A retrospective analysis to estimate trough concentrations of teicoplanin in patients with suspected or documented Gram-positive infections

Abstract Teicoplanin is a glycopeptide antibiotic commonly used to treat Gram-positive bacterial infections in the clinic. The aim of this study was to provide a therapeutic reference for the clinical application and dosage regimen adjustment of teicoplanin by identifying factors associated with its plasma trough concentration (Ctrough). A retrospective study was performed on patients with suspected or documented Gram-positive infections who were hospitalized from November 2017 to January 2020 and treated with teicoplanin while undergoing routine therapeutic drug monitoring (TDM). A total of 112 Ctrough trough measurements were obtained from 72 patients were included in this study. SPSS software was used for correlation analysis and receiver operator characteristic curve (ROC) analysis. The Ctrough for teicoplanin showed statistically significant relationships (P<0.05) with PLT, Scr, CLcr, eGFR, BUN and Cys-C. ROC curve analysis revealed that CLcr and eGFR were more sensitive and specific for Ctrough compared to the other factors. These findings should be considered in the clinical application of teicoplanin and for its dosage adjustment.

Characteristics of Gram-positive cocci infection and the therapeutic effect after liver transplantation / 中南大学学报(医学版)

OBJECTIVES@#Gram-positive cocci is the main pathogen responsible for early infection after liver transplantation (LT), posing a huge threat to the prognosis of liver transplant recipients. This study aims to analyze the distribution and drug resistance of Gram-positive cocci, the risk factors for infections and efficacy of antibiotics within 2 months after LT, and to guide the prevention and treatment of these infections.@*METHODS@#In this study, data of pathogenic bacteria distribution, drug resistance and therapeutic efficacy were collected from 39 Gram-positive cocci infections among 256 patients who received liver transplantation from donation after citizens' death in the Third Xiangya Hospital of Central South University from January 2019 to July 2022, and risk factors for Gram-positive cocci infection were analyzed.@*RESULTS@#Enterococcus faecium was the dominant pathogenic bacteria (33/51, 64.7%), followed by Enterococcus faecalis (11/51, 21.6%). The most common sites of infection were abdominal cavity/biliary tract (13/256, 5.1%) and urinary tract (10/256, 3.9%). Fifty (98%) of the 51 Gram-positive cocci infections occurred within 1 month after LT. The most sensitive drugs to Gram-positive cocci were teicoplanin, tigecycline, linezolid and vancomycin. Vancomycin was not used in all patients, considering its nephrotoxicity. Vancomycin was not administered to all patients in view of its nephrotoxicity.There was no significant difference between the efficacy of daptomycin and teicoplanin in the prevention of cocci infection (P>0.05). Univariate analysis indicated that preoperative Model for End-Stage Liver Disease (MELD) score >25 (P=0.005), intraoperative red blood cell infusion ≥12 U (P=0.013) and exposure to more than 2 intravenous antibiotics post-LT (P=0.003) were related to Gram-positive cocci infections. Multivariate logistic regression analysis revealed that preoperative MELD score >25 (OR=2.378, 95% CI 1.124 to 5.032, P=0.024) and intraoperative red blood cell transfusion ≥ 12 U (OR=2.757, 95% CI 1.227 to 6.195, P=0.014) were independent risk factors for Gram-positive cocci infections after LT. Postoperative Gram-positive cocci infections were reduced in LT recipients exposing to more than two intravenous antibiotics post-LT (OR=0.269, 95% CI 0.121 to 0.598, P=0.001).@*CONCLUSIONS@#Gram-positive cocci infections occurring early after liver transplantation were dominated by Enterococcus faecalis infections at the abdominal/biliary tract and urinary tract. Teicoplanin, tigecycline and linezolid were anti-cocci sensitive drugs. Daptomycin and teicoplanin were equally effective in preventing cocci infections due to Gram-positive cocci. Patients with high preoperative MELD score and massive intraoperative red blood cell transfusion were more likely to suffer Gram-positive cocci infection after surgery. Postoperative Gram-positive cocci infections were reduced in recipients exposing to more than two intravenous antibiotics post-LT.

