Simplifying the treatment of acute bacterial bone and joint infections in children

The treatment of acute hematogenous bone and joint infections of children – osteomyelitis (OM), septic arthritis (SA) and OM–SA combination (OM+SA) – has simplified over the past years. The old approach included months-long antibiotic treatment, started intravenously for at least a week, followed by oral completion of the course. Recent prospective randomized trials show that most cases heal with a total course of 3 weeks (OM, OM+SA) or 2 weeks (SA) of an appropriate antibiotic, provided the clinical response is good and C-reactive protein level has normalized. If the prevalence of methicillin-resistant Staphylococcus aureus and Kingella kingae is low, clindamycin and a first-generation cephalosporin are safe, inexpensive and effective alternatives. They should be administered in large doses and four times a day. Clindamycin, vancomycin and expensive linezolid are options against methicillin-resistant Staphylococcus aureus. Extensive surgery beyond a diagnostic sample by aspiration is rarely needed in uncomplicated cases.     

Anti-M in children with acute bacterial infections

Four children, 7 to 24 months old, were found to have anti-M at the time of admission to the hospital for severe acute bacterial infections. All were M−N+. Two patients had meningitis, one had septic arthritis, and the fourth had a third-degree burn of the left hand. In follow-up studies the anti-M of patients No3 and No4 were no longer detectable after 12 and 11 months respectively. In all patients no demonstrable antibody was in either maternal or cord sera at time of birth. The clinical data and bacterial isolations lead us to postulate that bacterial infections account for the formation of naturally occurring anti-M in M-negative persons.     

Antibiotic treatment of gram-positive bone and joint infections

Gram-positive organisms, particularly staphylococci and streptococci, are responsible for the majority of bone and joint infections. Treatment of these infections can be difficult, usually involving a prolonged course of antibiotics, often with surgical intervention. The selection of antibiotics depends on sensitivity profile, patient tolerance and long-term goals, e.g. cure or suppression, but there are few randomized controlled trials in patients comparing efficacy of different antibiotics. Different degrees of bone penetration and clinical outcome for specific antibiotics, e.g. the beta-lactams, clindamycin and quinolones, have been described, although the methodology in these studies is not standardized and findings cannot always be applied directly to patients. The effect of attaining minimum serum bactericidal concentrations in patients has also been studied but this is no longer routinely recommended in clinical practice. Comparative clinical trials are few but have demonstrated efficacy of oral fluoroquinolones in combination with either rifampicin or fusidic acid for selected Gram-positive infections. In the past decade, increasingly resistant organisms, e.g. methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci have been recognized as causes of orthopaedic infection. Individual case reports describe successful treatment using the newer antibiotics, e.g. linezolid and quinupristin/dalfopristin, but results of clinical trials are awaited.     

Teicoplanin in the treatment of bone and joint infections: An open study

Osteomyelitis and septic arthritis caused by Gram-positive pathogens may require prolonged inpatient treatment. The glycopeptide antibiotic, teicoplanin, can be administered once daily to outpatients, and was assessed in a multicenter, open trial in patients with such infections. Patients with proven Gram-positive osteomyelitis or septic arthritis were treated with once-daily teicoplanin, 6–12 mg/kg per day, after three loading doses at intervals of 12 h, for 4–6 weeks. A total of 342 patients were recruited, of whom 220 were fully evaluable. Surgical procedures were performed in 82% of patients. Clinical success by the end of treatment was recorded in 81/90 patients (90%) with acute osteomyelitis, 70/79 patients (88.6%) with chronic osteomyelitis, and 42/51 patients (82.4%) with septic arthritis. Four patients with acute and 4 with chronic osteomyelitis and 5 patients with septic arthritis failed to respond to treatment. Relapse was known to have occurred in 10 patients with osteomyelitis and 4 with septic arthritis. Mean trough levels of teicoplanin reached during the first week of therapy were 10 mg/l (mean dose, 6 mg/kg) and 21 mg/l (mean dose, 12 mg/kg). A mean of 75% of the treatment course was given at home. One or more adverse events were reported in 166/342 patients (48.5%), 119 (34.8%) of which were thought to be related to teicoplanin, and treatment was discontinued in 59 patients. Fever, chills, and rashes were the most common side-effects, but were usually mild. Teicoplanin was shown to be a cost-effective method of treatment of bone and joint infections caused by multiple-resistant Gram-positive pathogens. Received: February 25, 1998 / Accepted: September 9, 1998     

