Severe Staphylococcal Infections Research Articles

Local Antibiotic Therapy for Osteomyelitis of a Replanted Hand

Abstract Background: Although systemic antibiotic therapy is recommended for the prevention and treatment of infection, the use of local antibiotic(s) in the setting of osteomyelitis is well established. Treatment consists of debridement and placement of antibiotics that have been added to bone cement. Hand osteomyelitis will fail periodically after treatment with systemic antibiotics. Debridement is difficult because the fine architecture of the hand limits excessive debridement that might be used in other locations. In the current study, we injected antibiotics directly into the infected bone and soft tissue and had a good result. Case Presentation: A 65-year-old man had a traumatic amputation and replantation of his right hand. He lost the majority of the skin coverage of the dorsum of the amputated hand. During treatment, his residual extensor tendons and bones had severe methicillin-resistant coagulase-negative staphylococcal (MRCNS) infection. Daily drainage and systemic antibiotics for five months ...

Rabbit Model for Superantigen-Mediated Lethal Pulmonary Disease.

Staphylococcus aureus is a highly significant cause of serious human infections in the USA. Many of these illnesses are mediated by interactions between the host immune system and staphylococcal superantigens (SAgs). Several of these severe staphylococcal infections are initiated in the lungs, making this an important site to study. Here, we describe the rabbit model for investigating the role of staphylococcal SAgs in pulmonary-associated lethal infection and intoxication.

Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia.

Th17 immunity in the gastrointestinal tract is regulated by the intestinal microbiota composition, particularly the presence of segmented filamentous bacteria (sfb), but the role of the intestinal microbiota in pulmonary host defense is not well explored. We tested whether altering the gut microbiota by acquiring sfb influences the susceptibility to staphylococcal pneumonia via induction of type 17 immunity. Groups of C57BL/6 mice which differed in their intestinal colonization with sfb were challenged with methicillin-resistant Staphylococcus aureus in an acute lung infection model. Bacterial burdens, bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels were compared between mice from different vendors, mice from both vendors after cohousing, mice given sfb orally prior to infection, and mice with and without exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb developed more severe S. aureus pneumonia than mice colonized with sfb, as indicated by higher bacterial burdens in the lungs, lung inflammation, and mortality. This difference was reduced when sfb-negative mice acquired sfb in their gut microbiota through cohousing with sfb-positive mice or when given sfb orally. Levels of type 17 immune effectors in the lung were higher after infection in sfb-positive mice and increased in sfb-negative mice after acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers of IL-22(+) TCRβ(+) cells and neutrophils in BALF. Exogenous IL-22 protected mice from S. aureus pneumonia. The murine gut microbiota, particularly the presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection.

Dramatic reduction of clindamycin serum concentration in staphylococcal osteoarticular infection patients treated with the oral clindamycin-rifampicin combination

Pharmacokinetics of clindamycin in combination with rifampicin or levofloxacin were prospectively evaluated for the oral treatment of severe staphylococcal osteo articular infections. Thirty-four patients (25 males, 9 females), with a mean age of 52.4 ± 17 years (range, 24-81 years), were randomly assigned either to the clindamycin-rifampicin or to the clindamycin-levofloxacin arm (control), following surgical debridement and intravenous adapted treatment. Trough and peak serum concentrations of clindamycin were measured at day-1 (D1), D15 and D30 of oral treatment. Cure was evaluated at a minimum of one year after the initiation of treatment. The oral treatment was interrupted in 4 cases because of adverse events. Mean trough and peak serum concentrations of clindamycin in the clindamycin-rifampicin arm were lower than in the clindamycin-levofloxacin arm during the time of oral antibiotic regimen (0.79 ± 0.3 μg/ml vs 4.7 ± 1.2 μg/ml, p < 0.001, and 3.48 ± 1.1 μg/ml vs 10.2 ± 1.8 μg/ml, p < 0.001, respectively). A consistent decrease in clindamycin serum concentration was observed at each time-point of follow-up. At a mean of 23 ± 7.8 months (range, 12-47 months), 24 patients were available for clinical evaluation. No difference could be detected in the cure rates between the groups. Our results indicate a significant influence of rifampicin on clindamycin pharmacokinetics using the oral route. Clindamycin serum concentrations (trough and peak) were systematically below the recommended therapeutic ranges when associated with rifampicin, as opposed to the control. Considering the potential risk of selection of mutant resistant to clindamycin, we do not recommend the clindamycin-rifampicin combination in the oral treatment of severe staphylococcal osteoarticular infection, unless clindamycin serum concentration is thoroughly controlled. The study has been registered on the clinicaltrials.gov website under the number NCT 01500837.