Adverse drug reaction monitoring during antimicrobial therapy for septicemia patients at a university hospital in New Delhi

BACKGROUND/AIMS: Adverse drug reaction (ADR) is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product. The present study was conducted in order to monitor the frequency and severity of ADR during antimicrobial therapy of septicemia. METHODS: A prospective, observational, and noncomparative study was conducted over a period of 6 months on patients of septicemia admitted at a university hospital. Naranjo algorithm scale was used for causality assessment. Severity assessment was done by Hartwig severity scale. RESULTS: ADRs in selected hospitalized patients of septicemia was found to be in 26.5% of the study population. During the study period, 12 ADRs were confirmed occurring in 9, out of 34 admitted patients. Pediatric patients experienced maximum ADRs, 44.4%. Females experienced a significantly higher incidence of ADRs, 66.7%. According to Naranjo’s probability scale, 8.3% of ADRs were found to be definite, 58.3% as probable, and 33.3% as possible. A higher proportion of these ADRs, 66.7% were preventable in nature. Severity assessment showed that more than half of ADRs were moderate. Teicoplanin was found to be the commonest antimicrobial agent associated with ADRs, followed by gemifloxacin and ofloxacin. CONCLUSIONS: The incidence and severity of ADRs observed in the present study was substantially high indicating the need of extra vigilant during the antimicrobial therapy of septicemia.

Antibioticoterapia y nuevas terapias no farmacológicas en infecciones por clostridium diffici / Antibiotic therapy and new non-pharmacological therapies in clostridium diffici infections

Resumen:La infección por Clostridium difficile es la principal causa de diarrea infecciosa en pacientes hospitalizados. Los pacientes pueden ser portadores asintomáticos o presentar desde una diarrea leve a una colitis pseudomembranosa, megacolon tóxico, sepsis y muerte. El manejo de esta infección sigue presentando puntos de controversia, tanto en la elección del mejor método diagnóstico como en el tratamiento. En los casos en los cuales la infección por este agente fue confirmada la primera y más efectiva medida es suspender la antibioticoterapia que el paciente este recibiendo, en la medida de lo posible. El tratamiento se basa en tres agentes clásicos: metronidazol, vancomicina y teicoplanina con la más reciente adición de fidaxomicina y ridinilazol. Pacientes con presentación severa muchas veces requieren resolución quirúrgica además de las medidas de soporte y monitoreo. El objetivo de esta revisión es ofrecer información actualizada sobre la patogénesis y estrategias terapéuticas sobre el manejo de la infección por este patógeno.

Abstract:Clostridium difficile infection is the leading cause of hospital acquired diarrhea. The patients can be asymptomatic carriers or present a mild diarrhea, a pseudomembranous colitis, toxic megacolon, sepsis and death. There is controversy in this infection's including the best method of diagnosis and also regarding therapeutic regimen.In cases in which Clostridium infection is confirmed, the first and most effective measure is the withdrawal of any antibiotic treatment the patient is receiving, if possible. The antimicrobial treatment is based on three classic agents: metronidazole, vancomycin and teicoplanin, along with the recent addition of fidaxomicin and ridinilazol.Patients presenting serious symptoms, in addition to appropriate support and monitoring measures, may require surgical treatment. This review's aim is to provide an update on the pathogenesis, and therapeutic strategies on the management of this pathogen.

Correlation between Infective Factors and Antibiotic Resistance in Enterococci Clinical Isolates in West of Iran / 전남의대학술지

The present study was done to scrutinize the possible relation between infective genes and antimicrobial resistance in Enterococcus faecalis and Enterococcus faecium. Considering the fact that the presence of recognized infective determinants among clinical isolates may promote the emergence of infections and persistence of Enterococci in hospital settings, which can lead to an increase in antimicrobial resistance. 175 E. faecalis and 67 E. faecium isolated from clinical specimens were used. The isolates were identified, and then antibiotic susceptibility testing was performed. The MIC of vancomycin and teicoplanin were determined by broth microdilution method. The presence of infective genes esp, hyl and asa₁ was scrutinized using PCR. Of the 280 enterococcal isolates, 175 (62.5%) isolates were identified as E. faecalis, 67 (24%) as E. faecium and 38 (13.5%) as Enterococcus spp. The results of the antibiotic susceptibility testing showed resistance rates of 5% and 73% to vancomycin and teicoplanin in E. faecalis and E. faecium isolates, respectively. The statistical analysis showed that the esp infective gene has significant associations with ciprofloxacin, erythromycin and tetracycline in E. faecium and with chloramphenicol in E. faecalis strains; the hyl with teicoplanin and vancomycin in E. faecium strains; and also asa₁ with vancomycin in E. faecium and with ampicillin and chloramphenicol in E. faecalis strains. Regarding the relationships between virulence genes and antibiotic resistance in strains of E. faecalis and E. faecium, detection of infective factors associated with invasive diseases has become a major issue of concern.

