Society Of Chemotherapy Research Articles

Non-inferior comparative study comparing one or two day antimicrobial prophylaxis after clean orthopaedic surgery (NOCOTA study): a study protocol for a cluster pseudo-randomized controlled trial comparing duration of antibiotic prophylaxis

BackgroundAntimicrobial prophylaxis (AMP) is one of the most important measures for preventing surgical site infections (SSIs); however, controversies remain regarding its adequate duration. Although the World Health Organization and the Center for Disease Control and Prevention do not recommend additional AMP after closure, the American Society of Health-System Pharmacists and the Musculoskeletal Infection Society permit the use of postoperative AMP, but recommend discontinuation within 24 h. Similarly, the Japanese Society of Chemotherapy and the Japan Society for Surgical Infection also permit AMP within 24–48 h after various orthopaedic procedures. In these guidelines, recommendations regarding AMP duration were weak due to a relative lack of evidence, and currently, there is no high-quality evidence comparing AMP use within 24 h versus 24–48 h regarding orthopaedic procedures. Urinary tract infection (UTI) and respiratory tract infection (RTI) are also important health care-associated infections (HAIs) faced after surgery. Although AMP duration may affect these HAIs, its effects have not been well evaluated.MethodsWe have organized a multicenter, prospective, cluster pseudo-randomized controlled trial to examine the non-inferiority of shorter AMP duration (within 24 h) against longer duration (24–48 h) in preventing postoperative HAIs. Participating facilities will be divided into two groups. In Group 24, AMP will be discontinued within 24 h after surgery. In Group 48, AMP will be discontinued within 24–48 h after surgery. The group allocation will be switched every 2 months until the targeted recruitment (500 participants per group) is met.The primary outcome will be the cumulative incidence of all HAIs (SSI, UTI, RTI, and other infectious diseases), which require antibiotic therapies within 30 days after surgery. In addition to mortality and cardiovascular events, prolonged hospitalization (> 30 days) and the rate of antibiotic resistance rate of SSI pathogens will also be evaluated. Outcomes will be evaluated within 30–180 days after surgery in person by the surgeon, by mail, or by telephone survey. Data will be analyzed by a statistician not engaged in data collection.DiscussionThis study may provide valuable information for developing future recommendations for adequate AMP duration after clean orthopaedic surgery.Trial registrationUMIN000030929, registered January 22, 2018.

Invasive candidiasis and candidemia in pediatric and neonatal patients: A review of current guidelines.

Several international and national guidelines have been proposed for the treatment and prevention of invasive candidiasis/candidemia (IC/C) in both neonatal and pediatric patients. This article is a review of the current guidelines, recommendations, and expert panel consensus of a number of associations and conferences on the prevention and management of IC and candidemia in both pediatric and neonatal patients. The investigated resources included the Infectious Diseases Society of America, the European Conference on Infection in Leukaemia, the European Society of Clinical Microbiology and Infectious Diseases, the German Speaking Mycological Society/Paul-Ehrlich Society for Chemotherapy, as well as the Canadian, Middle Eastern, and Australian guidelines. Echinocandins and liposomal amphotericin B (L-AmB) are the first-line agents in the treatment of IC and candidemia both for immunocompetent and immunocompromised pediatric patients. The recommendations suggested to keep patients under sterile conditions for at least 14 days after blood cultures as the prompt initiation of antifungal treatment. Guidelines addressing the neonates recommended to use L-AmB, deoxycholate AmB (D-AmB), and fluconazole based on three main principles of no previous exposure to azoles, the prompt initiation of antifungal treatment, and control of predisposing underlying conditions. Despite minor differences among the investigated guidelines, general treatment recommendations suggest the prompt initiation of antifungal treatment and control of all predisposing underlying conditions.

Comparison of twice a day and three times a day meropenem administration in elderly patients in a Japanese community hospital.