DOCK8 deficiency and guillain-barre syndrome

Results R. I. M., 10 year-old-boy that was referred to us with history of recurrent otitis media, sinusitis, and multiple episodes of pneumonia, palmo-plantar warts, and severe contagious molusco. He also has history of severe atopic dermatitis, asthma and food allergies. On evaluation he was noted to have persistent eosinophilia, lymphopenia, normal IgG levels, absent specific antibody response and decreased CD4 and CD8 T cells. Based on history of severe atopy, sinopulmonary infections, recurrent staphylococcal and viral skin infections DOCK8 deficiency was suspected. Since the suspicious, he started the use of daily cotrimazol and monthly immunoglobulin (500 mg/kg). DOCK8 gene sequencing and duplications/deletions analysis was done and there were found deletions in compound heterozygosis (Alelle 1: deletion of exons 3 to 33; Alelle 2: deletion of exons 16 and 20-24). The diagnosis was confirmed. At age 11 year, 2 weeks after a viral disease, he started a weakness involving the arms, legs, and truncal muscles, which had a rapid progression (less than 24 h). He performed an investigation with a normal magnetic resonance and the study of nerve conduction showed specific findings consistent with demyelination characteristic for classic Guilain-Barre Syndrome. He received immunoglobulin in a dose of 2g/kg and evaluated with resolution of the neurologic symptoms. Currently, he keeps receiving monthly immunoglobulin and prophylactic cotrimazol daily and showed no new serious infections. It was found a compatible bone marrow donor and he is being prepared to transplantation.

New therapeutic approach for the treatment for staphylococcal bacteremia and sepsis

Introduction. Staphylococcal bacteremia is an early and dangerous manifestation of infection, it indicates to the presence of the source of infection in the bloodstream or the dissemination ofgerms from otherfoci, is the cause of high mortality rate. In that the approaches to the treatment for bacteremia/sepsis caused by S.aureus, have surprisingly low conclusiveness and require the optimization of antibiotic therapy, duration of treatment, criteria for cure. The aim of this study was to perform the systematic analysis of the current literature devoted to the problem of antibiotic treatment for staphylococcal infection, primarily followed by bacteremia and sepsis. Objectives of the study: the detection of the problem factors having the negative impact on the effectiveness of the antibiotic treatment of severe staphylococcal infections followed by bacteremia, and prospects for the use of new antibiotics. For the solution of the designated objectives in the scientific medical databases Medscape and Pubmed there was performed the search for the publications on subject headings, covering these problems Conclusion. Bacteremia and sepsis caused by S.aureus is not uncommon and severe infection which occurs everywhere, but remains to be poorly understood. The single isolation of S.aureus from the blood always is to be considered as clinically significant due to the high pathogenicity, high probability of infection and complications, rarity of contamination of blood samples with S.aureus. In cases of the isolation of staphylococci from the blood there is required an immediate and thorough search for any focus of invasion and deep metastatic foci of infection. There are strong evidences that the removal of the origin or the drainage of the locus of infection improves the results of the treatment. There is substantially less certainty about the patients with uncomplicated infections that can receive short courses of ABT. There is discussed the optimal choice of antibiotics, the duration and method of administration for the treatment of S. aureus bacteremia (SAB). Available data indicate to the more higher efficiency of f-lactams compared with glycopeptides for the treatment for infections caused by methicillin-sensitive SAB, the emergence of glycopeptide-intermediate Staphylococcus aureus (GISA) or hetero-GISA reduces the role of glycopeptides in the treatment of bacteremia caused by MRSA. Daptomycin showed the high efficacy in the treatment for severe staphylococcal infections accompanied by bacteremia and sepsis, especially when using in a dose of 6 mg/kg/ day and above. There is insufficient data for the assertion that cephalosporins are also effective as penicillins for treating SAB, but they are probably more effective than vancomycin for the treatment of methicillinsensitive SAB. The optimal duration of treatment is considered to be 10-14 days of intravenous administration for most cases of uncomplicated SAB associated with vascular catheterization, upon condition of the removal of the catheter and low risk of endocarditis.

