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Fosfomycin for the Initial Treatment of Acute Haematogenous Osteomyelitis N Corti, F H Sennhauser, U G Stauffer, D Nadal

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Fosfomycin for the Initial Treatment of Acute Haematogenous Osteomyelitis N Corti, F H Sennhauser, U G Stauffer, D Nadal 512 ORIGINAL ARTICLE Arch Dis Child: first published as 10.1136/adc.88.6.512 on 1 June 2003. Downloaded from Fosfomycin for the initial treatment of acute haematogenous osteomyelitis N Corti, F H Sennhauser, U G Stauffer, D Nadal ............................................................................................................................. Arch Dis Child 2003;88:512–516 Background and Aims: At our institution there has been a dichotomous antimicrobial treatment behaviour for acute haematogenous osteomyelitis (AHOM) since 1984. The surgical department favoured fosfomycin as initial choice and the medical department β lactams. We aimed to compare the performance of both strategies. See end of article for Methods: Data from patients discharged with the diagnosis of AHOM between January 1984 and authors’ affiliations January 1998 were gathered from the charts by means of a questionnaire. Patients receiving fosfomy- ....................... cin treatment (FT) were compared with those receiving fosfomycin plus other antimicrobials (FT+) and Correspondence to: those receiving no fosfomycin treatment (NFT). Dr D Nadal, Division of Results: A total of 103 patients aged 0.1–15.5 years (mean 6.5, median 6.9) with AHOM received Infectious Diseases, no surgical treatment initially. In 23 (22.3%) FT was instilled initially, in 47 (45.6%) FT+, and in 33 University Children’s (32.0%) NFT. The pathogen was established in 30%, 36%, and 42% of FT, FT+, and NFT patients, Hospital of Zurich, respectively, Staphylococcus aureus being the predominant isolate. Mean C reactive protein levels and Steinwiesstrasse 75, CH-8032 Zurich, erythrocyte sedimentation rates normalised in all treatment groups after two and four weeks, Switzerland; respectively. The mean duration of intravenous antimicrobial treatment in FT patients was 2.5 weeks, in [email protected] FT+ patients 3.1 weeks, and in NFT patients 3.8 weeks (p < 0.05), whereas the mean duration of Accepted intravenous plus oral treatment was comparable (7.1 v 6.8 v 6.5 weeks). 29 October 2002 Conclusions: The leucocyte penetrating fosfomycin performed similarly to extracellular β lactams in ....................... the treatment of AHOM. Intravenous treatment for longer than 2.5 weeks offered no advantage. cute haematogenous osteomyelitis (AHOM) is a bacte- swelling, and/or periosteal reaction, and/or bone destruction), rial infectious disease which mainly affects the paediat- and/or isolation of a pathogen from tissue puncture or ric age group. In children the yearly incidence ranges blood.4–6 Patients with concomitant arthritis, chronic osteomy- 12 A http://adc.bmj.com/ between 1:5000 and 1:10 000. These relatively low figures elitis, or osteomyelitis following a penetrating injury or hamper prospective antimicrobial treatment studies enrolling surgery were excluded. Patient data were gathered from their sufficiently large numbers of patients. Although Staphylococcus records, by means of a questionnaire containing items relating aureus is the most common identified causative agent,2 a to demography, clinical signs, diagnostic investigations, treat- further obstacle to establishment of best modalities of ment, clinical course, and outcome. anti-infective treatment is the failure to detect the causative Patients receiving fosfomycin treatment (FT) were com- organism in more than 30–50% of cases of AHOM.3 Thus, since pared with patients receiving FT plus other antimicrobial optimal antimicrobial treatment in terms of antibacterial agents (FT+) and with patients receiving antimicrobial agents compound, application route, and duration remains to be other than fosfomycin (NFT). on September 29, 2021 by guest. Protected copyright. determined, treatment modalities for AHOM practised by dif- For statistical comparison of the three treatment groups, ferent centres may vary considerably. the Mann-Whitney U test and the χ2 test were used. A p value At our institution, since 1984 the surgical and the medical <0.05 was considered statistically significant. departments have used different antimicrobial treatment regimens for AHOM. The surgical department favoured initial RESULTS intravenous treatment with fosfomycin, and the medical Study population department initial intravenous treatment with a β lactam Between January 1984 and January 1998 a total of 340 antibiotic. This dichotomous prescription behaviour within patients were discharged with the diagnosis osteomyelitis; 103 the same centre offered us the unique opportunity to compare were included in the analysis as they fulfilled the criteria for the performance of regimens containing fosfomycin, which AHOM, were beyond the neonatal age at onset of the disease, penetrates leucocytes and shows activity against a broad spec- and were initially treated conservatively. The age range was trum of bacteria, versus regimens containing β lactams. 