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Repeated serum alkaline phosphatase measurements in the treatment of childhood acute bone and joint infections with high doses of antibiotics.

Pääkkönen M, Kallio MJ, Kallio PE, Peltola H - Ann Lab Med (2013)

View Article: PubMed Central - PubMed

Affiliation: Division of Diseases of the Musculoskeletal System, Turku University Hospital and University of Turku, Turku, Finland. Markus.Paakkonen@helsinki.fi

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Levels of serum alkaline phosphatase (ALP) and the hepatic enzyme ALT are used to monitor medication toxicity... The serum concentration of bone-specific ALP reflects the cellular activity of osteoblasts, and ALP elevation is encountered during bone formation or increased bone turnover... Furthermore, high ALP concentrations are found under septic conditions... However, on day 19, ALP levels were significantly higher among Hib patients; the mean±SEM value was 620±52 IU/L compared to those with Staphylococcus aureus (483±21 IU/L) or Streptococcus pyogenes (387±17 IU/L) disease (P=0.84, 0.68, 0.61, <0.05, and 0.87 on days 1, 2, 10,19, and 29, respectively)... ALT levels increased beyond the cut-off value in 6 patients but normalized during the follow-up in all patients, and no patients developed liver or kidney failure... In a recent in vitro study, clindamycin stimulated cell metabolism of human osteoblasts at low concentrations and had cytotoxic effects at higher levels (i.e., 500 µg/mL)... A first-generation cephalosporin (cefazolin) has been found to decrease osteoblast replication at 200 µg/mL and cause cell death at concentrations exceeding 10,000 µg/mL... The in vivo concentrations are remarkably reduced; for instance, the cefazolin concentration normally seen in patients who have osteomyelitis and are receiving intravenous cefazolin is 5-13 µg/mL in pus and 3-5 µg/g in bone... The antibiotic treatment was changed in only 2 cases of extreme ALP elevation... Administering exceptionally large doses of reliable time-honored antibiotics proved to be a safe and effective strategy in these potentially severe infections... In the current series, there were no significant differences in the ALP levels in patients with bone involvement, probably because BAP represents less than one-fourth of the total ALP concentration... The patients were enrolled prospectively, and no equally large dataset is available yet for pediatric bone and joint infections... Our results show that, despite the exceptionally high doses of antibiotics used in this study, major elevations in ALP are rare and have no detectable correlation with adverse events... Minor ALP elevation is common in bone and joint infections and does not necessitate treatment alteration.

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(A) Alkaline phosphatase levels in patients with osteomyelitis (N=106) versus patients with septic arthritis (N=134). (B) Alkaline phosphatase levels in patients given clindamycin (N=99) versus first-generation cephalosporin (N=70).Abbreviation: ALP, alkaline phosphatase.
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Figure 1: (A) Alkaline phosphatase levels in patients with osteomyelitis (N=106) versus patients with septic arthritis (N=134). (B) Alkaline phosphatase levels in patients given clindamycin (N=99) versus first-generation cephalosporin (N=70).Abbreviation: ALP, alkaline phosphatase.

Mentions: Staphylococcus aureus was the most common causative organism (75%, 199/265), followed by Hib (10%, 26/265), Streptococcus pyogenes (9%, 25/265), and Streptococcus pneumoniae (5%, 12/265). The median age was 8 yr (interquartile range, 4-11 yr). No child developed septic shock. The ALP levels on days 1, 2, 10, 19, and 29 were 415±13, 368±14, 344±18, 487±18, and 510±17 IU/L (mean±standard error of mean [SEM]), respectively. ALP levels for osteomyelitis (N=106) and septic arthritis (N=134) did not differ significantly (P=0.15, 0.95, 0.86, 0.66, and 0.73 on days 1, 2, 10, 19, and 29 respectively; Fig. 1). In osteomyelitis combined with septic arthritis (N=25), the ALP level was 346±34 and 422±44 IU/L on days 1 and 29, respectively. High ALP levels, exceeding 750 IU/L (range, 758-939 IU/L), on admission, were noted in 3 patients. ALP concentrations did not differ between clindamycin (N=99) and cephalosporin (N=70) recipients (P=0.18, 0.25, 0.09, 0.81, and 0.61 on days 1, 2, 10, 19, and 29, respectively). Data were similar for Hib patients treated with ampicillin or amoxicillin on days 1, 2, 10, and 29. However, on day 19, ALP levels were significantly higher among Hib patients; the mean±SEM value was 620±52 IU/L compared to those with Staphylococcus aureus (483±21 IU/L) or Streptococcus pyogenes (387±17 IU/L) disease (P=0.84, 0.68, 0.61, <0.05, and 0.87 on days 1, 2, 10,19, and 29, respectively). The mean serum creatinine levels were 55±1, 51±2, 53±1, 52±1, and 54±1 µmol/L (range, 17-88, 24-94, 28-103, 23-87, and 17-91 µmol/L, respectively) on days 1, 2, 10, 19, and 29, respectively. No cases of kidney failure were observed. Two clindamycin recipients developed a rash.


