Therapeutic efficacy of miconazole on deep-seated fungal infections in the respiratory tract system

We evaluated the therapeutic efficacy of miconazole (MCZ, Florid-F inj.), a new antifungal agent for parenteral use, in deep-seated fungal infections of respiratory tract system. A daily dose of 400-1,800 mg of MCZ was given intravenously for 12-38 days (mean: 23.4 days) to 7 patients: 2 patients with pulmonary aspergillosis, 1 patient with bronchial aspergillosis, 1 patient with pulmonary candidiasis and 3 patients with candidemia. One additional patient with pulmonary aspergillosis received three instillations of 20 mg of MCZ into the thoracic cavity. The clinical effects were excellent in 1, good in 4 and poor in 3 patients. The efficacy rate was 100% in 5 cases with respiratory fungal infections but 3 cases with candidemia did not respond well to the treatment. Four strains each of Aspergillus sp. and Candida sp. were identified as causative organisms. Seven of the 8 strains were eradicated by administration of MCZ. Side effects observed were irritation and heat in a leg in 1 patient, hyperlipoidemia in 2 patients and eosinophilia in 1 patient. The adverse reactions disappeared after the completion of the therapy. From the above results, we conclude that MCZ is one of the most useful antifungal agents for parenteral use as a first choice on deep-seated fungal infections in the respiratory tract.     

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin–clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of β-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin–clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3–12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin–clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.     

Home- versus office-based buprenorphine inductions for opioid-dependent patients

Recent legislation permits the treatment of opioid-dependent patients with buprenorphine in the primary care setting, opening doors for the development of new treatment models for opioid dependence. We modified national buprenorphine treatment guidelines to emphasize patient self-management by giving patients the opportunity to choose to have buprenorphine inductions at home or the physician's office. We examined whether patients who had home-based inductions achieved greater 30-day retention than patients who had traditional office-based inductions in a study of 115 opioid-dependent patients treated in an inner-city health center. Retention was similar in both groups: 50 (78.1%) in office-based group versus 40 (78.4%) in home-based group, p = .97. Several patient characteristics were associated with choosing office- versus home-based inductions, which likely influenced these results. We conclude that opioid dependence can be successfully managed in the primary care setting. Approaches that encourage patient involvement in treatment for opioid dependence can be beneficial.     

Invasive group A streptococcal infection: New concepts in antibiotic treatment

The incidence of severe group A streptococcal infection and the streptococcal toxic shock syndrome has increased since 1986. In contrast to earlier times, aggressive streptococal infection is now more likely to affect patients between 20 and 50 years of age who do not have predisposing underlying diseases. Its viral-like prodrome can often mislead clinicians and patients, and nonsteroidal anti-inflammatory drugs can mask symptons. Prompt antibiotic therapy is mandatory, but even with aggressive treatment mortality may be 30–50%. Though penicillin is the drug of choice for most streptococcal infections, its efficacy is poor in deep-seated soft-tissue infections, and is in part related to the in vivo inoculum effect and ‘the physiologic state of the organism’. This paper reviews the molecular mechanisms responsible for these phenomena and demonstrates the greater efficacy of clindamycin in an experimental model of severe streptococcal infection.     

Clinical studies on apalcillin in biliary tract infections (author's transl)]

Clinical studies on apalcillin (APPC), a new broad spectrum semisynthetic penicillin developed in Japan, were carried out, and the following results were obtained. APPC was administered to three patients with serious biliary tract infections by intramuscular or intravenous injection at daily dosage of 2. Therapeutic responses were excellent in all cases, and no side effects and abnormalities of laboratory findings were observed. APPC was considered to be an excellent drug for the treatment of biliary tract infections.     

