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Background: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs)., Methods: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated., Results: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics., Conclusions: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis., Competing Interests: Potential conflicts of interest. C. T. P. reports a grant from Bayer for a randomized study, and a grant from Novo Nordisk for an epidemiological study. L. K. reports payment for speaking engagements from AstraZeneca, Bayer, Boehringer, and Novartis. C. M. reports payment for speaking engagements from AstraZeneca, GSK, MSD, and Pfizer; co-authorship of the Danish Treatment Guidelines for Infective Endocarditis and of the ESCMID guidelines for prevention, treatment and diagnosis of biofilm infections; and service as a board member of the European Society for Clinical Microbiology Study Group (ESCMID) for Biofilms (ESGB). E. L. F. reports grants from Novo Nordisk Foundation and the Danish Heart Association. N. E. B. reports grants from Novo Nordisk Foundation, Health Insurance Denmark, and Augustinus Foundation (all unrelated to this study). F. S. R. reports unpaid positions on the Danish Ministry of Health's National expert advisory board on antimicrobial stewardship, the Region of Southern Denmark's Regional working group on antimicrobial stewardship, and chairman on the Steering committee and working group at Odense University Hospital for rational use of antimicrobial drugs. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Recent evidence has shown that oral antibiotic therapy is not inferior to IV antibiotic therapy in the treatment of complicated Staphylococcus aureus infections. Therefore, oral antibiotic therapy is now frequently prescribed in clinical practice due to cost benefit, ease of administration, decreased complication rate, and lack of need for IV access. In vitro susceptibility testing for β-lactam oral antibiotics is not routinely performed as the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI) recommend using oxacillin and cefoxitin as surrogate markers. Hence, oral antibiotic susceptibilities for cephalexin and dicloxacillin are not reported and implied based on oxacillin and cefoxitin. The objective of the current study was to determine whether susceptibilities among S. aureus isolates are predictable when comparing commonly used IV and oral beta-lactams., Methods: Cefazolin, cephalexin, dicloxacillin, and oxacillin broth microdilution minimum inhibitory concentrations (MICs) were determined for 100 clinical isolates of methicillin-sensitive S. aureus by broth microdilution following CLSI guidelines., Results: Among these isolates, median MICs for cephalexin were eight-fold higher than cefazolin MICs and median MICs for dicloxacillin were four-fold less than oxacillin MICs. Ten percent of more strains studied had a major or very major error in its susceptibility reporting when cephalexin was compared to its surrogate marker oxacillin., Discussions/conclusions: The variations in MICs observed compounded with the dosing and pharmacokinetic differences of oral versus IV β-lactam suggests that establishing breakpoints for oral β-lactam antibiotics is necessary to ensure adequate therapy is selected for the treatment of complex S. aureus infections., (© 2022 S. Karger AG, Basel.)

Background: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear., Objectives: To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy., Methods: We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables., Results: A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]., Conclusions: Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Dicloxacillin is a beta-lactam antibiotic that is commonly used in the treatment of lactational mastitis in breastfeeding women. Although penicillins have long been considered safe for breastfeeding mothers and their infants, there is almost no data on the transfer of dicloxacillin into human breast milk despite the fact that it is commonly used for mastitis. Case Report: This study determined the drug concentration-time profile of dicloxacillin in milk samples collected from three lactating mothers consuming 500 mg dicloxacillin taken every 6 hours for treatment of mastitis. Milk levels were measured using liquid chromatography mass spectrometry. The maximum concentration of dicloxacillin in milk was 67.6 ng/mL. The relative infant dose (RID) was calculated to be 0.03%. This value is well below the theoretical level of concern of 10%. Discussion: The limited transfer of dicloxacillin into human milk is probably explained by the high plasma protein binding of dicloxacillin and its subsequent poor penetration into human milk. Conclusion: In this case series, the level of dicloxacillin in milk was found to be very low, and the RID to be only 0.03% of the maternal dose. Although the levels detected were low, dicloxacillin does transfer into breast milk. Caution should be exercised in infants with hypersensitivity to penicillins.

We have previously shown that the phenothiazine, thioridazine, acts in synergy with the beta-lactam antibiotic, dicloxacillin, to kill methicillin-resistant Staphylococcus aureus. In this study, we investigated whether synergy by combining these two drugs could also be observed in vancomycin intermediate susceptible S. aureus (VISA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Synergy was observed in three of four tested VISA strains, suggesting that the thickening of cell wall does not interfere with the effects of thioridazine. In S. epidermidis, no synergy was observed in all tested strains, suggesting that synergy by combining thioridazine and dicloxacillin is isolated to S. aureus species.