ABSTRACTMeropenem (MEPM) is a broad-spectrum antibiotic prescribed to patients with moderate or severe pneumonia. It is well recognized that appropriate medicine reduces the burden on not only young patients but elderly ones as well. We enrolled 56 patients aged 75 and over who were diagnosed with moderate or severe pneumonia (body temperature: ≧37.5 °C; white blood cell (WBC) count: ≧10,000/μL; C-reactive protein (CRP): ≧4 mg/dL) on the basis of Clinical Evaluation Methods for New Antimicrobial Agents to Treat Respiratory Infections defined by the Japanese Society of Chemotherapy, at the National Hospital Organization Kanazawa Medical Center from January 1, 2007 to May 31, 2010.Forty-two patients were given MEPM twice a day and 14 were given the same drug three times a day in a Japanese community hospital. After four days, the three times a day group showed significant decreases in body temperature, WBC count, and CRP level, which are commonly used indices for evaluating therapeutic effects. Similarly, the twice a day group showed decreases of those indices, and both treatments had no serious adverse effects. Simulation analysis based on the pharmacokinetics-pharmacodynamics (PK/PD) theory revealed that both treatments effectively inhibited the activities of Pneumococcus, Haemophilus influenzae, Providencia stuartii, and Staphylococcus aureus, which are the major bacteria in the patients. In this retrospective study, simulation analysis based on the PK/PD theory revealed that even the twice a day MEPM administration has sufficient effectiveness against pneumonia. It also may pave the way for the use of personalized medicine in the patients.

Ceftazidime/Avibactam: Who Says You Can't Teach an Old Drug New Tricks?

Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 - September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa. Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. By adding avibactam to ceftazidime, clinicians' antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases: The Japanese Association for Infectious Diseases/Japanese Society of Chemotherapy - The JAID/JSC Guide to Clinical Management of Infectious Disease/Guideline-preparing Committee Respiratory Infectious Disease WG.

The Japanese Association for Infectious Diseases (JAID) and Japanese Society of Chemotherapy (JSC) announced the “Guide for the Use of Antimicrobial Drugs” in 2001 and the “Guidelines for the Use of Antimicrobial Drugs” in 2005. Subsequently, the “The JAID/JSC guide to clinical management of infectious diseases 2011” was published. With its revision, guidelines were newly prepared.

Invasive candidiasis and candidaemia in neonates and children: update on current guidelines.

Invasive candidiasis (IC) and candidaemia are leading causes of infectious morbidity and mortality among immunocompromised paediatric patients and those admitted to intensive care units. Despite improvements in diagnosis, prevention and treatment, both mortality rates and the economic burden of disease still remain high. To address this issue, several international societies and organisations have proposed guidelines for the management of IC/candidaemia in both neonates and children. In this article, we review current recommendations of the Infectious Diseases Society of America, the European Conference on Infection in Leukaemia, the European Society of Clinical Microbiology and Infectious Diseases and the German Speaking Mycological Society/Paul-Ehrlich Society for Chemotherapy for the management and prevention of IC/candidaemia in children and neonates.

Diagnosis and management of Skin and Soft-Tissue Infections (SSTI): a Literature Review and Consensus Statement on Behalf of the Italian Society of Infectious Diseases and International Society of Chemotherapy

Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges and resulting in significant morbidity and mortality among patients as well as increased healthcare costs. Eight members of the SSTI working group of the Italian Society of infectious Diseases prepared a draft of the statements, grading the quality of each piece of evidence after a careful review of the current literature using MEDLINE database and their own clinical experience. Statements were graded for their strength and quality using a system based on the one adopted by the infectious Diseases Society of America (IDSA). The manuscript was successively reviewed by seven members of the SSTI working group of the international Society of Chemotherapy, and ultimately re-formulated by all experts. The microbiological and clinical aspects together with diagnostic features were considered for uncomplicated and complicated SSTIs. Antimicrobial therapy was considered as well —both empirical and targeted to methicillin-resistant Staphylococcus aureus (MRSA) and/or other main pathogens.