Repeated serum alkaline phosphatase measurements in the treatment of childhood acute bone and joint infections with high doses of antibiotics.

Pääkkönen M, Kallio MJ, Kallio PE, Peltola H - Ann Lab Med (2013)

(A) Alkaline phosphatase levels in patients with osteomyelitis (N=106) versus patients with septic arthritis (N=134). (B) Alkaline phosphatase levels in patients given clindamycin (N=99) versus first-generation cephalosporin (N=70).Abbreviation: ALP, alkaline phosphatase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756246&req=5

Figure 1: (A) Alkaline phosphatase levels in patients with osteomyelitis (N=106) versus patients with septic arthritis (N=134). (B) Alkaline phosphatase levels in patients given clindamycin (N=99) versus first-generation cephalosporin (N=70).Abbreviation: ALP, alkaline phosphatase.
Mentions: Staphylococcus aureus was the most common causative organism (75%, 199/265), followed by Hib (10%, 26/265), Streptococcus pyogenes (9%, 25/265), and Streptococcus pneumoniae (5%, 12/265). The median age was 8 yr (interquartile range, 4-11 yr). No child developed septic shock. The ALP levels on days 1, 2, 10, 19, and 29 were 415±13, 368±14, 344±18, 487±18, and 510±17 IU/L (mean±standard error of mean [SEM]), respectively. ALP levels for osteomyelitis (N=106) and septic arthritis (N=134) did not differ significantly (P=0.15, 0.95, 0.86, 0.66, and 0.73 on days 1, 2, 10, 19, and 29 respectively; Fig. 1). In osteomyelitis combined with septic arthritis (N=25), the ALP level was 346±34 and 422±44 IU/L on days 1 and 29, respectively. High ALP levels, exceeding 750 IU/L (range, 758-939 IU/L), on admission, were noted in 3 patients. ALP concentrations did not differ between clindamycin (N=99) and cephalosporin (N=70) recipients (P=0.18, 0.25, 0.09, 0.81, and 0.61 on days 1, 2, 10, 19, and 29, respectively). Data were similar for Hib patients treated with ampicillin or amoxicillin on days 1, 2, 10, and 29. However, on day 19, ALP levels were significantly higher among Hib patients; the mean±SEM value was 620±52 IU/L compared to those with Staphylococcus aureus (483±21 IU/L) or Streptococcus pyogenes (387±17 IU/L) disease (P=0.84, 0.68, 0.61, <0.05, and 0.87 on days 1, 2, 10,19, and 29, respectively). The mean serum creatinine levels were 55±1, 51±2, 53±1, 52±1, and 54±1 µmol/L (range, 17-88, 24-94, 28-103, 23-87, and 17-91 µmol/L, respectively) on days 1, 2, 10, 19, and 29, respectively. No cases of kidney failure were observed. Two clindamycin recipients developed a rash.

View Article: PubMed Central - PubMed

Affiliation: Division of Diseases of the Musculoskeletal System, Turku University Hospital and University of Turku, Turku, Finland. Markus.Paakkonen@helsinki.fi

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Levels of serum alkaline phosphatase (ALP) and the hepatic enzyme ALT are used to monitor medication toxicity... The serum concentration of bone-specific ALP reflects the cellular activity of osteoblasts, and ALP elevation is encountered during bone formation or increased bone turnover... Furthermore, high ALP concentrations are found under septic conditions... However, on day 19, ALP levels were significantly higher among Hib patients; the mean±SEM value was 620±52 IU/L compared to those with Staphylococcus aureus (483±21 IU/L) or Streptococcus pyogenes (387±17 IU/L) disease (P=0.84, 0.68, 0.61, <0.05, and 0.87 on days 1, 2, 10,19, and 29, respectively)... ALT levels increased beyond the cut-off value in 6 patients but normalized during the follow-up in all patients, and no patients developed liver or kidney failure... In a recent in vitro study, clindamycin stimulated cell metabolism of human osteoblasts at low concentrations and had cytotoxic effects at higher levels (i.e., 500 µg/mL)... A first-generation cephalosporin (cefazolin) has been found to decrease osteoblast replication at 200 µg/mL and cause cell death at concentrations exceeding 10,000 µg/mL... The in vivo concentrations are remarkably reduced; for instance, the cefazolin concentration normally seen in patients who have osteomyelitis and are receiving intravenous cefazolin is 5-13 µg/mL in pus and 3-5 µg/g in bone... The antibiotic treatment was changed in only 2 cases of extreme ALP elevation... Administering exceptionally large doses of reliable time-honored antibiotics proved to be a safe and effective strategy in these potentially severe infections... In the current series, there were no significant differences in the ALP levels in patients with bone involvement, probably because BAP represents less than one-fourth of the total ALP concentration... The patients were enrolled prospectively, and no equally large dataset is available yet for pediatric bone and joint infections... Our results show that, despite the exceptionally high doses of antibiotics used in this study, major elevations in ALP are rare and have no detectable correlation with adverse events... Minor ALP elevation is common in bone and joint infections and does not necessitate treatment alteration.

Show MeSH
Related in: MedlinePlus