Introduction: Conservative treatment solutions against aortic prosthetic vascular graft infection (APVGI) for inoperable patients are limited. The combination of antibiotics with antibacterial helper compounds, such as the neuroleptic drug thioridazine (TDZ), should be explored., Aim: To investigate the efficacy of conservative systemic treatment with dicloxacillin (DCX) in combination with TDZ (DCX+TDZ), compared to DCX alone, against early APVGI caused by methicillin-sensitive Staphylococcus aureus (MSSA) in a porcine model., Methods: The synergism of DCX+TDZ against MSSA was initially assessed in vitro by viability assay. Thereafter, thirty-two pigs had polyester grafts implanted in the infrarenal aorta, followed by inoculation with 106 CFU of MSSA, and were randomly administered oral systemic treatment with either 1) DCX or 2) DCX+TDZ. Treatment was initiated one week postoperatively and continued for a further 21 days. Weight, temperature, and blood samples were collected at predefined intervals. By termination, bacterial quantities from the graft surface, graft material, and perigraft tissue were obtained., Results: Despite in vitro synergism, the porcine experiment revealed no statistical differences for bacteriological endpoints between the two treatment groups, and none of the treatments eradicated the APVGI. Accordingly, the mixed model analyses of weight, temperature, and blood samples revealed no statistical differences., Conclusion: Conservative systemic treatment with DCX+TDZ did not reproduce in vitro results against APVGI caused by MSSA in this porcine model. However, unexpected severe adverse effects related to the planned dose of TDZ required a considerable reduction to the administered dose of TDZ, which may have compromised the results.

The widespread emergence of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically eroded the efficacy of current β-lactam antibiotics and created an urgent need for new treatment options. We report an S. aureus phenotypic screening strategy involving chemical suppression of the growth inhibitory consequences of depleting late-stage wall teichoic acid biosynthesis. This enabled us to identify early-stage pathway-specific inhibitors of wall teichoic acid biosynthesis predicted to be chemically synergistic with β-lactams. We demonstrated by genetic and biochemical means that each of the new chemical series discovered, herein named tarocin A and tarocin B, inhibited the first step in wall teichoic acid biosynthesis (TarO). Tarocins do not have intrinsic bioactivity but rather demonstrated potent bactericidal synergy in combination with broad-spectrum β-lactam antibiotics against diverse clinical isolates of methicillin-resistant staphylococci as well as robust efficacy in a murine infection model of MRSA. Tarocins and other inhibitors of wall teichoic acid biosynthesis may provide a rational strategy to develop Gram-positive bactericidal β-lactam combination agents active against methicillin-resistant staphylococci., (Copyright © 2016, American Association for the Advancement of Science.)

Background: It is well known that obesity complicates the course of several diseases. However, it is unknown whether obesity affects the risk of infection among healthy individuals., Methods: We included 37,808 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. Obesity was defined as a body mass index ≥ 30 kg/m(2). Infections among participants were identified by relevant ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical (ATC) codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis with age as the underlying timescale was used as the statistical model., Results: During 113,717 person-years of observation, 1,233 participants were treated for infection at a hospital. Similarly, during 58,411 person-years of observation, 15,856 participants filled at least one prescription of antimicrobials. Obesity was associated with risk of hospital-based treatment for infection (women: hazard ratio [HR] = 1.5, 95% confidence interval [CI] = 1.1, 1.9; men: HR = 1.5, 95% CI = 1.2, 1.9). For specific infections, obesity was associated with increased risk of abscesses (both sexes), infections of the skin and subcutaneous tissue (men), and respiratory tract infections and cystitis (women). Similarly, obesity was associated with filled prescriptions of antimicrobials overall (women: HR = 1.22, 95% CI = 1.14, 1.30; men: HR = 1.23, 95% CI: 1.15, 1.33) and particularly with phenoxymethylpenicillin, macrolides, dicloxacillin and flucloxacillin, and broad-spectrum penicillins., Conclusions: In a large cohort of healthy individuals, obesity was associated with risk of infection. This result warrants further studies of metabolism and the immune response.

Diffuse large B-cell lymphoma (DLBCL) associated with chronic inflammation is a recently adopted category of DLBCL, which describes an aggressive B-cell lymphoma raised in the setting of non-immune chronic inflammation. Primary presentation of this subtype of DLBCL in bone is extremely rare. Here, we present the case of a 27 year old woman with DLBCL of the right distal femur, identified after a three-year history of chronic osteomyelitis. In this report, we describe the clinical and histopathologic features of this unusual presentation of DLBCL and discuss aspects relevant to diagnosis and treatment of this entity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: The objective of the present study was to compare the efficacy of cefuroxime with that of dicloxacillin as definitive antimicrobial therapy in methicillin-susceptible Staphylococcus aureus bacteraemia (MS-SAB) using a Danish bacteraemia database, information on the indication for antimicrobial therapy, multivariate adjustment and propensity score (PS) matching., Methods: This was a retrospective cohort study. MS-SAB cases from 1 January 2006 to 31 December 2008 were included from a total of seven hospitals in the greater Copenhagen area and seven hospitals in the North Denmark Region. Information including demographics, antimicrobial therapy and clinical condition was obtained. The physician's note detailing the indication for starting empirical antimicrobial therapy was given special attention. Hazard ratios (HRs) and 95% CIs for 30 day and 90 day mortality were calculated using PS-adjusted Cox proportional hazards regression analyses. In addition, PS matching was performed., Results: A total of 691 patients with MS-SAB received either dicloxacillin (n = 368) or cefuroxime (n = 323) as definitive antimicrobial therapy. Twenty-eight different indications for empirical antimicrobial therapy were identified and grouped into eight categories. There was no statistically significant difference in 30 day mortality between the two groups (HR 1.02, 95% CI 0.68-1.52). Definitive antimicrobial therapy with cefuroxime was associated with increased 90 day mortality in a PS-adjusted multivariate analysis (HR 1.43, 95% CI 1.03-1.98) and in the PS matching (OR 1.65, 95% CI 1.06-2.56). Antimicrobial therapy for an indication of 'severe infection' was independently associated with 90 day mortality (HR 1.97, 95% CI 1.19-3.28)., Conclusions: Definitive antimicrobial therapy with cefuroxime was associated with significantly higher 90 day mortality than was dicloxacillin therapy in patients with MS-SAB.

