis anyway. [MS] In general, since most acute hematogenous osteomyelitides occur in toddlers, I also try to avoid PICC line/home IV antibiotics whenever possible in younger children because complications of PICC lines (infection and accidental removal) are more common with younger children (e.g. a toddler whose PICC line was removed by a pet dog at home who was just playing with the child; the PICC line was not sutured, but rather taped almost securely onto the antecubital fossa with a Tegaderm dressing). [CA] Need for Data / Specific unanswered questions A question unanswered as yet is how individuals are crafting empiric therapy for AHO in children less than 3-4 who are at risk for gram-negatives. [TN] Although this is important data to gather across sites, it is likely to be highly inaccurate since it relies on memory alone without requirements for chart review, which would be very burdensome. Additionally in our practice there is some potential for overlap, duplicated numbers because of call/service rotations and required length of treatment. [AL] Has anything been studied recently re: chronic osteomyelitis therapy? [IL] I think this is an area that would benefit from a definitive study; it is very unclear the best way to manage these patients these days. [NC] I would be interested in hearing about management in culture NEGATIVE OE (much more difficult for outpatient oral transition). [CA] Very important survey for a common pediatric ID problem. Please share the results with us. [NY] We need controlled trials to know how to treat these infections. [MI] Page 4
We need more data to guide our decisions. Perhaps we should do RCT as a group. [TN] I will be presenting a poster at IDSA/ICAAC regarding 66 pediatric patients with hematogenous osteomyelitis. [CA] This survey is a great idea. We have just developed a protocol with our gen peds and ortho group to allow us to transition to PO antibiotics to reduce the PICC line complications that we frequently deal with. [FL] Other causes of osteomyelitis / culture negative cases We have seen increasing recovery of Kingella osteoarthritis in children under 3 years of age. In addition, we continue to see MSSA frequently recovered. For this reason, we are utilizing cefazolin therapy often as primary empiric therapy of children under 3 years of age. Of the total # reported, roughly 12 were trauma related. [AR] Only see immunocomp patients now, osteo is rare here and other pathogens also of concern. [MA] Most times we do not get an organism; our orthopedics do not believe in needle aspiration for culture [FL] Many are diagnosed early, have negative BC and no surgical specimen. [CO] Have seen unusual number of Gram negative chronic osteomyelitis cases related to surgery, in addition to typical cases of acute hematogenous Staph osteo. [TX] Often have great difficulty getting orthopedics to obtain a bone aspirate. Having a culture makes decisions easier. [FL] Other Issues Very few are seen at my institution nowadays, for whatever reason. Above comments represent a small sample. Cases are complicated by many different doctors involved, my approach is very simple but surgeons, ER doctors etc. complicate situations and pt usually needs to be extricated from regimens and plans started by others. [IL] Our pts have external fixators or intramedullary rods, multiple surgeries. Treatment failures: chronic osteo w/ indwelling rods. [MD] Glad you are doing this. [PA] Cannot culture K. kingae [FL] I think we miss a fair number of Kingella cases, despite culturing the synovial fluid in a Bactec blood culture bottle. Hoping for a rapid and sensitive assay (PCR?) to become commercially available. [OR] Page 5