A comparison of buprenorphine induction strategies: patient-centered home-based inductions versus standard-of-care office-based inductions

Although novel buprenorphine induction strategies are emerging, they have been inadequately studied. To examine our newly developed patient-centered home-based inductions, we conducted a subgroup analysis of 79 opioid-dependent individuals who had buprenorphine inductions at an urban community health center. Participants chose their induction strategy. Standard-of-care office-based inductions were physician driven, with multiple assessments, and observed, and the patient-centered home-based inductions emphasized patient self-management and included a "kit" for induction at home. We conducted interviews and extracted medical records. Using mixed nonlinear models, we examined associations between induction strategy and opioid use and any drug use. Compared with those with standard-of-care office-based inductions, participants with patient-centered home-based inductions had no significant differences in opioid use (adjusted odds ratio [AOR] = 0.63, 95% confidence interval [CI] = 0.13-2.97) but greater reductions in any drug use (AOR = 0.05, 95% CI = 0.01-0.37). Taking into account the limitations of our observational cohort study design, we conclude that participants with patient-centered home-based inductions had similar reductions in opioid use and greater reductions in any drug use than those with standard-of-care office-based inductions. It is essential that new induction strategies be based on existing models or theories and be well studied.     

Impact of Penicillin Allergy on Empirical Carbapenem Use in Gram‐Negative Bloodstream Infections: An Antimicrobial Stewardship Opportunity

Objectives

Retrospective matched‐cohort study evaluating association between penicillin allergy and empirical carbapenem use in gram‐negative bloodstream infections (BSIs) and utility of antimicrobial stewardship interventions in reducing carbapenem utilization.

Methods

Hospitalized adults with community‐onset gram‐negative BSI from January 1, 2010, to June 30, 2015, at two large community hospitals in Columbia, SC, were identified. Antimicrobial stewardship interventions targeting penicillin allergy and carbapenem utilization were fully implemented January 1, 2014. Multivariate logistic regression was used to examine impact of penicillin allergy and antimicrobial stewardship interventions on empirical carbapenem use. Kaplan‐Meier analysis was used to evaluate time to carbapenem deescalation in patients with penicillin allergy before and after interventions.

Results

Patients with penicillin allergy (n=140) were more likely to receive empirical carbapenem therapy for community‐onset gram‐negative BSI compared to those without penicillin allergy (n=140) (27% vs 12%, p=0.002). After adjustments in the multivariate model, penicillin allergy (odds ratio [OR] 3.98, 95% confidence interval [CI] 1.98–8.45) and prior β‐lactam use (OR 2.72, 95% CI 1.07–6.64) were independently associated with empirical carbapenem use, whereas antimicrobial stewardship interventions were associated with decline in carbapenem utilization (OR 0.41, 95% CI 0.16–0.94). Among patients with penicillin allergy who were prescribed empirical carbapenems, median time to carbapenem deescalation was significantly shorter in the postintervention versus preintervention period (2.0 vs 4.2 days, p=0.004).

Conclusion

Penicillin allergy was a significant contributor to carbapenem use in community‐onset gram‐negative BSI. This was subject to modification by antimicrobial stewardship interventions, which successfully reduced overall carbapenem use and duration of carbapenem therapy in patients with penicillin allergy.     

Recommendations to achieve rapid therapeutic teicoplanin plasma concentrations in adult hospitalised patients treated for sepsis

The optimum teicoplanin loading dose and duration of therapy required for rapid attainment of a therapeutic trough plasma concentration (C(min)) (> or = 10mg/L for serious Gram-positive infections and > or = 20mg/L for deep-seated infections) are not known. In this open-label, multicentre, observational study, teicoplanin levels were determined following administration of loading doses of 6 mg/kg every 12h on Day 1 followed by 6 mg/kg once or twice daily to hospitalised patients with suspected or diagnosed Gram-positive infections. C(min) levels for the first 4 days of treatment were collected 15min prior to drug administration. Levels were determined with an Abbott TDx/FLx Analyzer and Seradyn Teicoplanin Innofluor Assay Kit. The two target trough values (> or = 10mg/L and > or = 20mg/L) were only achieved by Day 4 in the once-daily group (n=34; mean 9.55 mg/L, 95% confidence interval (CI) 8.17-10.94 mg/L) and in the twice-daily group (n=40; mean 21.8 mg/L, 95% CI 17.21-26.39 mg/L), respectively. However, the mean C(min) in the twice-daily group was > or = 10mg/L (11.03 mg/L) by Day 2. To achieve rapid therapeutic C(min) concentrations targeted for the majority of serious Gram-positive infections, we recommend teicoplanin loading doses of 6 mg/kg every 12h for 48h followed by once-daily for infections other than infective endocarditis, septic arthritis and osteomyelitis. Regarding the latter infections, higher loading doses might be warranted to reach rapid steady-state concentrations.     