去甲万古霉素治疗急性革兰阳性细菌感染的疗效及安全性评价

目的 通过对去甲万古霉素治疗急性革兰阳性球菌感染疗效和安全性的观察评价，为去甲万古霉素的临床合理应用提供依据。方法 纳入急性感染患者58例，细菌培养均证实为革兰阳性细菌感染。应用国产去甲万古霉素0．4g静脉滴注．每8小时1次。分别对临床疗效、细菌学疗效和不良反应进行评价。结果 去甲万古霉素组临床有效率87．9％．细菌总清除率91．4％（其中金葡菌清除率93．5％）；不良反应发生率8．6％，主要见于高龄和原有肾脏疾病者。结论 去甲万古霉素适合于治疗急性革兰阳性细菌感染，尤其是金葡菌感染；其不良反应发生率低。高龄和原有肾脏疾病者需慎用。     

Treatment of bone, joint, and vascular-access-associated gram-positive bacterial infections with teicoplanin.

Teicoplanin, a glycopeptide antibiotic, was evaluated for safety and efficacy in the treatment of vascular-access-associated bacteremias and of bone and joint infections due to susceptible gram-positive organisms. Of 35 patients enrolled, 26 had osteomyelitis, 8 had vascular-access-associated bacteremias, and 1 had a joint infection. A total of 38 gram-positive isolates were identified: 23 Staphylococcus aureus and 6 coagulase-negative staphylococcus and 9 streptococcus isolates. After at least 6 months of follow-up, 17 patients were evaluable for efficacy: 10 of 14 (71%) with osteomyelitis and 3 of 3 with vascular-access-associated bacteremias had full resolution of their infections. Inadequate debridement, the presence of metal, and inadequate dosing were likely causes of two failures and two relapses in patients with osteomyelitis. For all but two organisms, teicoplanin MICs were less than or equal to 2 micrograms/ml. Patients who responded had median peak and trough serum bactericidal levels at serum dilutions of 1:64 and 1:16; trough levels of teicoplanin in serum were greater than 30 micrograms/ml. Patients did not respond as expected to daily doses of 4 mg/kg of body weight, which consequently were increased to greater than or equal to 15 mg/kg. Audiology testing of 20 patients found 2 with a mild loss of high-frequency hearing; 1 patient complained of tinnitus. Patients tolerated peak levels in serum as high as 127 micrograms/ml and trough levels of 49 micrograms/ml. However, 5 of 18 patients (28%) whose daily dose was greater than or equal to 12 mg/kg developed drug fever and rash and had teicoplanin discontinued. Further study of the antibiotic at such higher doses is needed.     

硫酸依替米星治疗75例急性细菌性感染

目的:评价硫酸依替米星注射液治疗急性细菌性感染的临床疗效与安全性。方法:以进口硫酸奈替米星注射液为对照药进行随机对照临床试验,共治疗住院患者95例,其中随机对照组42例(试验组22例、对照组20例)、开放组53例。硫酸依替米星与奈替米星均为每次 100 mg,q12h静脉滴注,疗程 7~10 d。结果:试验组、对照组和开放组的痊愈率与有效率分别为68.8%与90.91%、65.00%与90.00%和66.04%与084.91%。细菌清除率试验组为95.45%、对照组为100.00%、开放组为92.59%。不良反应发生率3组分别为 9.10%、5.0%和 7.55%。试验组和对照组以上各项指标比较差异均无显著性(P＞0.05)。结论:国产硫酸依替米星注射液治疗急性细菌性感染疗效确切、使用安全。     