Response of Vancomycin according to Steroid Dosage in Pediatric Patients with Culture-Proven Bacterial Meningitis / 감염과화학요법

BACKGROUND: This study aimed to evaluate the efficacy of combined vancomycin and steroid therapy for the treatment of culture-proven bacterial meningitis in pediatric patients. MATERIALS AND METHODS: We identified a total of 86 pediatric patients with culture-positive cerebrospinal fluid who were treated at our facility between 2005 and 2015. Ten of these patients (5 boys and 5 girls) received first-line treatment with vancomycin as the initial form of therapy. All cultured bacteria were sensitive to vancomycin. We retrospectively analyzed these cases to examine the relationship between concomitant steroid dosage and antibiotic treatment effectiveness. RESULTS: Nine of the 10 patients included in our analysis received steroid treatment. Of these, 3 received high-dose steroid therapy and 6 received low-dose steroid therapy. Five patients did not respond to vancomycin, including all 3 patients in the high-dose steroid group and 2 patients in the low-dose steroid group. Our analysis confirmed that the response rate to vancomycin treatment was significantly reduced in accordance with steroid dosage (P = 0.035). Patients who did not to respond to vancomycin with concomitant high-dose steroid administration improved clinically after the substitution of vancomycin with teicoplanin. CONCLUSION: The use of steroids, especially in high doses, may impair the effectiveness of vancomycin for treating bacterial meningitis in pediatric patients. Physicians should be cautious when administering concomitant steroid therapy and should carefully monitor the steroid dosage.

Correlation between Infective Factors and Antibiotic Resistance in Enterococci Clinical Isolates in West of Iran / 전남의대학술지

The present study was done to scrutinize the possible relation between infective genes and antimicrobial resistance in Enterococcus faecalis and Enterococcus faecium. Considering the fact that the presence of recognized infective determinants among clinical isolates may promote the emergence of infections and persistence of Enterococci in hospital settings, which can lead to an increase in antimicrobial resistance. 175 E. faecalis and 67 E. faecium isolated from clinical specimens were used. The isolates were identified, and then antibiotic susceptibility testing was performed. The MIC of vancomycin and teicoplanin were determined by broth microdilution method. The presence of infective genes esp, hyl and asa₁ was scrutinized using PCR. Of the 280 enterococcal isolates, 175 (62.5%) isolates were identified as E. faecalis, 67 (24%) as E. faecium and 38 (13.5%) as Enterococcus spp. The results of the antibiotic susceptibility testing showed resistance rates of 5% and 73% to vancomycin and teicoplanin in E. faecalis and E. faecium isolates, respectively. The statistical analysis showed that the esp infective gene has significant associations with ciprofloxacin, erythromycin and tetracycline in E. faecium and with chloramphenicol in E. faecalis strains; the hyl with teicoplanin and vancomycin in E. faecium strains; and also asa₁ with vancomycin in E. faecium and with ampicillin and chloramphenicol in E. faecalis strains. Regarding the relationships between virulence genes and antibiotic resistance in strains of E. faecalis and E. faecium, detection of infective factors associated with invasive diseases has become a major issue of concern.