Prevalence of macrolide, lincosamide, and streptogramin resistance among staphylococci in a tertiary care hospital in Athens, Greece

The aims of the present study were to evaluate erythromycin, clindamycin, and streptogramin resistance rates, as well as the phenotypic and genotypic characteristics of erythromycin-resistant staphylococci in a Greek University Hospital. Macrolide, lincosamide, and streptogramin B-type resistance was investigated by double disk diffusion and the D-zone testing, while Minimal inhibitory concentration determination was performed among 656 erythromycin-resistant staphylococcal clinical consecutive isolates, too. The presence of the major genetic determinants ermA, ermB, ermC, and msrA were detected by polymerase chain reaction (PCR). The overall erythromycin resistance rate was 49·70%. One hundred and forty-six of the 322 Staphylococcus aureus were methicillin-resistant S. aureus (MRSA) (45·34%), whereas 176 were methicillin-susceptible S. aureus (54·66%). The macrolides, lincosamides, and streptogramin B-type antibiotics (MLSB)-constitutive phenotype was detected in 126 S. aureus strains (88·7%), whereas the inducible MLSB resistance phenotype was demonstrated in 16 S. aureus (11·3%). The MS phenotype was not detected. ErmC was the most frequently encountered gene responsible for macrolide resistance among S. aureus and coagulase negative staphylococci in this hospital. Pulsed-field gel electrophoresis (PFGE) analysis of SmaI DNA fragments revealed the presence of a single predominant clone among erythromycin-resistant S. aureus. The predominance of constitutive erythromycin resistance is a serious problem and limits the use of clindamycin for severe staphylococcal infections not only in this university hospital, but in many countries worldwide.

Drug repositioning: auranofin as a prospective antimicrobial agent for the treatment of severe staphylococcal infections.

Auranofin, (AF), a gold(I) complex in clinical use for the therapy of rheumatoid arthritis, is reported here to produce remarkable bactericidal effects in vitro against Staphylococcus sp. Noticeably, a similar antimicrobial action and potency are also noticed toward a few methicillin-resistant Staphylococcus aureus strains but not toward Escherichia coli. The time and concentration dependencies of the antimicrobial actions of AF have been characterized through recording time kill curves, and a concentration dependent profile highlighted. Overall, the present results point out that auranofin might be quickly and successfully repurposed for the treatment of severe bacterial infections due to resistant Staphylococci.

Multidrug-resistant bacteria: what is the threat?

Despite big advances in antimicrobial therapies and infection strategies, the emergence of antibiotic resistance represents an emergency situation, especially in immunocompromised hosts. Specifically, infections due to multidrug resistant, gram-negative pathogens are responsible for high mortality rates and may leave few effective antimicrobial options. Furthermore, although new compounds are available for severe methicillin-resistant staphylococcal infections, there is a paucity of novel classes of antimicrobials to target resistant gram-negatives. A careful assessment of the clinical conditions and underlying comorbidities, along with knowledge about the previous history of colonization or infections due to multidrug-resistant bacteria, represent key points in approaching the hematological patient with signs of infection. A de-escalation therapy with initial use of wide-spectrum antimicrobials followed by a reassessment after 72 hours of treatment may represent a good option in severe infections if a resistant pathogen is suspected. Prompt empiric or targeted therapy using combination regimens (ie, antipseudomonal beta-lactam plus an aminoglycoside or a quinolone) with the addition of colistin, along with increased dosage and therapeutic drug monitoring, represent options for these life-threatening infections. Continuous epidemiological surveillance of local bacteremias is necessary, along with stringent enforcement of antibiotic stewardship programs in cancer patients.

Topography of Distinct Staphylococcus aureus Types in Chronic Wounds of Patients with Epidermolysis Bullosa

The opportunistic pathogen Staphylococcus aureus is known to interfere with wound healing and represents a significant risk factor for wound infections and invasive disease. It is generally assumed that one individual is predominantly colonized by one S. aureus type. Nevertheless, patients with the genetic blistering disease epidermolysis bullosa (EB) often carry multiple S. aureus types. We therefore investigated whether different S. aureus types are present in individual wounds of EB patients and, if so, how they are spatially distributed. The staphylococcal topography in chronic wounds was mapped by replica-plating of used bandages and subsequent typing of S. aureus isolates. Individual chronic wounds of five patients contained up to six different S. aureus types. Unexpectedly, distinct S. aureus types formed micro-colonies that were located in close proximity and sometimes even overlapped. While some adjacent S. aureus isolates were closely related, others belonged to distinct molecular complexes. We conclude that the general assumption that one individual is predominantly colonized by one type of S. aureus does not apply to chronic wounds of EB patients. We consider this observation important, not only for EB patients, but also for other patients with chronic wounds in view of the potential risk for severe staphylococcal infections.

