| Parenteral treatment | (Duration 0–2 weeks) Antibiotics | Alternatives |
|---|---|---|
| Staphylococcus aureus | ||
| Methicillin resistant | Vancomycin 2 × 15 mg/kg | Teicoplanin (400 mg q24h, first day q12h) |
| Daptomycin 6–10 mg/kg/d | ||
| Linezolid 2 × 600 mg/d | ||
| Methicillin susceptible | Flucloxacillin 2 g q6h | Cephalosporins of I or II generation |
| Streptococci | Penicillin G (3 Mio U q4–6h) | Cephalosporins of I or II generation |
| Gram-negatives | Ceftriaxone | Ceftazidime, cefepime |
| Anaerobes | Amoxicillin-clavulanate | Metronidazole, carbapenems, clindamycin |
| Oral treatment | (Duration 6–12 weeks) | |
|---|---|---|
| Gram-positives | Clindamycin 3 × 600 mg | Levofloxacin 2 × 500 mg |
| Trimethoprim–sulfamethoxazole 2 cp forte (2 × 960 mg) | ||
| Linezolid 2 × 600 mg | ||
| Fusidic acid 3 × 500 mg (not as monotherapy) | ||
| Gram-negatives | Ciprofloxacin 2 × 750 mg | Trimethoprim–sulfamethoxazole 2 × 960 mg |
| Levofloxacin 2 × 500 mg | ||
| Anaerobes | Metronidazole 3 × 500mg | Clindamycin 3 × 600 mg |
a Adapted from: Uçkay I, Buchs NC, Seghrouchni K, et al. Bacterial osteomyelitis: etiopathogenesis and management. In: Signore A, ed. Management of Osteomyelitis, 1st edn. Chapter 2. Rome, Italy: University of Rome; 2013:15–26.
Total duration of antibiotic therapy
In general practice, the duration of antibiotic administration is standard for most pathogens with few exceptions: pathogens for which the literature provides long-lasting antibiotic treatments (tuberculosis, other mycobacteria such as in buruli ulcer, fungi, Q fever, nocardiosis, or brucellosis). There are no clinical studies or documented records indicating the superiority of the 4- to 6-week course over shorter durations. In the retrospective study of Rod-Fleury et al., the duration of total post-debridement antibiotic treatment or its initial parenteral part only played no role on the remission incidences. One week of IV therapy had the same success as 2 to 3 weeks or more. Four weeks of total antibiotic treatment led to the same outcome as 4 to 6 weeks or more than 12 weeks. Less than 6 weeks was equal to more than 6 weeks. Haidar et al. listed small individual reports in animals and humans that obtained remission of osteomyelitis with antibiotic durations ranging from 1 to 4 weeks.
Intravenous agents
The most frequently used antibiotic agents, the β-lactam antibiotics, ubiquitously show low oral bioavailability and a low intra-osseous penetration. Since the bone penetration of vancomycin is only about 15% to 30% of the serum concentration, minimal trough serum levels of 20 to 25 mg/L are believed to treat bone infections best. In continuous perfusion, the changes in serum concentrations are much lower than in intermittent application. However, continuous perfusion does not guarantee a better outcome in terms of remission. Daptomycin depolarizes bacterial membranes and yields a rapid, dose-dependent bactericidal effect. It is only available in parenteral form and administered once a day at a dose of 6 to 8 mg/kg. This makes it suitable for an outpatient treatment. Aminoglycosides are less active in synovial fluid or in bone.
Oral agents
Linezolid can be administered orally at a dose of 600 mg BID, due to its high bioavailability of 100%. Besides an expensive price, it is associated with reversible bone marrow suppression, e.g., thrombopenia. Optic neuropathy and non-reversible peripheral neuropathy have been reported in 2% to 4% of patients with prolonged administration. A severe serotonin syndrome in co-medication with certain antidepressive drugs, such as monoamine oxidase inhibitors, has been described. TMP–SMX is an inexpensive folate antagonist. However, one reason for failure in severe osteoarticular infections might be the amount of thymidine released from damaged host tissues and bacteria. Thymidine may antagonize the antistaphylococcal effects of TMP–SMX. Hence, TMP–SMX failure may well depend on the amount of tissue damage and bacteria burden. Oral fusidic acid 500 mg tid has demonstrated efficacy in CO. Most experts do not recommend fusidic acid in monotherapy because of development of resistance. The antibiotic can be combined with rifampin. For anaerobic, streptococcal, and staphylococcal clindamycin-sensitive osteomyelitis, bacterial protein synthesis inhibition by clindamycin 600 to 900 mg TID is an option, as is metronidazole for anaerobic disease and quinolones for gram-negative infection. Pseudomonas aeruginosa and other nonfermenting gram-negative rods may rapidly develop resistance during quinolone monotherapy. Therefore, a combination with another parenteral drug for prolonged IV treatment in pseudomonal osteomyelitis would be wise, but antibiotic treatment adjusted to this situation has not been studied so far.
In acute flare-ups of CO that cannot be operated on due to various reasons (polymorbid patient, extended lesions compromising mechanical stability or gait), antibiotic therapy can aim for palliation. In these circumstances, a targeted antimicrobial therapy can be prescribed for 10 to 20 days, in order to calm down the situation, and not to cure. Hyperbaric
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