Comparison of Multilocus Sequence Typing Change Patterns of Vancomycin-Resistant Enterococcus faecium from 2015 to 2017 / 대한임상미생물학회지

BACKGROUND: Multilocus sequence typing (MLST) is useful in determining the long-term evolutionary process and minimizes differences in experimental results across individuals and laboratories. It is also useful in determining evolutionary origins and backgrounds of bacterial species. This study carries out MLST analysis on VanA-type vancomycin-resistant Enterococcus faecium isolated from patient specimens in a single university hospital over nine years in order to observe changes in genetic evolution over time. METHODS: During the years from 2007 to 2015, 44 clinical isolates of vanA-containing E. faecium were collected from Ajou University Hospital in Korea. Species were identified by the VitekII system (bio-Merieux, USA), and antibiotic susceptibility testing was performed by disk diffusion and E-test according to Clinical and Laboratory Standards Institute (CLSI) guidelines. To determine genetic relatedness, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF M/S) was employed. To characterize clonal diversity, MLST analysis was used. RESULTS: All isolates were highly resistant to ampicillin, ciprofloxacin, and vancomycin but showed variable levels of resistance to teicoplanin. The 44 clinical isolates were genetically unrelated according to MALDI-TOF M/S analysis. MLST showed that the clinical isolates harbored 6 sequence types (ST), with ST17 (n=19) being the most common, followed by ST78 (n=13), ST192 (n=6), ST64 (n=4), ST262 (n=1), and ST414 (n=1). CONCLUSION: The MLST analysis showed that the sequence types of most isolates belonged to clonal complex 17 This is consistent with outbreaks in hospitals. We had single observations for ST262 and ST414, suggesting that they were random occurrences. MLST can be useful for speculating the genetic evolution of VanA-containing E. faecium isolates.

[Molecular evaluation of vanA and vanB genes of enterococci isolates resistant to Vancomycin and Teicoplanin]

Background and Objective: Enterococci is gram positive bacteria which is the inhabitants of gastrointestinal tract. Hospital infections and antibiotic resistance to enterococci is increased. This study was done to determine the molecular evaluation of vanA and vanB genes of enterococci isolates resistant to Vancomycin and Teicoplanin

Methods: In this descriptive study, 113 isolates samples were collected and identified according to biochemical test and cultural characteristics in Ali ibn Abi Talib hospital in Zahedan, Iran. Antibiogram test was done to determine antibiotic resistance pattern. E-test strip was used to evaluate the minimum inhibitory of concentration [MIC]. PCR was used to detect the vanA and vanB genotype in Vancomycin and Teicoplanin resistance enterococci

Results: 92%, 6.2% and 1.8% of isolated samles collocted from urine, blood culture and pleura fluid, respectively. According to phenotype, 18.6% and 17.69% were resistance to Vancomycin and Teicoplanin, respectively. Resistance was observed in strains of Enterococcus faecalis and Enterococcus faecium. VanA genotype was seen in all of the resistance isolated species

Conclusion: This study showed that strains of Enterococcus faecalis and Enterococcus faecium have more antibiotic resistance to the Vancomycin and Teicoplanin, morever vanA genotype precence in all of resistance isolated samples

Antimicrobial susceptibility of Brazilian Clostridium difficile strains determined by agar dilution and disk diffusion

Abstract Clostridium difficile is a leading cause of diarrhea in hospitalized patients worldwide. While metronidazole and vancomycin are the most prescribed antibiotics for the treatment of this infection, teicoplanin, tigecycline and nitazoxanide are alternatives drugs. Knowledge on the antibiotic susceptibility profiles is a basic step to differentiate recurrence from treatment failure due to antimicrobial resistance. Because C. difficile antimicrobial susceptibility is largely unknown in Brazil, we aimed to determine the profile of C. difficile strains cultivated from stool samples of inpatients with diarrhea and a positive toxin A/B test using both agar dilution and disk diffusion methods. All 50 strains tested were sensitive to metronidazole according to CLSI and EUCAST breakpoints with an MIC90 value of 2 μg/mL. Nitazoxanide and tigecycline were highly active in vitro against these strains with an MIC90 value of 0.125 μg/mL for both antimicrobials. The MIC90 were 4 μg/mL and 2 μg/mL for vancomycin and teicoplanin, respectively. A resistance rate of 8% was observed for moxifloxacin. Disk diffusion can be used as an alternative to screen for moxifloxacin resistance, nitazoxanide, tigecycline and metronidazole susceptibility, but it cannot be used for testing glycopeptides. Our results suggest that C. difficile strains from São Paulo city, Brazil, are susceptible to metronidazole and have low MIC90 values for most of the current therapeutic options available in Brazil.