PHC-022 PRACTICAL USE OF THERAPEUTIC DRUG MONITORING OF TEICOPLANIN

BackgroundThe trough concentration of teicoplanin should be >10 mg/L for successful treatment, although it needs to be >20 mg/L for more severe staphylococcal infections, such as endocarditis and osteomyelitis.Purpose To...

Puffy Hand Syndrome Revealed by a Severe Staphylococcal Skin Infection

Puffy hand syndrome develops after long-term intravenous drug addiction. It is characterized by a nonpitting edema, affecting the dorsal side of fingers and hands with puffy aspect. Frequency and severity of the complications of this syndrome are rarely reported. Local infectious complications such as cellulitis can be severe and can enable the diagnosis. Herein, we report the case of a 41-year-old man who went to the emergency department for abdominal pain, fever, and bullous lesions of legs and arms with edema. Bacteriologic examination of a closed bullous lesion evidenced a methicillin sensitive Staphylococcus aureus. The abdomen computed tomography excluded deep infections and peritoneal effusion. The patient was successfully treated by intravenous oxacillin and clindamycin. He had a previous history of intravenous heroin addiction. We retained the diagnosis of puffy hand syndrome revealed by a severe staphylococcal infection with toxic involvement mimicking a four limbs cellulitis. Puffy hand syndrome, apart from the chronic lymphedema treatment, has no specific medication available. Prophylactic measures against skin infections are essential.

EComment. Early surgery for patients with uncomplicated prosthetic valve endocarditis

Attaran et al. [1] are to be commended for trying to answer an important question that recurrently arises in clinical practice: do all patients with prosthetic valve endocarditis (PVE) need surgery? The authors concluded after reviewing the relevant literature that redo surgery is warranted especially in case of complicated PVE, or when the culprit organism is Staphylococcus aureus. We entirely agree with their opinion and would like to add a brief comment concerning the timing of surgery in patients with uncomplicated PVE. Despite advances in medical and surgical care interventions, PVE remains a diagnostic and therapeutic challenge. PVE accounts for 10-30% of all cases of infective endocarditis [2], with the International Collaboration on Endocarditis, the largest registry of patients with endocarditis, reporting a PVE incidence of 20% [3]. Furthermore, the proportion of infective endocarditis cases undergoing surgery ranges from 28-42% as shown in a recent meta-analysis [4]. Unfortunately, PVE still carries a high mortality risk ranging from 20-80% of affected patients [2]. Therapeutic strategies for PVE are not backed by evidence-based recommendations. Although several retrospective studies showed that surgical intervention is indicated in cases of PVE with severe prosthetic dysfunction, heart failure, abscess formation and early staphylococcal infection, no randomized trials have been performed to examine the role of valve surgery in the management of PVE. There are no clear recommendations regarding the indication for surgery in PVE patients with uncomplicated large vegetations. Indeed, a recently published study tried to find an answer, albeit in patients with native valve endocarditis. The EASE study (Early Surgery versus Conventional Treatment in Infective Endocarditis) is a randomized control trial involving patients with native infective endocarditis, who were candidates for both early surgery and conventional treatment at two Korean medical centres [5]. They randomized 76 patients with vegetations larger than 10 mm, and severe valve dysfunction and assigned them to surgery within 48 hours after enrolment (early surgery) or to antibiotic therapy (conventional treatment). The primary end point was a composite of embolic events or death within 6 weeks after randomization. Early surgery prevented additional embolic events without increasing mortality, whereas 20% in the conventional treatment group had additional embolic events. Postponing the surgery in this patient population on the assumption that operating on them is too risky and challenging, exposes these patients to the hazard of further destruction of cardiac tissue as well as to the potential development of heart failure and embolic events, and might also render those patients ineligible for surgery due to complications of the disease or its treatment. Further randomized trials are warranted to refine the indications for and timing of surgery especially in patients with uncomplicated PVE. Conflict of interest: none declared

Safety and efficacy of daptomycin for the treatment of hospitalized adult patients in Taiwan with severe staphylococcal infections