Comparison of 5 days of extended-release clarithromycin versus 10 days of penicillin V for the treatment of streptococcal pharyngitis/tonsillitis: results of a multicenter,double-blind,randomized study in adolescent and adult patients

OBJECTIVE: This study compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes. Research design and methods: A total of 539 patients, aged 12-75 years, were randomized to receive either clarithromycin extended-release (ER) 500 mg once daily for 5 days or penicillin V 500 mg three times daily for 10 days in this multicenter, double-blind, parallel-group trial. Eligibility required a positive antigen test for group A beta-hemolytic streptococcus (GABHS) followed by confirmatory culture. MAIN OUTCOME MEASURES: Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: study day 3; visit 3: study days 8-12; visit 4: study days 13-20; and visit 5: study days 40-50). RESULTS: At the test-of-cure visit (visit 3 for clarithromycin ER patients and visit 4 for penicillin V patients) in per-protocol patients, 5 days of clarithromycin ER was comparable to 10 days of penicillin V in eradicating S. pyogenes (89% (157/177) vs 90% (139/154) respectively; 95% CI for difference (-8.2, 5.1)). Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively; 95% CI for difference (-10.0, 4.4)). Clinical cure was achieved in > or = 94% of patients in each treatment group. The most commonly reported study drug-related adverse events (< or = 3% in either treatment group) were abdominal pain, diarrhea, dyspepsia and nausea. CONCLUSION: Clarithromycin ER 500 mg once daily for 5 days is equally effective as penicillin V 500 mg three times daily for 10 days in the treatment of adolescent and adult patients with streptococcal tonsillopharyngitis.     

Cefpodoxime proxetil. An appraisal of its use in antibacterial cost-containment programmes, as stepdown and abbreviated therapy in respiratory tract infections

Cefpodoxime proxetil is an orally administered prodrug which is converted in vivo to the third generation cephalosporin cefpodoxime. Cefpodoxime has a similar spectrum of antibacterial activity to the parenteral cephalosporins ceftriaxone and cefotaxime and a long elimination half-life, which allows once- or twice-daily administration. Cefpodoxime proxetil has proven efficacy in the treatment of community-acquired pneumonia and upper respiratory tract, skin and soft tissue and urinary tract infections. It has been evaluated for use in cost-containment programmes, as stepdown (parenteral-to-oral conversion) therapy in the treatment of community-acquired pneumonia and as abbreviated therapy in upper respiratory tract infections. Substituting oral for parenteral therapy can achieve considerable savings (in acquisition, delivery and labour costs). Moreover, oral administration has advantages for the patient in terms of comfort and mobility, avoids the hazards of parenteral delivery and may allow earlier discharge from hospital, or even allow home treatment from the outset in low-risk patients. As hospitalisation is usually the major cost component in treating serious infections, considerable savings can be made in this way. Pharmacy-driven stepdown programmes in 2 US hospitals have achieved cost savings by targeting patients with community-acquired pneumonia for early conversion from intravenous ceftriaxone therapy to oral cefpodoxime proxetil. Costs were compared with those from a control group of patients who continued to receive intravenous ceftriaxone until physicians deemed that oral therapy (with various agents) was appropriate. In one study, duration of parenteral therapy in the cefpodoxime proxetil group was reduced from 6.18 to 3.82 days and duration of hospitalisation was reduced from 10.06 to 6.23 days (p < 0.02), with corresponding hospitalisation cost reductions of $US7300 per patient. However, clinical trial data relating to the efficacy of cefpodoxime proxetil as stepdown therapy in patients initially requiring parenteral antibacterials are lacking. Abbreviated (4-to 7-day) cephalosporin regimens appear to be as effective as traditional 10-day penicillin regimens in the treatment of upper respiratory tract infections. Short regimens may improve patient compliance and tolerability, thereby reducing the costs of adverse effects and treatment failures. Data from preliminary clinical studies suggest that a 5-day course of cefpodoxime proxetil is as effective as an 8-day course of amoxicillin/clavulanic acid in treating either acute otitis media or sinusitis, and as effective as a 10-day course of amoxicillin/ clavulanic acid and more effective than a 10-day course of phenoxymethyl- penicillin in the treatment of pharyngotonsillitis. Cefpodoxime proxetil tended to be better tolerated and was associated with better compliance than penicillin-based regimens. Indeed, a pharmacoeconomic study showed that a 10-day regimen of cefpodoxime proxetil was associated with lower costs for treating adverse effects and treatment failures than a 10-day regimen of amoxicillin/clavulanic acid in the treatment of acute otitis media in children. A 5-day course of cefpodoxime proxetil had a lower cost per patient treated per month free of recurrence than a 10-day course of phenoxymethylpenicillin (non-generic) or amoxicillin/clavulanic acid in the treatment of recurrent pharyngotonsillitis. Thus, evidence to date suggests that cefpodoxime proxetil has potential for use as stepdown therapy in community-acquired pneumonia and in abbreviated therapy courses in upper respiratory tract infections. These preliminary observations require confirmation in well designed studies.     