A report from the committee on microbroth dilution antimicrobial susceptibility testing

In 1968, the Japanese Society of Chemotherapy (JSC) established an agar dilution method for MIC determinations of aerobic bacteria [1]. In 1979, the JSC established an agar dilution method for MIC determinations of anaerobic bacteria. Furthermore, a revision of the agar dilution standard was made in 1980, and this served as the standard method for MIC determinations for an extensive period of time in Japan. In 1990, the committee established a standard microbroth dilution method for MIC determinations. This method was modified in 1992 for fastidious aerobic and anaerobic bacteria [2]. In the development of standards for antimicrobial susceptibility testing, there has been a movement to incorporate pharmacologic as well as clinical considerations with respect to in vitro antimicrobial susceptibility interpretations. This trend reflects the need to respond to the emergence and spread of resistant microorganisms as well as a greater understanding of pharmacokinetics and pharmacodynamics and how it relates to improved patient outcome. The Clinical Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility (EUCAST) are among the professional organizations that proactively revise antimicrobial susceptibility testing on a regular basis. JSC has also been revising its standards. In 2007, the agar dilution method was revised. After the exclusion of selected organisms from the CLSI agar dilution standard, this method was adopted by the JSC [3]. With respect to revising the standard method for microbroth dilution antimicrobial susceptibility testing, a committee chaired by Keizo Yamaguchi was formed in January 2008. The subcommittee’s first task was to critically examine the methods for the antimicrobial susceptibility testing of Haemophilus influenzae. Although JSC and CLSI microbroth dilution methods both use a Mueller– Hinton base, the supplements differ. This difference had raised concerns among some Japanese clinical microbiology professionals that there were many issues with the CLSI method with respect to reported difficulties in measuring endpoints and the poor growth of some strains. Our first action was to send questionnaires to the members of the JSC and the Japanese Society for Clinical Microbiology to better understand the technical problems experienced in clinical microbiology laboratories regarding microbroth dilution testing of H. influenzae. From the responses to the questionnaire, it was clear that a major problem in routine testing was the poor growth of Members of the Microdilution Susceptibility Standards Committee: committee chairperson: Keizo Yamaguchi, committee members: Yoichi Hirakata, Intetsu Kobayashi, Masanari Ikedo, Akira Ohno.

Community Acquired Pneumonia

Community-acquired pneumonia (CAP) is a major cause of morbidity, of mortality, and of expenditure of medical resources. The etiology and antimicrobial susceptibility of CAP pathogens can differ by country. Treatment guidelines need to reflect the needs of individual countries based on pathogen susceptibility studies. Recent treatment guidelines for CAP in Korea were published by the Joint Committee of the Korean Academy of Tuberculosis and Respiratory Diseases, the Korean Society for Chemotherapy, and the Korean Society of Infectious Diseases. In this article, the etiologies, diagnoses, treatments for CAP will be reviewed and compared to the recent published Korean guidelines for CAP treatment.

The Charta of Milan: Basic Criteria for the Appropriate and Accurate Use of Antibiotics: Recommendations of the Italian Society of Chemotherapy

This article summarizes the recommendations drawn up by the Italian Society of Chemotherapy regarding the proper use of antimicrobial agents for infectious diseases.

Antibiotic resistance: the challenge from an industry perspective

Trained in medical microbiology and infectious diseases in the UK, Glenn Tillotson has over 20 years pharmaceutical experience in various areas, including clinical research, marketing, scientific communications, strategic development and global launch programs. Mainly in the field of anti-infectives, Tillotson has been instrumental in the development of ciprofloxacin and moxifloxacin, as well as other drugs in the Bayer portfolio. After leaving Bayer, he worked as a consultant microbiologist and, in 2003, consulted with Genesoft to help with the commercialization and launch of gemifloxacin, leading to the development of Oscient following the merger of Genesoft and Genome Therapeutics. From late 2003 to early 2006, he focused his efforts on the launch of gemifloxacin into US clinical practice, as well as comarketing and business development deals globally. In April 2006, Tillotson joined Replidyne Inc. as Executive Director of Scientific Affairs working on faropenem, REP 8839 and REP 3123. Presently, Tillotson is Head of Medical Affairs at ViroPharma Inc., where he oversees educational, publication and other related activities for Vancocin®, maribavir and Cinryze™. Most recently, Tillotson was a member of the Scientific Steering Committee for the International Society of Chemotherapy’s Symposium on Clostridium difficile in Leipzig, Germany. Here, he talks with Expert Review of Clinical Pharmacology about the challenge of antibiotic resistance from an industry perspective.