Objectives: Penicillin-susceptible Staphylococcus aureus isolates account for a fifth of cases of S. aureus bacteraemia (SAB) in Denmark, but little is known about treatment outcomes with penicillins or other antimicrobials. Here we compare penicillin, dicloxacillin and cefuroxime as definitive treatments in relation to 30 day mortality., Methods: A retrospective chart review of 588 penicillin-susceptible S. aureus cases at five centres from January 1995 to December 2010. Data on demographics, antimicrobial treatment, clinical signs and symptoms, and mortality at day 30 were collected. Hazard ratios (HRs) with 95% CIs associated with mortality were modelled using propensity-score-adjusted Cox proportional hazards regression analysis. Propensity-score-matched case-control studies were carried out., Results: Definitive therapy with cefuroxime was associated with an increased risk of 30 day mortality compared with penicillin (adjusted HR 2.54, 95% CI 1.49-4.32). Other variables that were statistically significantly associated with 30 day mortality included increasing age, disease severity and a primary respiratory focus. Osteomyelitis/arthritis was associated with a lower risk of death than were other secondary manifestations. Propensity-score-matched case-control studies confirmed an increased risk of 30 day mortality: cefuroxime treatment (39%) versus penicillin treatment (20%), P = 0.037; and cefuroxime treatment (38%) versus dicloxacillin treatment (10%), P = 0.004., Conclusions: Definitive therapy for penicillin-susceptible SAB with cefuroxime was associated with a significantly higher mortality than was seen with therapy with penicillin or dicloxacillin.

This paper estimates the price elasticity of demand for prescription drugs using an exogenous shift in consumer co-payment caused by a reform in the Danish subsidy scheme for the general public. Using purchasing records for the entire Danish population, I show that the average price response for the most commonly used drug yields demand elasticities in the range of -0.36 to -0.5. The reform is shown to affect women, the elderly, and immigrants the most. Furthermore, this paper shows significant heterogeneity in the price response over different types of antibiotics, suggesting that the price elasticity of demand varies considerably even across relatively similar drugs., (Copyright © 2012 John Wiley & Sons, Ltd.)

Introduction: Subcutaneous trunk abscesses are frequent, and current treatment options generally involve incision. By contrast, the standard care for breast abscesses is ultrasound-guided drainage. The aim of this study was to evaluate the feasibility of ultrasound-guided drainage combined with antibiotics in the treatment of subcutaneous abscesses on the trunk., Material and Methods: In this prospective study, 27 patients were treated with ultrasound-guided needle aspiration and oral antibiotics. Follow-up was performed at a 3-6-day interval, and the procedure was repeated if the abscess was not obliterated., Results: Treatment was initially successful in 25 of the 27 participants (93%); two patients went on to surgery. The median time from first treatment to the final control visit was nine days. The 25 patients with initial successful treatment were contacted after a median of 84 days, and six (24%) of these reported recurrence of an abscess at the puncture site. 88% of the patients reported that they were satisfied or very satisfied with ultrasound-guided drainage., Conclusion: Our results indicate that ultrasound-guided drainage combined with antibiotics is feasible in the treatment of small subcutaneous abscesses on the trunk. Ultrasound-guided drainage was well-tolerated, had a high degree of success and short healing times. Additional randomised studies are needed to verify our findings., Funding: not relevant., Trial Registration: not relevant.

Deep brain stimulation (DBS) is being used to treat an increasing number of movement and psychiatric disorders. However, the risk of infection remains as a problem that can hinder the usefulness of this technology. We report a case of a patient with dystonia who underwent bilateral globus pallidus interna electrode and impulse generator (IPG) placement, developed an infection of his IPG, and later cerebritis. The patient was initially treated with antibiotics and partial hardware removal. Follow-up cranial imaging showed an area concerning for cerebritis around one of the intracranial electrodes. The patient was then treated with complete hardware removal followed by a course of intravenous antibiotics. Four-month follow-up imaging showed resolution of the infection. This case demonstrates the importance of following cranial imaging in DBS patients with delayed infection, continued vigilance for infection in implanted patients and that partial hardware removal may not be successful in the setting of methicillin-sensitive Staphylococcus aureus infections.