Single dose prophylaxis in colorectal surgery

Moxalactam disodium (Latamoxef), was evaluated as a single dose prophylactic antibiotic against wound infection in open colorectal surgery. One hundred and five consecutive patients admitted to the university department of surgery, Wellington Hospital, were studied. Twelve patients were excluded because either the antibiotic was not given or antibiotics were given for other reasons. Eleven patients developed early wound infections and one further patient developed a late infection, an overall wound infection rate of 13% (95% CI 7-19). Whilst this infection rate is higher than that previously reported from this unit using more prolonged (3 dose) antibiotic prophylaxis (9.8%, 95% CI 9.6-10) the difference is not likely to be significant because the patient groups were not matched, and the comparisons were sequential. On the basis of the present study it is concluded that 1 g of moxalactam disodium administered at the induction of anaesthesia in open colorectal surgery is inexpensive, is associated with a low incidence of side effects and its further use in colorectal surgery would seem to be justified.     

Tetracycline versus penicillin in the treatment of louse-borne relapsing fever.

A prospective study of 120 louse-borne relapsing fever (LBRF) patient admitted to Mekele Regional Hospital, Tigray, Ethiopia from September to November 1991 was done. The patients were assigned systematically to a single dose of either tetracycline or procaine penicillin (sixty each). Doses given were oral tetracycline 250 mg or intramuscular procaine penicillin 200,000 units for children ages 12 years or less, and 500 mg or 600,000 IU for adults, respectively. The aim of this study was to compare the clinical effectiveness of tetracycline to that of procaine penicillin. Both drugs induced a Jarisch-Herxheimer (JH) like reaction, which was clinically similar in the two treatment groups, but peaked later and was more prolonged in the patients treated with procaine penicillin. Spirochaetes cleared more slowly and relapses were noticed only in the procaine penicillin treated group. Thus, tetracycline is recommended as first choice therapy and a single dose is sufficient for treatment of LBRF patients.     

Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of beta-lactam-resistant pneumococcal infections, the use of standard antipneumococcal beta-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, beta-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (beta-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.     

Peginterferon alfa-2a versus peginterferon alfa-2b as initial treatment of hepatitis C virus infection: a cost-utility analysis from the perspective of the Veterans Affairs Health Care System