Update on Fungal Infections – introduction

An international update symposium on fungal infections took place in Madrid, Spain, from 29 February to 1 March 2008. Organized by the Spanish Society of Chemotherapy and supported by the International Society of Chemotherapy, Infections and Cancer (ISC) and the Federation of European Societies for Chemotherapy and Infections (FESCI), this conference covered the epidemiological, clinical, and therapeutic aspects of the most typical settings of fungal infections in adults: the non-neutropenic critically ill patient and the immunosuppressed patient (neutropenic or undergoing solid organ transplantation [SOT] or hematopoietic stem cell transplantation [HSCT]). The significance of fungal infection in these settings has increased greatly in recent years. This is due to better intrinsic knowledge of the diseases that predispose a patient to fungal infection and the hemodynamic and nutritional support that increase survival, and also to more effective prophylaxis and antimicrobial treatment. This greater knowledge of the disease and its complications allows the choice of specific therapeutic targets (antilymphocyte monoclonal antibodies, therapy with a prolonged neutropenic effect), or prophylactic schedules that predispose the patient not just to fungal infection, but also to the selection of fungal subspecies such as non-albicans Candida, Aspergillus terreus, Scedosporium species, Zygomycetes, etc. At the conference, the main antifungal agents were reviewed in order to consolidate prophylaxis and treatment schedules. The guidelines of the Infectious Disease Society of America (IDSA) [1] were taken as a reference for invasive candidiasis and aspergillosis [2], with specific considerations according to the model of infection and the patient’s profile. A change in the frequency and type of yeast isolates has emerged in intensive care units [3]. The current incidence of candidemia is around 1.5 episodes per 1000 days of intensive care unit (ICU) admission, with an attributable

Meeting report: Fourth Forum on Respiratory Tract Infections, Sitges, Spain, 8–11 February 2007

Over 420 delegates participated in this, the fourth of a biennial series of scientific meetings, drawing from 30 or more nations and encompassing the specialties of infectious diseases, clinical microbiology, pulmonary and general medicine and Industry inter alia. The 2007 Forum was chaired by Professors Antoni Torres Marti, Giuliana Gialdroni Grassi and Dr Peter Ball and received academic endorsement from the British Society for Antimicrobial Chemotherapy (BSAC), Italian Society for Chemotherapy, Spanish Pulmonology Society, Paul Ehrlich Society and the Société de Pneumologie de Langue Français. The Scientific Programme was scientifically and financially supported by the BSAC and a consortium of pharmaceutical companies. Discussion focused on key contemporary issues in respiratory tract infection (RTI), including the impact of antibiotic resistance on clinical outcomes and the continuing need for antibiotic conservation via evolving guidelines, the challenges of avian influenza, nosocomial RTIs and the emergence of new pathogens, e.g. community-acquired methicillin-resistant Staphylococcus aureus, novel antimicrobial agents, disease definitions (e.g. healthcare-associated pneumonia) and therapeutic assessment criteria, such as patient-reported outcome measures, in improving RTI management. The entire meeting was granted CME recognition (18 sessions) by the European Accreditation Council for continuing medical education.