Prevalence and Clinical Impact of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolated From Hospitalized Patients

BACKGROUND: We estimated the prevalence and clinical impact of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA). The concordance between macromethod and glycopeptide resistance detection (GRD) E tests was determined. In addition, predictors of clinical outcomes in hospitalized patients with S. aureus bacteremia (SAB) or pneumonia (SAP) were evaluated. METHODS: We obtained 229 consecutive S. aureus isolates from all hospitalized patients at two university hospitals located in Busan and Yangsan, Korea. Standard, macromethod, and GRD E tests were performed. Additionally, we reviewed the medical records of all patients. Among the 229 patients, predictors of clinical outcomes were analyzed for 107 patients with SAB and 39 with SAP. RESULTS: Among the 229 isolates, 34.5% of S. aureus isolates and 50.7% of methicillin-resistant S. aureus isolates exhibited the hVISA phenotype based on the macromethod E test. hVISA was nearly associated with treatment failure in patients with SAB (P=0.054) and was significantly associated with treatment failure in patients with SAP (P=0.014). However, hVISA was not associated with 30-day mortality in patients with SAB or SAP. The concordance between the macromethod and GRD E tests was 84.2%. CONCLUSIONS: hVISA is quite common in the southeastern part of Korea. hVISA is associated with treatment failure in patients with SAP.

Are the leading drugs against Staphylococcus aureus really toxic to cartilage?

Many studies have shown that the toxic effects of local antibiotics on bone and cartilage limit orthopedic surgeons. In this study, we evaluated three antibacterial agents used locally to treat highly mortal and morbid diseases in the field of orthopedics, such as septic arthritis. Are vancomycin, teicoplanin, and line-zolid, which are archenemies of Staphylococcus aureus, really toxic to chondrocytes? The purpose of the study was to investigate the effects of antibiotics, which are used against S. aureus, on human chondrocytes in vitro

Primary cell cultures obtained from gonarthrosis patients were divided into two main groups. One of these groups was designated as the control chondrocyte culture. The other group was divided into three subgroups, and each group was exposed to vancomycin, teicoplanin, or linezolid. Cell culture samples were characterized by immunophenotyping following incubation with the three different antibiotics. Before and after the agents were administered, the cultures were subjected to inverted and environmental scanning electron microscopy. The number of live cells and the proliferation rate were monitored with the MTT-assay. We found that vancomycin, teicoplanin, and linezolid do not have chondrotoxic effects

Vancomycin, teicoplanin, and linezolid had no chondrotoxic activity during in vitro culture, which supports the argument that these agents can safely be used in orthopedic surgery, especially against methicillin-resistant S. aureus agents

Molecular Epidemiology of Staphylococcus aureus among Patients with Skin and Soft Tissue Infections in Two Chinese Hospitals / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Staphylococcus aureus is one of the predominant causes of skin and soft tissue infections (SSTIs), but limited data were available regarding the characterization of S. aureus from SSTIs patients in Jiangsu Province in China. We aimed to investigate the molecular epidemiology of S. aureus among SSTIs patients in two hospitals of Jiangsu Province.</p><p><b>METHODS</b>Sixty-two patients with SSTIs from two Chinese hospitals in Jiangsu Province were enrolled in this study, and 62 S. aureus isolates were collected from February 2014 to January 2015. S. aureus isolates were characterized by antimicrobial susceptibility testing, toxin gene detection, and molecular typing with sequence type, Staphylococcus protein A gene type, accessory gene regulator (agr) group, and Staphylococcal cassette chromosome mec t ype.</p><p><b>RESULTS</b>Sixteen (25.8%) methicillin-resistant S. aureus (MRSA) isolates were detected, and there was no isolate found resistant to vancomycin, teicoplanin, sulfamethoxazole-trimethoprim, and linezolid. The sei was the toxin gene most frequently found, and no lukS/F-PV-positive isolates were detected among the SSTIs' patients. Molecular analysis revealed that ST398 (10/62, 16.1%; 2 MRSA and 8 methicillin-susceptible S. aureus) to be the dominant clone, followed by ST5 (8/62, 12.9%) and ST7 (8/62, 12.9%).</p><p><b>CONCLUSIONS</b>The livestock ST398 was the most common clone among patients with S. aureus SSTIs in Jiangsu Province, China. Surveillance and further studies on the important livestock ST398 clone in human infections are necessarily requested.</p>