Study Objective . To assess the cost-utility of peginterferon alfa-2a plus ribavirin, peginterferon alfa-2b plus ribavirin, and no therapy for treatment-naïve patients with chronic hepatitis C virus (HCV) infection from the perspective of the Veterans Affairs (VA) health care system by using patient-reported utility scores. Design . Cost-utility analysis using a Markov model. Setting . Veterans Affairs health care system. Data Source . Data for the model were obtained from clinical trials and published literature. Data from the VA health care system were used to define the patient cohorts. Measurements and Main Results . A Markov model incorporating transition probabilities between disease health states that depend only on the current health state was developed to simulate the progression of HCV disease. The patient cohorts were a 45-year-old male cohort and a 55-year-old male cohort, each with liver fibrosis but no cirrhosis. The lifetime expected costs, quality-adjusted life-years (QALYs) gained, and incremental net monetary benefit (INMB) with HCV treatments were determined for each cohort by genotype (genotype 1, and genotypes 2 and 3). Both peginterferon regimens were significantly more cost-effective than no treatment, although no significant differences in costs or QALYs were noted between peginterferon regimens. For the 45-year-old cohort with a genotype 1 infection, the INMB was $128,583 (95% confidence interval [CI] $79,279–$177,308) and $128,025 (95% CI $80,425–$173,448) versus no treatment for peginterferon alfa-2a plus ribavirin and peginterferon alfa-2b plus ribavirin, respectively. Treatment with either peginterferon regimen produced significantly lower lifetime HCV-related medical costs for genotype 2 or 3 infections, but not genotype 1. Conclusions . Peginterferon alfa-2a plus ribavirin and peginterferon alfa-2b plus ribavirin were found to be cost-effective treatments for patients with HCV infections, particularly with genotypes 2 and 3. However, no significant differences in costs or efficacy were observed between these peginterferon treatment regimens.     

Comparison of 5 days of extended-release clarithromycin versus 10 days of penicillin V for the treatment of streptococcal pharyngitis/tonsillitis: results of a multicenter,double-blind,randomized study in adolescent and adult patients

SUMMARY

Objective: This study compared a short-course of clarithromycin with a standard course of penicillin V in patients with tonsillopharyngitis caused by Streptococcus pyogenes.

Research design and methods: A total of 539 patients, aged 12–75 years, were randomized to receive either clarithromycin extended-release (ER) 500?mg once daily for 5 days or penicillin V 500?mg three times daily for 10 days in this multicenter, double-blind, parallel-group trial. Eligibility required a positive antigen test for group A beta-hemolytic streptococcus (GABHS) followed by confirmatory culture.

Main outcome measures: Bacteriological and clinical assessments were conducted at each study visit (visit 1: study day 1; visit 2: study day 3; visit 3: study days 8–12; visit 4: study days 13–20; and visit 5: study days 40–50).

Results: At the test-of-cure visit (visit 3 for clarithromycin ER patients and visit 4 for penicillin V patients) in per-protocol patients, 5 days of clarithromycin ER was comparable to 10 days of penicillin V in eradicating S. pyogenes (89% (157/177) vs 90% (139/154) respectively; 95% CI for difference (?8.2, 5.1)). Bacterial eradication was sustained in both treatment groups at the follow-up visit (88% (135/153) vs 91% (112/123) respectively; 95% CI for difference (?10.0, 4.4)). Clinical cure was achieved in > 94% of patients in each treatment group. The most commonly reported study drug-related adverse events (< 3% in either treatment group) were abdominal pain, diarrhea, dyspepsia and nausea.

Conclusion: Clarithromycin ER 500?mg once daily for 5 days is equally effective as penicillin V 500?mg three times daily for 10 days in the treatment of adolescent and adult patients with streptococcal tonsillopharyngitis.     

2013-2017 年我院化脓性链球菌儿童株耐药模式及其感染特点分析

目的 了解化脓性链球菌(Streptococcus pyogenes, SP) 在儿童中的致病谱及其耐药特点。方法 回顾性分析我院 2013-2017 年细菌培养为SP 的患儿的临床特点。结果 分离到SP 的患儿514 例，其中6 例同时在咽拭子和阴道分泌物中培养 出SP。407 株(79.2%) 来自阴道分泌物，91 株(17.7%) 来自呼吸道标本，无菌标本10 株(1.9%)，其他标本12 株(2.3%)。患儿年龄 (7.02±2.26) 岁。侵袭性感染10 例。所有菌株对青霉素、头孢曲松和万古霉素敏感，青霉素MIC50和MIC90分别为0.023 和0.048μg/ mL；98.4% 的菌株对左氧氟沙星敏感，对红霉素、克林霉素耐药率分别为94.6% 和93%。2 例化脓性脑膜炎患儿发生脑梗塞、 脑瘫后遗症。结论 SP 主要引起儿童呼吸道和外阴阴道感染，青霉素和头孢曲松可作为该菌感染的首选用药，局部使用左氧氟 沙星可作为SP 外阴阴道炎的基础治疗。     