0.1–15.5 years (mean 6.5, median 6.9). FT was installed in 23 (22%) patients, FT+ in 47 (46%), and NFT in 33 (32%). Table 1 gives a synopsis of the patients’ characteristics with PATIENTS AND METHODS respect to demography, history, clinical signs and laboratory Patients older than 1 month treated for osteomyelitis at the data on admission, and localisation of AHOM. Patients receiv- University Children’s Hospital of Zurich during the period ing FT were comparable with patients receiving FT+ or NFT, January 1984 to January 1998 were identified by computer search for the in-house code of discharge diagnosis osteomy- elitis. Only patients with community acquired AHOM and no ............................................................. primary surgical treatment were included in this analysis. Abbreviations: AHOM, acute haematogenous osteomyelitis; CRP, AHOM was defined by a history shorter than two weeks and C reactive protein; ESR, erythrocyte sedimentation rate; FT, fosfomycin the presence of two or more of the following criteria: local treatment; FT+, fosfomycin plus other antimicrobials; NFT, no fosfomycin signs of inflammation, radiological signs (deep soft tissue treatment www.archdischild.com Osteomyelitis treatment Table 1 Baseline characteristics of 103 patients with acute haematogenous osteomyelitis and no primary surgical treatment, segregated based on the initial intravenous antimicrobial treatment FT (n=23) FT+ (n=47) NFT (n=33) Characteristics Mean Median Range n % Mean Median Range n % Mean Median Range n % Demographics Age (years) 7.0 7.5 0.08–15 6.0 6.4 0.08–15.5 7.0 7.4 0.08–14.9 <2 years 5 22% 11 23% 7 21% >2 years 18 78% 36 77% 26 79% Gender Male 15 65% 29 62% 19 58% Female 8 35% 18 43% 14 42% History Duration of symptoms (days) 5 5 1–14 6 5 1–14 5 4 1–10 Closed trauma 4 17% 15 11% 5 15% Infection 8 35% 18 38% 16 48% Trauma and infection 14% 24% 1 3% Affected bones Lower limbs 10 43% 43* 91% 19 58% Clavicle, sternum, spine, pelvis 3 13% 5 11% 8 24% Upper limbs 5 22% 7 15% 7 21% Multiple 5 22% 6 13% 3 9% Clinical signs and symptoms on admission Body temperature (°C) 37.5† 37.5 36.5–39.5 23 37.9 37.7 36.5–40.1 44 38.1† 38.1 36.5–40.1 31 Erythema 4 17% 13 28% 10 30% Swelling 13 57% 26 55% 18 55% Tenderness 12 52% 29 62% 20 61% Warmth 12 52% 22 47% 13 39% Sparing 3 13% 7 15% 8 24% Limping 5 22% 11 23% 11 33% Refusal to walk 3 13% 8 17% 2 6% Decreased joint motility 8 35% 16 34% 16 48% Laboratory parameters C reactive protein (mg/l) 44.0 37.0 1–117 18 59.0 25.0 1–360 41 62.0 33.0 1–270 27 Erythrocyte sedimentation rate (mm/h) 55.0 56.5 12–116 22 49.0 46.5 3–190 40 46.0 40.5 7–138 White cell blood count (G/l) 10.0 9.7 6.5–19.7 20 11.0 10.0 4.2–31 43 12.0 11.2 4–37 31 www.archdischild.com *FT+ v FT or NFT, p<0.001. †FT v NFT, p=0.048. 513 Arch Dis Child: first published as 10.1136/adc.88.6.512 on 1 June 2003. Downloaded from from Downloaded 2003. June 1 on 10.1136/adc.88.6.512 as published first Child: Dis Arch http://adc.bmj.com/ on September 29, 2021 by guest. Protected by copyright. by Protected guest. by 2021 29, September on 514 Corti, Sennhauser, Stauffer, et al Table 2 Microbiological work up and rate of Table 3 Bacteria isolated from blood cultures or Arch Dis Child: first published as 10.1136/adc.88.6.512 on 1 June 2003. Downloaded from positive bacterial cultures cultures of bone aspirates Treatment group Initial intravenous treatment Performed cultures FT (n=23) FT+ (n=47) NFT (n=33) Isolated bacteria FT FT+ NFT From total patients 22 (96%) 43 (92%) 31 (94%) Total 7 17 14 Blood 14 (61%)†‡ 40 (85%)† 31 (94%)‡ Staphylococcus aureus 4 (57%) 11 (65%) 8 (57%) Positive 2 (14%)* 13 (33%)* 13 (42%)* Coagulase negative staphylococci 3 (43%) 3 (18%) 0 Bone aspirate 10 (44%) 16 (34%) 10 (30%) Streptococcus pyogenes 0 2 (12%) 1 (7%) Positive 5 (50%)* 6 (38%)* 4 (40%)* Streptococcus pneumoniae 0 1 (6%) 1 (7%) Blood plus bone aspirate 6 (26%) 13 (28%) 1 (3%) Haemophilus influenzae 0 0 2 (14%) Positive 0* 3 (23%)* 0* Brucella melitensis 0 0 1 (7%) Salmonella panama 0 0 1 (7%) *The percentage relates to the total number of cultures of the same material. †p=0.03; ‡p=0.003. patients and twice in two patients. The reasons were isolation except that the lower limbs were involved more often in FT+ of an organism resistant to fosfomycin (S aureus and coagulase patients than in FT or NFT patients (91% v 43% or 58%; negative staphylococci, once each), side effects (n = 5), poor p < 0.001), and the mean body temperature on admission was clinical response (n = 3), and targeted treatment after identi- higher in NFT patients than in FT patients (38.1°C v 37.5°C; fication of the causative organisms (n = 2).
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