Background
Age | Pathogens |
---|---|
< 3 months | S. aureus E. coli H. influenzae N. gonorrhoeae (in case of congenital infection) Streptococcus β haemolyticus group B C. albicans |
3 months – 5 years | S. aureus K. kingae Streptococcus β haemolyticus group A S. pneumoniae (especially under 2 years-old) H. influenzae type B (rare in fully vaccinated immunocompetent patients) |
> 5 years | S. aureus Streptococcous β haemolyticus group A N. gonorrhoeae (in sexually active adolescents) |
Methods
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antibiotic molecules for intravenous (iv) empiric therapy
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duration of intravenous antibiotic therapy
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factors influencing the switch from iv therapy to oral (os) therapy
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duration of os therapy
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total duration of antibiotic treatment
Pubmed search string
Embase search string
Inclusion criteria | Exclusion criteria |
---|---|
Subacute or acute infectious osteomyelitis due to bacterial etiology | Subacute or chronic non-infectious osteomyelitis or articles related to non-bacterial (e.g., fungal, or mycobacterial) osteomyelitis |
Osteomyelitis in children aged 28 days to 18 years-old | Osteomyelitis in patients aged < 28 days and > 18 years-old |
Uncomplicated osteomyelitis | Complicated osteomyelitis |
Osteomyelitis not caused by surgery or trauma | Osteomyelitis caused by surgery or trauma |
Osteomyelitis onset in healthy children | Osteomyelitis in children with underlying chronic, onco-hematological or immunodeficiency disorders |
Cohort studies or case reports including more of 10 patients | Guidelines |
Results
Bone penetration of antibiotics
Antibiotic | Percentage of bone penetration | ||
---|---|---|---|
Boselli 1999 [14] | Landrsdorfer 2009 [15] | Thabit 2019 [16] | |
BETA-LACTAMS | |||
Amoxicillin | 17–31% | 18–20% | 10% (amoxi-clavulanate) |
Clavulanic | – | 10–15% | – |
Ampicillin | 16% | 11–71% | – |
Sulbactam | – | 17–71% | – |
Piperacillin | 18–23% | 18–23% or 15% | 15% (piperacillin-tazobactam) |
Tazobactam | 22–26% | 22–26% | – |
Flucloxacillin | 8–15% | 5–15% | 65% |
Oxacillin | – | 11% | 21% |
CARBAPENEMS | |||
Ertapenem | – | 10–20% | 35% |
Meropenem | – | – | 50% |
CEPHALOSPORINS | |||
Ceftriaxone | – | 7–17% | – |
Cefazolin | 18% | 18% | 25% |
Cefepime | – | 46–76% | – |
Cefuroxime | 14–23% | – | – |
Cefotaxime | 8,8% | – | – |
Ceftazidime | 20–35% | 54% | 49% |
MACROLIDES | |||
Erythromycin | 28.5–39% | 18–28% | – |
Azithromycin | – | 250–630% | – |
GLYCOPEPTIDES | |||
Vancomycin | 60.8% | 5–67% | 20–40% |
Teicoplanin | 14–290% | 50–64% | – |
AMINOGLYCOSIDES | |||
Gentamicin | 14–55% | 16–33% | – |
Amikacin | 15–30% | – | – |
OTHERS | |||
Metronidazole | – | – | 50% |
Linezolida | – | 23–51% | 44% |
Daptomycin | – | 12–55% or 108% | 20% |
TMP-SMX | 11–60% | 15–50% | 25% |
Rifampicin | 17–41% | 20–25% | 40% |
Tigecyclinea | – | 35–195% or 47% | – |
Clindamycin | 98.3% | 21–45% | 26% |
Intravenous antibiotic therapy
Age | Empiric treatment (I choice) | Empiric treatment (II choice) |
---|---|---|
< 3 months | Ampicillin-sulbactam OR Cephazolin + Gentamycin | Oxacillin + Gentamycin OR Amoxicillin/clavulanate + Gentamycin OR Cefotaxime + Oxacillin (if low prevalence of ESBL) |
3 months- 5 years | Cephazolin | Amoxicillin/clavulanate OR Ampicillin/sulbactam OR Ceftriaxone + Clindamycin or Glycopeptides (if MRSA prevalence > 10%) |
> 5 years | Oxacillin OR Cephazolin OR Clindamycin | Amoxicillin/clavulanate OR Ampicillin/sulbactam OR Ceftriaxone OR Ceftazidime + Clindamycin or Glycopeptides (if MRSA prevalence > 10%) |
Antibiotic | Recommended dose |
---|---|
Amoxicillin/clavulanate | 75–100 mg/kg daily of amoxicillin in 3–4 divided doses (max 1 g/dose) |
Ampicillin/sulbactam | 100–200 mg/kg daily of ampicillin in 4 divided doses (max 2 g/dose) |
Cephazolin | 150 mg/kg daily in 3–4 divided doses (max 2 g/dose) |
Ceftazidime | 150 mg/kg daily in 3 divided doses (max 2 g/dose) |
Ceftriaxone | 50–100 mg/kg daily (max 2 g) |
Clindamycin | 45 mg/kg daily in 3 divided doses (max 900 mg/dose) |
Oxacillin | 150–200 mg/kg daily in 4 divided doses (max 2 g/dose) |
Gentamycin | neonates ≥35 weeks of gestational age: 4 mg/kg daily during the first week of life, then 5 mg/kg daily > 1 month-10 years: 8 mg/kg the first day, then 6 mg/kg daily > 10 years: 7 mg/kg daily the first day, then 5 mg/kg daily |
Linezolida | < 12 years: 30 mg/kg daily in 3 divided doses (max 600 mg/dose) > 12 years: 600 mg twice a day |
Vancomycin | 45 mg/kg daily in 3 divided doses |
Methicillin-resistant S. aureus
Panton-valentine Leukocidin–producing S. aureus
K. kingae
Oral antibiotic therapy
Age | Oral therapy |
---|---|
Unknown aetiological agent (age < 5 years)a | Cephalexin OR Amoxicillin-clavulanate +/− Rifampicin |
Unknown aetiological agent (age > 5 years) | Cephalexin OR Flucloxacillin OR Clindamycin |