A controlled intervention study to improve antibiotic use in a Russian paediatric hospital

A controlled intervention study was performed in a paediatric hospital in Russia to improve antibiotic use and to see whether improvements persisted. During October–December 2002, clinical and microbiological data, antibiotic use, costs and outcome were recorded at two wards for gastrointestinal infections (GIIs) and two wards for respiratory tract infections (RTIs). Guidelines for diagnosis and treatment of infections were developed and implemented at one ward for GIIs and one ward for RTIs in 2003. The other two wards served as controls. The same data were recorded during the same 3-month periods in 2003 and 2004. At the intervention ward, the percentage of patients with GII who received antibiotics decreased from 94% in 2002 to 41% in 2003, but increased to 73% in 2004. In RTI patients these percentages were 90% in 2002, 53% in 2003 and 83% in 2004. The proportions of patients who received antibiotics in 2004 were still lower than in 2002: risk difference (RD) = 0.217 (P ≤ 0.001) in GIIs and RD = 0.073 (P = 0.013) in RTIs. From 2002 to 2004 there was a decrease in cephalosporin use (P = 0.021) and an increase in penicillin use (P = 0.032) in pneumonia. There was no difference in mortality, duration of fever or duration of hospital stay between the intervention and control wards. Antibiotic use could be halved without compromising the quality of patient care, but 1 year after the intervention the use of antibiotics approached pre-intervention levels. Strategies to sustain the effect of interventions are needed.     

Penicillin and clindamycin differentially inhibit the production of pyrogenic exotoxins A and B by group A streptococci.

Streptococcal pyrogenic exotoxins A (SPE-A) and B (SPE-B) have been implicated in the pathogenesis of serious group A streptococcal infections including streptococcal toxic shock-syndrome. Current antibiotics used for the treatment of these infections are penicillin and clindamycin. The effects of sub- and suprainhibitory concentrations of penicillin and clindamycin were evaluated in 14 isolates of Streptococcus pyogenes that were fully susceptible to both antibiotics. Clindamycin was superior to penicillin in reducing the production of SPE-A and SPE-B by invasive and non-invasive Dutch group A streptococcal isolates in vitro.     

Tick-borne infections in children: epidemiology, clinical manifestations, and optimal management strategies

Ticks can transmit bacterial, protozoal, and viral infections to humans. Specific therapy is available for several of these infections. Doxycycline is the antimicrobial treatment of choice for all patients, regardless of age, with Rocky Mountain spotted fever, human monocytic ehrlichiosis, or human granulocytic ehrlichiosis. Chloramphenicol has been used to treat these infections in children but is demonstrably inferior to doxycycline. In patients with Mediterranean spotted fever, doxycycline, chloramphenicol, and newer macrolides all appear to be effective therapies. Therapy of Lyme disease depends on the age of the child and stage of the disease. For early localized disease, amoxicillin (for those aged <8 years) or doxycycline (for those aged >/=8 years) is effective. Doxycycline, penicillin V (phenoxymethylpenicillin) or penicillin G (benzylpenicillin) preparations, and erythromycin are all effective treatments for tick-borne relapsing fever. Hospitalized patients with tularemia should receive gentamicin or streptomycin. Doxycycline and ciprofloxacin have each been investigated for the treatment of tularemia in outpatients; however, these agents do not yet have established roles in the treatment of this disease in children. Combination therapy with clindamycin and quinine is preferred for children with babesiosis; the combination of azithromycin and atovaquone also appears promising. Ribavirin has been recently shown to markedly improve survival in patients with Crimean-Congo hemorrhagic fever. The role of antiviral therapy in the treatment of other tick-borne viral infections, including other hemorrhagic fevers and tick-borne encephalitis, is not yet defined.