We compared the activity of dicloxacillin with that of vancomycin against 15 oxacillin-susceptible, methicillin-resistant Staphylococcus aureus (OS-MRSA) clinical isolates. By population analyses, we found that 6 OS-MRSA isolates were able to grow in the presence of up to 8 μg/ml dicloxacillin and 9 isolates were able to grow in 12 to >32 μg/ml dicloxacillin; all isolates grew in up to 2 μg/ml vancomycin. Both drugs exhibited similar bactericidal activities. In experimental infections, the therapeutic efficacy of dicloxacillin was significant (P < 0.05 versus untreated controls) in 10 OS-MRSA isolates and vancomycin was effective (P < 0.05) against 12 isolates; dicloxacillin had an efficacy that was comparable to that of vancomycin (P > 0.05) in 8 isolates. The favorable response to dicloxacillin treatment might suggest that antistaphylococcal penicillins could be used against OS-MRSA infections.

The small-colony-variant (SCV) phenotype of Staphylococcus aureus has been associated with difficult-to-treat infections, reduced antimicrobial susceptibility, and intracellular persistence. This study represents a detailed intra- and extracellular investigation of a clinical wild-type (WT) S. aureus strain and its counterpart with an SCV phenotype both in vitro and in vivo, using the THP-1 cell line model and the mouse peritonitis model, respectively. Bacteria of both phenotypes infected the mouse peritoneum intra- and extracellularly. The SCV phenotype was less virulent and showed distinct bacterial clearance, a reduced multiplication capacity, and a reduced internalization ability. However, some of the SCV-infected mice were still culture positive up to 96 h postinfection, and bacteria of this phenotype could spread to the mouse kidney and furthermore revert to the more virulent WT phenotype in both the mouse peritoneum and kidney. The SCV phenotype is therefore, despite reduced virulence, an important player in S. aureus pathogenesis. In the THP-1 cell line model, both dicloxacillin (DCX) and linezolid (LZD) reduced the intracellular inocula of bacteria of both phenotypes by approximately 1 to 1.5 log(10) in vitro, while DCX was considerably more effective against extracellular bacteria. In the mouse peritonitis model, DCX and LZD were also able to control both intra- and extracellular infections caused by either phenotype. Treatment with a single dose of DCX and LZD was, however, insufficient to clear the SCVs in the kidneys, and the risk of recurrent infection remained. This stresses the importance of an optimal dosing of the antibiotic when SCVs are present.

Background: Juvenile recurrent parotitis (JRP) is a rare salivary gland disease of obscure aetiology that affects children. It is characterized by multiple episodes of unilateral or bilateral parotid inflammation over a period of years., Case Report: A 14 year old boy presented with multiple episodes of recurrent bilateral swellings of the parotid glands since 1 year of age with no relevant past medical and dental history,, Treatment: Included prescription of antibiotic Dicloxacillin 500 mg tid for 7 days and analgesics as a combination of Diclofenac 50 mg and Paracetamol 500 mg tid for 10 days, to resolve acute infection followed by sialography using Iopromide (ultravist-300) twice at an interval of 6 months for glandular lavage which helps to clear the mucous plugs that form during the acute phase., Follow-Up: It was satisfactory as there has been no recurrence of parotitis during 18 months.

We describe a case of a 10 year old boy who developed an contact dermatitis to black henna tattoo. Sixteen days later he was brought to the emergency department because of an presumed superinfection by S. aureus. The infection was successfully treated with dicloxacillin and the allergic reaction with bethametasone ointment and tablets. The use of pure henna is legal but has been proven to be harmful in animal experiments. Para-phenylendiamine (PPD) has been mixed with henna to achieve a darker colour and to decrease the treatment time and is well known to cause allergic reactions.

Purpose: This study was conducted to evaluate early diagnosis, clinical course, and treatment outcome in children with pyomyositis., Methods: Between 2001 and 2006, 6 children with a mean age of 7.2 years were diagnosed and treated for pyomyositis in our clinic. The most common site of involvement was the hip and thigh region. All patients underwent early magnetic resonance imaging (MRI) examination that played a significant role in the early diagnosis and management of the disease., Results: Staphylococcus aureus was the most common pathogen and was identified in 3 cases. Intravenous antibiotics were administered and were followed by oral agents for an additional period. The duration of therapy ranged from 3 to 6 weeks. No surgical intervention was needed. Magnetic resonance imaging was used to evaluate response to the therapy., Conclusions: Although pyomyositis is a rare disease, it should be considered in the differential diagnosis of immediate onset of musculoskeletal pain in children. Early diagnosis and antibiotic treatment are important as major complications such as abscess formation and sepsis can be avoided. Having a high sensitivity to reactive inflammatory changes, MRI is a valuable tool in the armamentarium of the clinician in early diagnosis of pyomyositis.

Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response to therapy and the high frequency of infection recurrence. The intracellular persistence of staphylococci has been recognized and could offer a good explanation for these treatment difficulties. Knowledge of the interplay between intracellular antibiotic activity and the overall outcome of infection is therefore important. Several intracellular in vitro models have been developed, but few experimental animal models have been published. The mouse peritonitis/sepsis model was used as the basic in vivo model exploring a quantitative ex vivo extra- and intracellular differentiation assay. The intracellular presence of S. aureus was documented by electron microscopy. Five antibiotics, dicloxacillin, cefuroxime, gentamicin, azithromycin, and rifampin (rifampicin), were tested in the new in vivo model; and the model was able to distinguish between their extra- and intracellular effects. The intracellular effects of the five antibiotics could be ranked as follows as the mean change in the log(10) number of CFU/ml (Delta log(10) CFU/ml) between treated and untreated mice after 4 h of treatment: dicloxacillin (3.70 Delta log(10) CFU/ml) > cefuroxime (3.56 Delta log(10) CFU/ml) > rifampin (1.86 Delta log(10) CFU/ml) > gentamicin (0.61 Delta log(10) CFU/ml) > azithromycin (0.21 Delta log(10) CFU/ml). We could also show that the important factors during testing of intracellular activity in vivo are the size, number, and frequency of doses; the time of exposure; and the timing between the start of infection and treatment. A poor correlation between the intracellular accumulation of the antibiotics and the actual intracellular effect was found. This stresses the importance of performing experimental studies, like those with the new in vivo model described here, to measure actual intracellular activity instead of making predictions based on cellular pharmacokinetic and MICs.

Objective: To evaluate the quality of care for mastitis managed by telephone without an office or emergency room visit., Study Design: A word search of electronic medical records allowed for identification of patients managed with a mastitis clinical practice guideline. Comparisons of outcomes were made to a group of patients who received care in the clinic, urgent care or emergency room., Results: Rates of successful resolution with 1 encounter were 86% for telephone-based care and 82% for visit-based care (p = 0.550). Antibiotic selection was enhanced by use of the standing order., Conclusion: Telephone-based management of mastitis may be safe, effective, and efficient.

Background: Endocarditis is a common complication in Staphylococcus aureus bacteremia (SAB). We compared risk factors, clinical manifestations, and outcome in a large, prospective cohort of patients with S. aureus endocarditis in injection drug users (IDUs) and in nonaddicts., Methods: Four hundred and thirty consecutive adult patients with SAB were prospectively followed up for 3 months. Definite or possible endocarditis by modified Duke criteria was found in 74 patients: 20 patients were IDUs and 54 nonaddicts., Results: Endocarditis was more common in SAB among drug abusers (46%) than in nonaddicts (14%) (odds ratio [OR], 5.12; 95% confidence interval [CI], 2.65-9.91; P < 0.001). IDUs were significantly younger (27 +/- 15 vs 65 +/- 15 years, P < 0.001), had less ultimately or rapidly fatal underlying diseases (0% vs 37%, P < 0.001) or predisposing heart diseases (20% vs 50%, P = 0.03), and their SAB was more often community-acquired (95% vs 39%, P < 0.001). Right-sided endocarditis was observed in 60% of IDUs whereas 93% of nonaddicts had left-sided involvement (P < 0.001). An extracardiac deep infection was found in 85% of IDUs and in 89% of nonaddicts (P = 0.70). Arterial thromboembolic events and severe sepsis were also equally common in both groups. There was no difference in mortality between the groups at 7 days, but at 3 months it was lower among IDUs (10%) compared with nonaddicts (39%) (OR, 5.73; 95% CI, 1.20-27.25; P = 0.02)., Conclusion: S. aureus endocarditis in IDUs was associated with as high complication rates including extracardiac deep infections, thromboembolic events, or severe sepsis as in nonaddicts. Injection drug abuse in accordance with younger age and lack of underlying diseases were associated with lower mortality, but after adjusting by age and underlying diseases injection drug abuse was not significantly associated with mortality.

Purpose: To report the uncommon occurrence of impetigo contagiosa in the setting of recurrent staphylococcal conjunctivitis., Design: Interventional case report., Methods: A 32-year-old patient had a recurrent painful red left eye and facial rash. Clinical examination revealed left bacterial conjunctivitis and facial bullous impetigo. Microbiology cultures were taken from the nose, conjunctiva, and facial lesions., Results: Microbiologic cultures grew Staphylococcus aureus, and hematology findings demonstrated an elevated white cell count with neutrophilia. Complete resolution was achieved with topical chloramphenicol ointment and oral dicloxacillin., Conclusions: Although uncommon, bullous impetigo may be associated with recurrent staphylococcal conjunctivitis in adults. Recurrent infections may require nasal decolonization, systemic antibiotics, and antiseptic body wash.