Glycopeptide Antibiotics: Structure and Mechanisms of Action

Glycopeptides of the clinically important antibiotic drugs are glycosylated cyclic or polycyclic nonribosomal peptides. Glycopeptides such as vancomycin and teicoplanin are often used for the treatment of gram-positive bacteria in patients. The increased incidence of drug resistance and inadequacy of these therapeutics against gram-positive bacterial infections would be the formation and clinical development of more variable second generation of glycopeptide antibiotics: semisynthetic lipoglycopeptide analogs such as telavancin, dalbavancin, and oritavancin with improved activity and better pharmacokinetic properties. In this review, we describe the development of and bacterial resistance to vancomycin, teicoplanin, and semisynthetic glycopeptides (teicoplanin, dalbavancin, and oritavancin). The clinical influence of resistance to glycopeptides, particularly vancomycin, are also discussed.

The first report of the vanC1 gene in Enterococcus faecium isolated from a human clinical specimen

The vanC1 gene, which is chromosomally located, confers resistance to vancomycin and serves as a species marker for Enterococcus gallinarum. Enterococcus faecium TJ4031 was isolated from a blood culture and harbours the vanC1gene. Polymerase chain reaction (PCR) assays were performed to detect vanXYc and vanTc genes. Only the vanXYc gene was found in the E. faecium TJ4031 isolate. The minimum inhibitory concentrations of vancomycin and teicoplanin were 2 µg/mL and 1 µg/mL, respectively. Real-time reverse transcription-PCR results revealed that the vanC1and vanXYc genes were not expressed. Pulsed-field gel electrophoresis and southern hybridisation results showed that the vanC1 gene was encoded in the chromosome. E. faecalis isolated from animals has been reported to harbour vanC1gene. However, this study is the first to report the presence of the vanC1gene in E. faecium of human origin. Additionally, our research showed the vanC1gene cannot serve as a species-specific gene of E. gallinarum and that it is able to be transferred between bacteria. Although the resistance marker is not expressed in the strain, our results showed that E. faecium could acquire the vanC1gene from different species.

Changing Patterns of Bacterial Strains in Adults and Children With Otitis Media in Korean Tertiary Care Centers

OBJECTIVES: Otitis media (OM) is an infectious disease that affects all age brackets. Aural discharge is a typical symptom, occurring in all subtypes of OM. We have compared the identity and antibiotic sensitivity of bacteria isolated from aural discharges of adults and children with various types of OM, including acute OM (AOM), OM with effusion (OME), chronic OM (COM), and cholesteatomatous OM (CSOM). METHODS: The study involved 2,833 patients who visited five tertiary hospitals between January 2001 and December 2010 and were diagnosed with AOM, OME, COM, or CSOM. The patients were divided into a pediatric group and an adult group, and the distribution of cultured bacteria and their antibiotic sensitivity were compared in the two groups. RESULTS: Bacterial detection rates were higher in adults than in children with OME and COM (P=0.000 each). The majority of the bacteria cultured from patients with AOM and OME bacteria were methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus pneumoniae. Bacteria cultured from children were more susceptible to antibiotics (P=0.002) and had higher antibiotic sensitivity (P=0.001) than were bacteria cultured from adults. The majority of bacteria culture from patients with COM and CSOM were MSSA and pathogenic Pseudomonas aeruginosa. The frequency of methicillin-resistant Staphylococcus aureus was significantly higher in adults than in children, and more strains of bacteria isolated from adults were sensitive to the antibiotics septrin, vancomycin, and teicoplanin. CONCLUSION: Bacteria cultured from children were more susceptible to antibiotics and had higher antibiotic sensitivity than did bacteria cultured from adults.