S. aureus | Cephalexin OR Flucloxacillin OR Clindamycinb OR TMX-SMX + Rifampicinb OR Linezolidbc |
K. kingae | Amoxicillin-clavulanate OR Cefixime OR Cefpodoxime OR Cefazolin OR Trimethoprim/sulphamethoxazole |
S. pyogenes | Cephalexin OR Flucloxacillin OR Amoxicillin |
Antibiotic | Recommended dose |
---|---|
Cephalexin | 100 mg/kg daily in 4 divided doses (max daily dosage 4 g) |
Amoxicillin-clavulanate | 80 mg/kg daily in 3 divided doses (max daily dosage 2 g) |
Amoxicillin | 75–100 mg/kg daily in 3 divided doses (max daily dosage 3 g) |
Clindamycin | 30–40 mg/kg daily in 3–4 divided doses (max daily dosage 1.8 g) |
TMP-SMX | 8 mg/kg daily of TMP in 2 divided doses (max daily dosage 320 mg of TMP) |
Rifampicin | 10–20 mg/kg daily in 1–2 divided doses (max daily dosage 600 mg) |
Length of treatment and switch to oral therapy in AHOM
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clinical improvement (afebrile or decreasing body temperature for 24–48 h);
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improvement of local symptoms;
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lack of signs related to complication;
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30–50% decrease of CRP (compared to the peak value in the course of the infection);
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negative culture tests:
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absence of pathogens such as MRSA or PVL-SA, or other antibiotic-resistant pathogens [7].
Intravenous therapy | Proposed oral therapy |
---|---|
Cefazolin | Cephalexin |
Amoxicillin-clavulanate | Amoxicillin-clavulanate |
Ampicillin | Amoxicillin |
Ampicillin-sulbactam | Amoxicillin-clavulanate |
Oxacillin | Flucloxacillin OR Cephalexina |
Clindamycin | Clindamycin OR Trimethoprim/sulfamethoxazolea |
Ceftriaxone | Amoxicillin-clavulanate |
Ceftriaxone + Clindamycin or glycopeptides | Trimethoprim/sulfamethoxazole + Rifampicin |
Vancomycin | Trimethoprim/sulfamethoxazole + Rifampicin OR Linezolidb |
Surgical treatment
Discussion and suggestions for recommendations
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infants < 3 months of age: initial empiric use of ampicillin/sulbactam + gentamicin or cefazolin + gentamicin;
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if the prevalence of MRSA is less than 10%
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Infants and children aged 3 months to 5 years: initial empiric use of a first- or second-generation iv cephalosporin;
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Children > 5 years of age: initial empiric use of an iv anti-staphylococcal penicillin or a first- or second-generation cephalosporin or clindamycin, if the prevalence of MRSA is less than 10%;
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in case of therapeutic failure demonstrated by clinical and/or laboratory data, switch to second-line therapy (see Table 4);
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in infants and children > 3 months of age, switch to oral therapy within 5–7 days of iv therapy, after verifying the compliance of the child and the family;
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when switching from iv to oral therapy, prioritize the use of cephalexin or amoxicillin-clavulanic acid, possibly associated with rifampicin; among the anti-staphylococcal penicillin, although difficult to use due to the type of formulation that reduces its compliance, favor the use of flucloxacillin, well tolerated and with good bone penetration;
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monitor clinical signs and inflammatory biomarkers 48 to 72 h after the start of iv therapy and before switching to oral therapy (avoid switching in case of worsening of clinical conditions or increase of inflammatory biomarkers);
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in case of clinical worsening, modify iv therapy to ensure adequate coverage against resistant pathogens;
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favor the use of rifampicin and trimethoprim-sulfamethoxazole, given the good bone penetration and the optimal cost/benefit ratio; administer rifampicin in 2 daily doses, always in combination with other antibiotics, in order to avoid development of resistant strains;
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clindamycin should be used with caution due to the high prevalence of resistance in Italy (> 25%), the type of capsule formulation, and frequent gastrointestinal side effects that may reduce compliance with treatment;
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discontinue oral therapy 3 to 5 weeks after the switch if there are no complications;
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establish close clinical, laboratory, and instrumental follow-up during the administration of oral therapy and in the weeks following the complete discontinuation of therapy, possibly by a multidisciplinary team including pediatricians, an infectious disease specialist, and an orthopedics.