A 52-year-old black woman presented with a 2-day history of lower lip swelling 5 days after starting a new medication, lisinopril. She had never experienced similar episodes in the past. She denied shortness of breath, tightening of the throat, swelling of the tongue, generalized cutaneous eruption, urticaria, or pruritus. She also denied symptoms consistent with facial paresis. Her past medical history was significant for hepatitis C infection, coronary artery disease, and hypertriglyceridemia. She had a 15 pack-year smoking history and denied both alcohol and drug abuse. She had never received a blood transfusion and was HIV negative. Physical examination disclosed a tender, swollen, and erythematous lower lip with induration, oozing, and crusting (Figure 1). Pinpoint openings evident throughout the lip surface exuded a clear, sticky, mucoid secretion. Tongue, parotid glands, and regional lymph nodes were normal. The working diagnosis was angioedema secondary to lisinopril. The presumptive offending drug was discontinued, and conservative therapy (topical clobetasol ointment, oral ranitidine, and oral fexofenadine) was initiated. Despite treatment, signs and symptoms persisted unabated. One week after initial presentation, a punch biopsy of her lower lip was taken to rule out granulomatous cheilitis and sarcoidosis. Histopathology included diffuse lymphohistiocytic infiltrate, minimal microabscess formation, and notable absence of granulomata. There was neither hypertrophy nor detectable abnormality of the salivary glands, with the exception of infiltrating mononuclear cells. Based on the clinical history and compatible pathologic findings, a diagnosis of cheilitis glandularis was made. Specifically, crusting and erosion clinically suggested a diagnosis of the superficial suppurative subtype of cheilitis glandularis. The patient received oral penicillin (dicloxacillin, 1.0 g/d) combined with oral fluoroquinolone (ciprofloxacin, 1.0 g/d). Within 2 weeks of starting the antibiotics, the lip swelling significantly decreased (Figure 2) and the patient was left with a mildly indurated nodule at the labial commissure. Following a 4-week course of continued antibiotic treatment, the lip returned to near baseline state. At both 6-month and 1-year follow-up visits, the lip remained normal.

In a controlled field trial, 178 dairy cows with chronic endometritis and at least 21 days in lactation were randomly assigned to four different treatment groups: prostaglandin F2alpha intramuscularly (PG, 5 mg dinoprost (5 ml Dinolytic), n = 51), intrauterine antibiotics (AB; 400 mg ampicillin + 800 oxacillin (20 ml Totocillin), n = 49), intrauterine antiseptics (AS; 100 ml 4% Lotagen, n = 50); control (C, no initial treatment, n = 28). Before treatment, uterine swabs for bacteriologic examination and blood samples for determination of serum progesterone concentrations were collected. Two weeks following the first treatment, cows were reexamined. In case no clinical cure was diagnosed, treatment was repeated and control cows were treated for the first time with one of the three treatments mentioned above. The four treatment groups did not differ with respect to the clinical cure or reproductive performance. Therefore, factors that might have an influence on clinical cure and fertility were evaluated. With increasing duration of lactation, the clinical cure after a single treatment increased significantly over all treatment groups from 59.5% (treatment before day 42 postpartum) to 79.6% (treatment following day 42 postpartum) (P < 0.05). Within the PG group, a statistically significantly higher cure rate after a single treatment and first service conception rate and a lower pregnancy index were obtained when the treatment was performed following day 42 postpartum (P < 0.05). This was not the case in the other treatment groups. A retarded involution of the uterus based on the size had a negative effect on clinical cure over all groups (first treatment clinical cure: 68.2% (small uteri) vs 44.4% (large uteri); P < 0.05). Within groups, this effect was also detected, but only as a trend (P > 0.05). Isolation of Arcanobacterium (A.) pyogenes negatively influenced first treatment clinical cure over all treatment groups (79.0% vs 31.5%) and within treatment groups (P < 0.05). In the AB group, the pregnancy index, days open and the interval from first insemination to conception increased compared with the other treatment groups, when A. pyogenes was detected. Isolation of unspecific bacteria and the presence or absence of a corpus luteum only had minor effects over all and within the PG, AS and C group. Within the AB group, presence of luteal tissue was connected with a higher pregnancy index and increased days open and interval from first insemination to conception (P < 0.05). A multivariate analysis revealed that the presence of A. pyogenes and no initial treatment (control group) had a statistically significant independent and negative influence on the first treatment clinical cure. Ill-smelling vaginal discharge and no treatment had a negative independent effect on first service conception rate. Furthermore, days open were negatively influenced by the interval from calving to first examination and the presence of ill-smelling vaginal discharge. In conclusion, under the conditions of this field study, it seems preferrable to treat chronic endometritis. However, under the condition of a herd health program with continuous observation of sick and healthy animals, a wait-and-see attitude might also be justified.