P733 Thefirst nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy

P733 Thefirst nationwide surveillance of bacterial respiratory pathogens conducted by the Japanese Society of Chemotherapy

The MRSA patient in technical orthopaedics and rehabilitation. Part 2: Hygiene management

One of the multiresistant pathogens is methicillin-resistant Staphylococcus aureus (MRSA),which was increasingly found in the 1980's. In the USA, the ratio of MRSA rose from 2% in 1975 to 29% in 1991. A similarly steep rise was seen in Germany, with the Paul Ehrlich Society for Chemotherapy reporting a rise from 1.7% in 1990 to 15.7% in 1998. In order to control MRSA, the Clinic and Polyclinic of Technical Orthopaedics and Rehabilitation at the University Clinic Münster, Germany,has set up a comprehensive hygiene management programme for early detection and treatment of nosocomial infections. In addition to addressing the usual problems of MRSA carriers (e.g., higher mortality, longer hospital stays, stigmatisation), these preventive measures are also aimed at combating MRSA-caused cost increases.

Tom Bergan, 1939-2001

Tom Bergan, a rigorous scientist working in antimicrobial chemotherapy and a master in the field of pharmacokinetics and tissue penetration of antibiotics, a very capable President of the International Society of Chemotherapy, and one of our valued members of the Editorial Board of the Journal of Chemotherapy, died this summer after a long illness during which he remained dedicated to his work. Tom had been a true and loyal friend to the Journal of Chemotherapy, helping us to screen articles and participating in our editorial and congressional activities with his well known enthusiasm and expertise. Just this last April Tom came to Florence to participate in our Fourth Symposium on the Control of Surgical Infections. We will be publishing some of his comments from that meeting later this fall. In spite of his heavy work commitments Tom was always ready to devote himself to the fullest when asked to a scientific event, graciously taking on extra duties whenever asked. It is with real sorrow that we heard of his all too early demise: he will be truly missed. We offer our sincere condolences to his wife and family.

Urinary Bactericidal Activity and Pharmacokinetics of Enoxacin Versus Norfloxacin and Ciprofloxacin in Healthy Volunteers After a Single Oral Dose

In an open, randomised monocentric crossover study in six male and six female healthy volunteers, the urinary antibacterial activity and pharmacokinetics of enoxacin, norfloxacin and ciprofloxacin were assessed. Urine was collected up to 6 days, and venous blood samples up to 12 h, after a single oral dose of 400 mg enoxacin, 400 mg norfloxacin and 500 mg ciprofloxacin. Enoxacin (250 mg:l) demonstrated the highest peak concentration (median) in the urine (0‐6 h), followed by ciprofloxacin (237 mg:l) and norfloxacin (157 mg:l) as determined by the HPLC assay. The total amount (mean) excreted by the kidneys as parent drugs were as follows: enoxacin 54% of dose, ciprofloxacin 33% of dose, and norfloxacin 22% of dose. The mean plasma concentrations decreased from 1 to 4 h after administration for enoxacin from 1.9 to 1.4 mg:l, for ciprofloxacin from 2.0 to 0.8 mg:l and for norfloxacin from 1.3 to 0.5 mg:l. The antibacterial activity in urine was determined as urinary bactericidal titers (UBT), i.e. the highest 2-fold dilution of urine still bactericidal for the reference organism (E. coli ATCC 25922) and for five uropathogens with minimal inhibitory (MIC) and bactericidal (MBC) concentrations ranging from highly susceptible to resistant cultured from the urine of patients with complicated urinary tract infections (UTI). For the E. coli ATCC 25922, the organism with the lowest MIC, median UBTs of ciprofloxacin were present for 4 days, decreasing from 1:512 to 1:2, that of enoxacin for 2 days, decreasing from 1:256 to 1:4, and that of norfloxacin for 2 days, decreasing from 1:128 to 1:2. For the five uropathogens (with increasing MICs: K. pneumoniae, P. mirabilis, E. coli (resistant to nalidixic acid), P. aeruginosa and E. faecalis), the UBTs decreased in general, according to MICs, demonstrating the same relations of UBTs for ciprofloxacin (highest) versus enoxacin (medium) versus norfloxacin (lowest) with one exception (P. mirabilis) for which norfloxacin showed higher UBTs than enoxacin. The minimal urinary bactericidal concentrations (MUBC), as derived from urinary concentrations, and UBTs showed a fairly wide inter- and intraindividual range and were generally higher than the corresponding MBCs as determined in Mueller Hinton broth. In conclusion, according to antibacterial activity in urine determined as UBTs, a single oral dose of ciprofloxacin (500 mg) generally resulted in the highest and longest-lasting UBTs followed by that of enoxacin (400 mg) and norfloxacin (400 mg). A dose of 400 mg enoxacin can be expected to be at least equivalent if not superior to that of 400 mg norfloxacin. Only enoxacin and ciprofloxacin exhibited urinary bactericidal activity against all test organisms up to 12 h in all individuals. Therefore, clinical comparison of enoxacin versus ciprofloxacin in the treatment of complicated UTI could be worth testing. © 1998 Elsevier Science B.V.:International Society of Chemotherapy. All rights reserved.