The safety and efficacy of treating serious infections caused by Staphylococcus aureus with daptomycin in a Taiwanese population were studied. A retrospective, multicenter study was performed in Taiwan between December 2007 and June 2009. This study included adult hospitalized patients who had received intravenous daptomycin therapy for infections caused by S aureus. All patients were followed until discharge from the hospital or death. A total of 52 patients (males, n=44; median age: 62 years) were evaluated. Infections included complicated skin and soft-tissue infections (n=14), catheter-related bacteremia (n=14), osteomyelitis and septic arthritis (n=12), endovascular infections and endocarditis (n=11), and urinary tract infections (n=1). Overall, 47 (90.4%) patients were successfully treated and their clinical symptoms were resolved. Adverse effects related to daptomycin were detected in nine patients, but none were required to discontinue daptomycin. The results support daptomycin as an effective and safe treatment for staphylococcal infections in Taiwanese populations.

The MUT056399 inhibitor of FabI is a new antistaphylococcal compound.

MUT056399 is a highly potent new inhibitor of the FabI enzyme of both Staphylococcus aureus and Escherichia coli. In vitro, MUT056399 was very active against S. aureus strains, including methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), linezolid-resistant, and multidrug-resistant strains, with MIC(90)s between 0.03 and 0.12 μg/ml. MUT056399 was also active against coagulase-negative staphylococci, with MIC(90)s between 0.12 and 4 μg/ml. The antibacterial spectrum is consistent with specific FabI inhibition with no activity against bacteria using FabK but activity against FabI-containing Gram-negative bacilli. In vitro, resistant clones of S. aureus were obtained at a low frequency. All of the resistant clones analyzed were found to contain mutations in the fabI gene. In vivo, MUT056399, administered subcutaneously, protected mice from a lethal systemic infection induced by MSSA, MRSA, and vancomycin-intermediate S. aureus strains (50% effective doses ranging from 19.3 mg/kg/day to 49.6 mg/kg/day). In the nonneutropenic murine thigh infection model, the same treatment with MUT056399 reduced the bacterial multiplication of MSSA and MRSA in the thighs of immunocompetent mice. These properties support MUT056399 as a very promising candidate for a novel drug to treat severe staphylococcal infections.

Pediatric dermatology emergencies

The purpose of this review is to summarize recent advances in the diagnosis and treatment of several severe skin diseases seen in children. Several articles published recently added significantly to our understanding of drug reaction with eosinophilia and systemic symptoms (DRESS), eczema herpeticum, staphylococcal scalded skin syndrome and inherited ichthyosis. A review of 60 patients with DRESS showed 80% with hepatic involvement, 40% with renal involvement, 33% with pulmonary involvement and 50% with hematologic abnormalities. A review on eczema herpeticum describes several clinical scenarios in which it is vital to keep that diagnosis in mind. Another review on severe staphylococcal skin infections reminds us of the importance of covering for methicillin-resistant Staphylococcus aureus in all such cases until cultures and sensitivities show otherwise. The results of an international consensus conference on ichthyosis published this year will help all of us to better characterize these complicated patients. Additionally, the first case of hypothyroidism associated with a collodion baby was reported, as was the finding of an increased incidence of atypical nevi in patients with inherited ichthyosis. Although all of the conditions discussed in this article are relatively rare, it is important that they be kept on the differential diagnosis for sick infants and children with cutaneous findings, as early diagnosis and treatment of some of these conditions can be life saving.

Immunodeficiency secondary to anticytokine autoantibodies

Anticytokine autoantibodies are an important and emerging mechanism of disease pathogenesis. We will review the clinical and laboratory features of syndromes in which immunodeficiency is caused by or associated with neutralizing anticytokine autoantibodies. A growing number of patients have been described who demonstrate unique infectious phenotypes associated with neutralizing autoantibodies that target a particular cytokine known to participate in host defense against the offending organism. Examples include antigranulocyte macrophage-colony stimulating factor (GM-CSF) autoantibodies and pulmonary alveolar proteinosis; anti-interferon (IFN)-γ autoantibodies and disseminated nontuberculous mycobacteria (NTM); anti-interleukin-(IL)-6 autoantibodies and severe staphylococcal skin infection; anti-IL-17A, anti-IL-17F, or anti-IL-22 autoantibodies in patients with mucocutaneous candidiasis in the setting of both the autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED) syndrome and in cases of thymoma. Anticytokine autoantibodies have manifestations that are diverse, ranging from asymptomatic to life-threatening. These emerging and fascinating causes of acquired immunodeficiency may explain some previously idiopathic syndromes.