Background: Sternal wound infections remain a major cause of morbidity after cardiac surgery. Vancomycin is often the only effective antibiotic available for their treatment but its use for routine prophylaxis is inadvisable for ecological reasons. Local application of gentamicin produces high antibiotic concentrations in the wound. We aimed to determine whether this treatment could have an additive effect on the incidence of sternal wound infections when combined with routine prophylaxis., Methods: Two thousand cardiac surgery patients were randomized to routine prophylaxis with intravenous isoxazolyl-penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure. Endpoint was any sternal wound infection within 2 months postoperatively. Evaluations were double-blind and made on an intention-to-treat basis., Results: Evaluation was possible in 967 and 983 patients in the control and treatment groups, respectively. The incidence of sternal wound infection was 4.3% in the treatment group and 9.0% in the control group (relative risk 0.47; 95% confidence interval 0.33-0.68; p < 0.001). Early reoperation for bleeding was more common in the treatment group (4.0% vs 2.3%, p = 0.03). No difference in postoperative renal function was noted., Conclusions: Local collagen-gentamicin reduced the risk for postoperative sternal wound infections. Further studies are warranted to confirm these results, particularly with regard to deep infections.

A case is presented of an aviator with frequent dermatologic lesions concerning for recurrent furunculosis that was caused by community-acquired methicillin-resistant Staphylococcus aureus. The presentation, diagnosis, treatment, and aeromedical disposition of recurrent furunculosis are discussed.

Background: Staphylococcus aureus bacteremia is still a serious problem, and the optimal treatment is under debate. Only a few studies concerning treatment are available., Methods: The study population was all patients with a positive blood culture result for S aureus in Copenhagen County, Denmark, from May 1994 through April 1996. Of 278 patients with S aureus bacteremia, 186 were evaluated according to outcome in a prospective, observational follow-up study. The time above the minimum inhibitory concentration was estimated for dicloxacillin sodium for each treatment regimen and evaluated by logistic regression along with other potential risk factors., Results: The following variables were statistically associated with death: the presence of an uneradicated focus (odds ratio [OR], 6.7; 95% confidence interval [CI], 2.1-21.0); the presence of septic shock (OR, 3.7; 95% CI, 1.5-9.1); the total daily dose of penicillinase-stable penicillin less than 4 g (OR, 3.7; 95% CI, 1.3-11.1); and age 60 years or older (OR, 2.4; 95% CI, 1.1-5.3). The following variables were significantly associated with recurrence: the total daily dose of penicillinase-stable penicillin less than 3 g (OR, 3.9; 95% CI, 1.6-10.0) and the presence of a secondary focus (OR, 3.2; 95% CI, 1.3-7.7). Among 155 patients with observation time longer than duration of treatment, this factor (duration of treatment, <14 days) was significantly related to mortality (OR, 0.84; 95% CI, 0.76-0.94)., Conclusions: Focus eradication and the dosing of penicillinase-stable penicillin are important to the outcome of S aureus bacteremia. We recommend treatment with at least 1 g of penicillinase-stable penicillins 4 times daily for longer than 14 days.

The aim of this study was to evaluate the efficacy of cefuroxime, compared with the combination of dicloxacillin/chloramphenicol, for the treatment of children with parapneumonic pleural effusion or empyema. Forty patients, aged 3 months to 5 years, with pleural effusion or empyema were randomized to receive cefuroxime (100 mg/kg/day) IV (n=20) or chloramphenicol (100 mg/kg/day) plus dicloxacillin (200 mg/kg/day) IV (n=20). Both groups were similar in age, days of illness, clinical and radiological findings, and etiology. Most patients (70%) had an empyema at presentation. There was no difference in clinical outcomes, including days to defervescence, duration of respiratory distress, duration of chest tube drainage, and days to discharge from hospital. The complication rates were similar in both groups. Pleural thickening occurred in four patients, bronchopleural fistula in two, and loculated empyema in one patient of each treatment group. Adverse effects attributed to cefuroxime were mild and infrequent. These results suggest that cefuroxime is an effective and well-tolerated alternative for the treatment of children with pleural effusion and empyema., (Copyright 2002 Elsevier Science Ltd.)

This randomized, double-blind, multicenter trial compared the efficacy and safety of linezolid, an oxazolidinone, with those of oxacillin-dicloxacillin in patients with complicated skin and soft tissue infections. A total of 826 hospitalized adult patients were randomized to receive linezolid (600 mg intravenously [i.v.]) every 12 h or oxacillin (2 g i.v.) every 6 h; following sufficient clinical improvement, patients were switched to the respective oral agents (linezolid [600 mg orally] every 12 h or dicloxacillin [500 mg orally] every 6 hours). Primary efficacy variables were clinical cure rates in both the intent-to-treat (ITT) population and clinically evaluable (CE) patients and microbiological success rate in microbiologically evaluable (ME) patients. Safety and tolerability were evaluated in the ITT population. Demographics and baseline characteristics were similar across treatment groups in the 819 ITT patients. In the ITT population, the clinical cure rates were 69.8 and 64.9% in the linezolid and oxacillin-dicloxacillin groups, respectively (P = 0.141; 95% confidence interval -1.58 to 11. 25). In 298 CE linezolid-treated patients, the clinical cure rate was 88.6%, compared with a cure rate of 85.8% in 302 CE patients who received oxacillin-dicloxacillin. In 143 ME linezolid-treated patients, the microbiological success rate was 88.1%, compared with a success rate of 86.1% in 151 ME patients who received oxacillin-dicloxacillin. Both agents were well tolerated; most adverse events were of mild-to-moderate intensity. No serious drug-related adverse events were reported in the linezolid group. These data support the use of linezolid for the treatment of adults with complicated skin and soft tissue infections.