Urinary Tract Infection in Pregnancy

Urinary tract infection is one of the most frequently seen ‘medical’ complications in pregnancy. The pioneering work of Edward Kass discovered that 6% of pregnant women had asymptomatic bacteriuria associated with increased prematurity and perinatal mortality compared to women with sterile urine. Screening for bacteriuria in pregnancy has become routine. The prevalence of asymptomatic bacteriuria as well as the associated complications described by Kass in 1962 are higher compared to most data collected in the 1980s and late 1990s in different populations in various parts of the world. Other factors such as vaginal colonization have been recognized as important contributors to preterm labour. The value of screening for bacteriuria has to be re-addressed considering methods, significance and costs. Treatment of urinary tract infection in pregnancy is critically reviewed. © 2001 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.

Clinical Breakpoints for Antimicrobial Agents in Pulmonary Infections and Sepsis: Report of The Committee for Japanese Standards for Antimicrobial Susceptibility Testing for Bacteria

The Commi t t ee for Japanese Standards for Antimicrobial Susceptibility Testing for Bacteria, Japan Society of Chemotherapy~ (chairman: Sachiko Goto, MD, Table 1) established the standard method of the Japan Society of Chemotherapy for microdilution antimicrobial susceptibility testing of bacteria that grow aerobically. 1 Fur thermore , the Commit tee (chairman: Atsushi Saito, MD) determined the standard method for microdilution antimicrobial susceptibility testing methods for bacteria that grow anaerobically and for bacteria that require special nutrients. 2 At the 41 st All Japan meet ing for the Japan Society of C h e m o t h e r a p y (Tokyo, 1993), the Commit tee proposed clinical breakpoints for antimicrobial agents which could be used in pu lmonary infections and sepsis, soliciting opinions from the m ember s of the Society.The originally proposed breakpoints were partially revised and here we submit the breakpoints in pu lmonary infections and sepsis as authorized by the Japan Society of Chemotherapy. I t would be ideal if breakpoints for ant imicrobial agents in any organ could be determined with the measu rement of M I C (minimum inhibitory concentrat ion), a quantitative designation of drug susceptibility. The breakpoints should be decided for each organ since concentration of antibiotics at each infection site differs depending upon location. Breakpoints used in mos t of the world comprise only one or two breakpoints, thus neglecting the infection site. 3,4 T h e N C C L S (Nat iona l C o m m i t t e e for Clinical Labora tory Standards) breakpoints extensively used in Japan ~,6 were determined on the available data, such as clinical dose and pharmacological kinetics, f rom American studies and are, therefore, not suitable for Japanese due to differing dose schedules.The breakpoints for Japanese should be investigated on the basis of the clinical

International symposium on chloramphenicol-thiamphenicol. Known and unknown aspects of drug-host interactions. January 10-12, 1973 Sils Maria, Switzerland

The conference was organised by the Section for Antimicrobial Therapy of the Paul Ehrlich Society for Chemotherapy, with the support of the firm Zambon of Milan, Italy. Participants from throughout the world took part in order to discuss the properties of Thiamphenicol (TAP) und Chloramphenicol (CAP) with particular reference to the haematological side effects, especially aplasia. CAP has more marked irreversible toxic effects than TAP. Investigations on the pharmacokinetics were also reported, in particular the renal insufficiency. Sufficiently comprehensive clinical data were not presented on TAP.