Fusidic acid and clindamycin resistance in community-associated, methicillin-resistant Staphylococcus aureus infections in children of Central Greece

IntroductionIn Greece, fusidic acid and clindamycin are commonly used for the empiric therapy of suspected staphylococcal infections.MethodsThe medical records of children examined at the outpatient clinics or admitted to the pediatric wards of the University General Hospital of Larissa, Central Greece, with community-associated staphylococcal infections from January 2003 to December 2009 were reviewed.ResultsOf 309 children (0-14 years old), 21 (6.8%) had invasive infections and 288 (93.2%) skin and soft tissue infections (SSTIs). Thirty-five patients were ≤30 days of age. The proportion of staphylococcal infections caused by a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate increased from 51.5% (69 of 134) in 2003-2006 to 63.4% (111 of 175) in 2007-2009 (P = 0.037). Among the CA-MRSA isolates, 88.9% were resistant to fusidic acid, 77.6% to tetracycline, and 21.1% to clindamycin. Clindamycin resistance increased from 0% (2003) to 31.2% (2009) among the CA-MRSA isolates (P = 0.011). Over the 7-year period, an increase in multidrug-resistant CA-MRSA isolates was observed (P = 0.004). One hundred and thirty-one (93.6%) of the 140 tested MRSA isolates were Panton-Valentine leukocidin-positive. Multilocus sequence typing of 72 CA-MRSA isolates revealed that they belonged to ST80 (n = 61), ST30 (n = 6), ST377 (n = 3), ST22 (n = 1), and ST152 (n = 1). Resistance to fusidic acid was observed in ST80 (58/61), ST30 (1/6), and ST22 (1/1) isolates.ConclusionIn areas with high rate of infections caused by multidrug-resistant CA-MRSA isolates, predominantly belonging to the European ST80 clone, fusidic acid and clindamycin should be used cautiously as empiric therapy in patients with suspected severe staphylococcal infections.

Successful Antibiotic Treatment of Severe Staphylococcal Infection of a Long Stent Graft in the Superficial Femoral Artery with Graft Preservation in the Long Term

Bacterial infection of endovascular stent grafts is a serious condition, regularly leading to graft replacement by open bypass surgery. We describe the case of a staphylococcal infection of a 150-mm covered stent graft (Gore Viabahn), placed in the superficial femoral artery. Stent graft infection was successfully treated by oral administration of penicillinase-resistant flucloxacillin and the lipopeptide daptomycin with complete graft preservation, not requiring surgical treatment. During 1-year follow-up, the graft infection did not reappear. However, the patient developed restenosis at the proximal margin of the stent with recurrence of mild claudication, so far treated conservatively. With the increased use of covered stent grafts in the peripheral vasculature, the frequency of graft infection will increase. We demonstrate that with newly developed antibiotics, it is possible to treat this severe complication conservatively, with complete graft preservation and without the need for bypass surgery in selected cases.

Analyses of teicoplanin concentrations from 1994 to 2006 from a UK assay service

Objectives An analysis of the trough serum concentrations sent to the UK Antimicrobial Reference Laboratory for teicoplanin therapeutic drug monitoring (TDM). Methods All trough concentrations over a 13 year period were analysed and the percentages were calculated for the following: <10 mg/L (a sub-optimal concentration for all); ≥10-<20 mg/L (the target used for ordinary Gram-positive infections); ≥20-<60 mg/L (the target for all severe staphylococcal infections including endocarditis); and ≥60 mg/L (the concentration associated with toxicity). Results The percentage of patients with concentrations of <10 mg/L decreased each year to 13% in 2006. Almost 40% of the samples each year were in the ≥10-<20 mg/L range. In 1996, the percentage of samples in the ≥20-<60 mg/L range reached a study high of ∼70%. That percentage then fell to 30% and increased slowly to 50% at the end of the study. Fewer than 5% of the samples were ≥60 mg/L. Conclusions Our study shows that there is a need to increase the initial dose or extend the number of days that the loading dose is used in a significant number of patients. With such a wide optimal range and a low potential for toxicity, it is unclear why optimal therapy is not achieved in a higher percentage of patients.