We studied fecal colonization with vancomycin-resistant enterococci (VRE) in 89 HIV-infected nonhospitalized patients ages 24 to 62 years, including 70 (79%) men (including 41 homosexual and 5 bisexual men) and 19 (21%) women. Of the 89 patients, 61 (69%) were black, 25 (28%) Hispanic, and 3 (3%) white; 53 (60%) had history of ongoing or recent antibacterial therapy with trimethoprim/sulfamethoxazole (29), clarithromycin (18), amoxicillin (7), ofloxacin (3), and metronidazole, doxycycline, dicloxacillin, and cephalexin (1 each). VRE were not isolated from any of the patients studied.

Background and Objectives: Delayed breast cellulitis is an infrequently reported entity after conservation therapy for breast cancer. We describe our experience with this entity at Naval Medical Center, San Diego., Methods: Eight patients who presented with delayed cellulitis after wide local excision/axillary dissection and breast radiotherapy (RT) are presented. Their clinical characteristics and therapy are described and possible causative factors are analyzed., Results: The latency of breast cellulitis is variable after breast conservation therapy, although most cases in our experience and in the literature occur within a year post-RT. These infections are frequently refractory to a single course of antibiotics (n = 4 cases in our experience). Some patients suffer multiple episodes separated by months., Conclusions: Breast cancer patients are at risk for delayed cellulitis after conservative surgery and RT. The mechanism of such events probably involves lymph stasis, however, therapy is no different from the more frequently occurring cases of cellulitis presenting perioperatively.

Elephantiasis nostras (EN) is a clinical entity that usually presents as a persistent swelling of the lower extremities. It has been related to recurrent lymphangitis of bacterial origin that causes a fibrosis and thickening of both epidermal and connective tissue. Although very rare, EN has been previously reported in the lips. This is the first case reported in the oral medicine literature that describes EN involving the lips. We describe the clinical features and a differential diagnosis of the lip lesions and a treatment protocol to which this patient has responded. A diagnosis of EN should be entertained in patients with chronically edematous, scaling lip lesions.

Two children with staphylococcal blistering distal dactylitis (BDD), a condition usually caused by streptococci, are reported. Etiologic distinction in BDD can be made only bacteriologically. Staphylococci are increasingly the cause of bacterial cutaneous infections.

The approach to patients with chronic cough has been well defined and evaluated in the literature through a number of prospective studies. Meticulous attention to detail of the afferent loop of the cough reflex has helped identify the cause of cough in most patients. The most common causes appear to be similar in both children and adults and include asthma, postnasal drip syndromes, gastroesophageal reflux diseases, and aspiration. In children, recurrent viral infections and infections with atypical organisms also are very prevalent. Specific therapy directed at the cause alleviates the cough in most patients. In some patients, there may be more than one cause of cough. Invasive testing (eg, bronchoscopy and esophageal pH probing) is rarely necessary. In patients in whom a specific cause cannot be identified or in whom cough modifiers are necessary while specific therapy is taking hold, antitussives of both the narcotic and nonnarcotic variety are helpful.

Debate continues concerning proper management of peritonsillar abscess (PA). We studied 189 children (mean age, 9 years) admitted in our department during the last 7 years with the diagnosis of PA. Management consisted of incision and drainage (performed in 92.5% of the children without general anaesthesia) and antibiotic therapy intravenously. There was resolution without complications in the overwhelming majority of the cases. After the initial episode, we further followed up 101 children. The recurrence rate was 15.8%. Forty-seven percent of the recurrences occurred 1 month after the children had been discharged. Probably some of these second PA should be considered as persistent and not as recurrent. Therefore, we propose that after their discharge, the children must take oral antibiotics (resistant to beta-lactamase) for more than 10 days. Cultures were taken from 58 cases. The predominant bacterial isolates were Streptococcus spp. (55%), anaerobes spp. (12%) and Staphylococcus aureus (6%). To our knowledge, this is the first survey that addresses exclusively a pediatric population and suggests that incision and drainage without general anaesthesia is an applicable and effective management in children with PA. Moreover, we believe that peritonsillar abscess is no longer a strong indication for tonsillectomy due to the relatively low rate of recurrence. We recommend close follow-up, mainly for the first months after the initial episode.