Tedizolid for treatment of acute bacterial skin and skin structure infections

Tedizolid is a newly approved drug of the oxazolidinone class. It has high in vitro activity against Gram-positive bacteria, including multidrug-resistant strains. Peak plasma concentration of tedizolid is obtained within 3 h of oral dosing (PO), with high bioavailability. Tedizolid is mostly metabolized via the liver, and is excreted in feces in the form of a sulfate conjugate. Tedizolid 200 mg taken once daily demonstrated non-inferior efficacy and a good safety profile in patients with acute bacterial skin and skin structure infections. Results of two pivotal Phase III clinical trials showed that 6 days of 200 mg tedizolid PO or sequential intravenous (IV)/PO once-daily treatment was non-inferior to 10 days of 600 mg linezolid PO or sequential IV/PO twice-daily treatment at 48–72 h (primary end point) and at the test-of-cure in patients with acute bacterial skin and skin structure infections. The Phase II and Phase III trials also demonstrated that tedizolid was well tolerated.     

Cefoperazone versus cefamandole in the treatment of acute bacterial lower respiratory tract infections

In a randomized comparative study, 113 patients were treated with cefoperazone or cefamandole for acute bacterial lower respiratory tract infections. Most patients had Streptococcus pneumoniae or Haemophilus influenzae infections, although five patients in the cefoperazone group had infections caused by other Gram-negative bacilli (two with Pseudomonas aeruginosa). The clinical responses and adverse effects were not significantly different between the two treatment groups. Satisfactory clinical responses occurred in 36/39 (92%) of evaluable patients in the cefoperazone group and 33/34 (97%) of evaluable patients treated with cefamandole. Two failures in the cefoperazone group were secondary to superinfection (Acinetobacter and Ps. aeruginosa). Bacteriological and symptomatic failure occurred in one patient with Ps. aeruginosa lung abscess treated with cefoperazone and in one patient with a polymicrobial empyema treated with cefamandole. The results of this study indicate that cefoperazone is safe and effective in the therapy of acute bacterial lower respiratory tract infections.     

国产司帕沙星片治疗117例急性细菌性感染

目的:评价国产司帕沙星片治疗急性细菌性感染的临床疗效与安全性。方法:以国产洛美沙星片为对照药进行随机对照研究,共治疗各种细菌性感染231例,其中司帕沙星组 117例、洛美沙星组 114例。司帕沙星200~300 mg,1次/d口服,疗程 5~14 d;洛美沙星 300mg,2次/d口服,疗程 5~14 d。结果:司帕沙星组与对照组的痊愈率和有效率分别为84.62%与74.56%和 94.87%与 92.98%。细菌清除率分别为94.28%和 92.02%。组间比较差异无显著性(P＞0.05)。两组的不良反应发生率分别为7.69%和 11.40%(P＞0.05),反应多呈轻度,勿需处理可自行缓解。结论:司帕沙星抗菌谱广,抗菌活性强,为治疗中、轻度急性细菌性感染安全有效的口服抗菌药物。     

学龄前儿童急性呼吸道感染鼻咽部菌谱分析

目的了解顺德地区学龄前儿童急性呼吸道感染(ARI)鼻咽部细菌分布及耐药状况,以指导临床诊疗。方法选择2013年10月至2014年12月医院住院治疗的学龄前ARI患儿1 003例,其中急性上呼吸道感染302例,支气管炎126例,肺炎575例。采集咽拭子,进行菌种鉴定、药敏试验和统计学分析。结果 (1)该地区儿童ARI以春季好发;住院患儿肺炎感染占57.3%。(2)1 003份咽拭子分离菌株213株,阳性率为21.2%,其中革兰阴性菌和革兰阳性菌分别占53.1%、42.3%,假丝酵母菌占4.2%。(3)患儿鼻咽部病原菌检测的阳性率随着年龄的增长而降低;各年龄组检出菌谱有所差异,但均以金黄色葡萄球菌(SA)检出为首。(4)SA 100%产β-内酰胺酶,MRSA占28.8%;产ESBL的大肠埃希菌和肺炎克雷伯菌为15.4%、25.0%。结论监测期间该地区主要流行菌株是SA;学龄前儿童ARI各年龄段的细菌种类和阳性率不尽相同,临床选择抗菌药物时,应加强监测,综合考虑各种因素。     