Therapeutic Drug Concentrations of Teicoplanin in Clinical Settings / 감염과화학요법

BACKGROUND: Teicoplanin is a glycopeptide antibiotic that is widely used in clinical practice for the treatment of infections caused by drug-resistant Gram-positive bacteria. The aim of this study was to analyze plasma teicoplanin concentrations to determine the percentage of patients in whom therapeutic concentrations of teicoplanin were achieved in clinical practice. MATERIALS AND METHODS: The plasma teicoplanin concentrations of hospitalized patients receiving treatment at a teaching hospital were retrospectively analyzed. The target level was defined as a plasma teicoplanin concentration of 10 mg/L or greater, since this was generally regarded as the lower limit of the optimal concentration range required for the effective treatment of a majority of infections. RESULTS: Patients with sub-optimal (< 10 mg/L) plasma teicoplanin concentrations constituted nearly half of the total study population. The majority of these patients received the recommended loading dose, which were three 400 mg doses administered every 12 hours. Sub-group analysis showed a trend that the group receiving loading dose was more likely to reach the optimal teicoplanin concentration. CONCLUSIONS: The data revealed that a significant proportion of patients in clinical practice achieved only sub-optimal teicoplanin concentrations, which emphasizes the importance of the mandatory use of loading dose and routine therapeutic drug monitoring. Treatment reassessment and simulation of individual dose regimens may also be necessary to achieve optimal drug concentrations.

Is Therapeutic Drug Monitoring of Teicoplanin Useful? / 감염과화학요법

No abstract available.

Adverse Drug Reactions of Long-term Intravenous Antibiotics in Patients with Pyogenic Spondylitis

OBJECTIVE: The purpose of this study was to investigate the incidence, cause, and influence of the adverse drug reactions (ADRs) associated with long-term intravenous antibiotics in patients with pyogenic spondylitis (PS). METHODS: We retrospectively reviewed the medical records of 84 patients with PS who underwent intravenous antibiotic therapy in our hospital from January 2001 to December 2012. ADRs were categorized to drug eruption, acute renal failure (ARF), hematologic toxicity, toxic hepatitis, pseudomembranous colitis (PMC), drug fever, and neuronal toxicity. Incidence and onset time of each ADR after antibiotic therapy were analyzed with the incidence of ADRs according to types of antibiotics. RESULTS: ADRs occurred in 38 of the 84 patients (incidence: 45.2%). The use of antibiotics was longer in the patients with ADRs (62.7 days) than in the patients without ADRs (44.3 day). The incidence of drug eruption, ARF, hematologic toxicity, toxic hepatitis, PMC, drug fever, and neuronal toxicity were 22.6, 11.9, 11.9, 10.7, 7.1, 3.6%, and 1.2%, respectively. The duration of antibiotics administration was related to the occurrence of PMC (p=0.001). ADRs were more common in patients treated by glycopeptides including vacomycin and teicoplanin. CONCLUSION: The incidence of ADRs due to long-term intravenous antibiotics was as high as 45.2% in patients with PS. Therefore, we speculate that the possibility of delayed ADRs should be considered after long-term use of the antibiotics. Furthermore, close observation is mandatory to identify and treat ADRs promptly, even though PS revealed the improvement after antibiotic therapy.

Interpretation of Epithelial Lining Fluid Concentrations of Antibiotics against Methicillin Resistant Staphylococcus aureus / 감염과화학요법

Although antibiotics whose epithelial lining fluid (ELF) concentrations are reported high tend to be preferred in treatment of pneumonia, measurement of ELF concentrations of antibiotics could be misled by contamination from lysis of ELF cells and technical errors of bronchoalveolar lavage (BAL). In this review, ELF concentrations of anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics were interpreted considering above confounding factors. An equation used to explain antibiotic diffusion into CSF (cerebrospinal fluid) was adopted: ELF/free serum concentration ratio = 0.96 + 0.091 x ln (partition coefficient / molecular weight1/2). Seven anti-MRSA antibiotics with reported ELF concentrations were fitted to this equation to see if their ELF concentrations were explainable by the penetration capacity only. Then, outliers were modeled under the assumption of varying contamination from lysed ELF cells (test range 0-10% of ELF volume). ELF concentrations of oritavancin, telavancin, tigecycline, and vancomycin were well described by the diffusion equation, with or without additional impact from cell lysis. For modestly high ELF/free serum concentration ratio of linezolid, technical errors of BAL should be excluded. Although teicoplanin and iclaprim showed high ELF/free serum ratios also, their protein binding levels need to be cleared for proper interpretation. At the moment, it appears very premature to use ELF concentrations of anti-MRSA antibiotics as a relevant guide for treatment of lung infections by MRSA.