注射用左氧氟沙星治疗急性细菌性感染的多中心随机对照研究

目的评价国产注射用乳酸左氧氟沙星治疗急性细菌性感染的临床疗效和安全性。方法采用多中心、随机、平行对照试验方法，以进口左氧氟沙星注射液（500mg／100m1）为对照药，两组的用量、用法及疗程均为500mg静脉滴注，每日1次，疗程7～14d。结果本研究共人组160例，可进行疗效分析的病例共157例，其中试验组78例，对照组79例。试验组总痊愈率和有效率分别为67．6％和89．7％。对照组总痊愈率和有效率分别为55．0％和90．0％，两组比较差异均无统计学意义（P〉0．05）。试验组细菌清除率为98．2％（53／54），对照组细菌清除率为100．0％（50／50），两组比较差异无统计学意义（P〉0．05）。试验组和对照组不良反应发生率分别为13．8％（11／80）和16．3％（13／80），主要表现为轻到中度的恶心、胃部不适、失眠、静脉炎、皮疹、转氨酶增高等，两组比较差异无统计学意义（P〉0．05）。结论国产注射用乳酸左氧氟沙星治疗呼吸系统和泌尿系统急性细菌感染，临床疗效明显，安全性较好。     

Management of bacterial infections in children with asthma

Respiratory viruses are the single most common causes of asthma exacerbations in children. Rhinovirus-induced wheezing is a risk factor for chronic asthma, but its mechanism has remained unknown. Human bocavirus is a common finding in wheezing children, but its role as a respiratory pathogen is still unclear. Mycoplasma pneumoniae may, like viruses, induce wheezing and asthma exacerbation. Chlamydia pneumoniae and, in recent studies, Chlamydia trachomatis, may not only induce asthma exacerbations but may also be involved in the pathogenesis of chronic asthma. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are often involved in respiratory infections associated with wheezing, but there is no evidence for their active role in asthma pathogenesis or exacerbation. This review summarizes current knowledge on the association between respiratory infections and asthma in children, with a special focus on the role of antibiotics in incipient asthma, asthma exacerbation and chronic stable asthma.     

Serious bacterial infections in children. When can outpatient treatment be used?

Several studies now support outpatient treatment of many serious bacterial infections in children, such as periorbital or buccal cellulitis, urinary tract infection, pneumonia, and abscess. However, an appropriate agent, that is, a third-generation cephalosporin with a long half-life, must be available and its effectiveness properly researched. In addition, children must be free of other illnesses and able to ingest fluids and maintain hydration, and their parents must be willing and able to cooperate with an outpatient treatment regimen. Family physicians can maintain the close patient and family contact needed to facilitate this form of therapy.     

Linezolid in the treatment of Gram-positive prosthetic joint infections

OBJECTIVES: To investigate the clinical efficacy and safety of linezolid in the treatment of Gram-positive prosthetic hip and knee infections. MATERIALS AND METHODS: A retrospective evaluation of patients hospitalized in the Department of Infectious Diseases of San Martino Hospital in Genoa with the diagnosis of Gram-positive prosthetic joint infection and treated with intravenous and/or oral linezolid. Primary end points were the patient clinical outcome at the end of treatment and at long-term follow-up (up to 12 months after the end of treatment). RESULTS: Between May 1999 and September 2003, 20 patients with prosthetic joint infection were treated with linezolid. Pathogens isolated were: methicillin-resistant Staphylococcus aureus (MRSA), 14 strains; methicillin-resistant coagulase-negative staphylococci, five strains; and Enterococcus spp., one strain. The overall duration of treatment was 7.2 +/- 2 weeks (range 6-10 weeks). Patients were given intravenous therapy for 3-7 days as inpatients, then were changed as outpatients to oral therapy under weekly laboratory testing. At long-term follow-up (1 year), we observed four cases of failure due to relapsing infections. The other 16 patients treated with linezolid did not need further surgical substitution of prosthesis or surgical joint revision. Linezolid was well tolerated, and no drug-related events leading to discontinuation of treatment were recorded. CONCLUSIONS: Our data indicate that linezolid may be an effective alternative therapy for orthopaedic infections caused by Gram-positive resistant pathogens and that a prospective and comparative evaluation of linezolid in this setting is necessary.