Combination Therapy for Mycoplasma genitalium, and New Insights Into the Utility of parC Mutant Detection to Improve Cure.

BACKGROUND: Mycoplasma genitalium (MG) infection is challenging to cure because of rising antimicrobial resistance and limited treatment options. METHODS: This was a prospective evaluation of the efficacy and tolerability of resistance-guided combination antimicrobial therapy for MG treatment at Melbourne Sexual Health Centre (August 2019-December 2020). All patients received 7 days of doxycycline before combination therapy based on the macrolide-resistant profile. Macrolide-susceptible infections received combination doxycycline + azithromycin (1 g, day 1; 500 mg, days 2-4) and macrolide-resistant infections combination doxycycline + moxifloxacin (400 mg daily for 7 days). Adherence and adverse effects were recorded at test-of-cure, recommended 14-28 days after antimicrobial completion. Sequencing was performed to determine the prevalence of single nucleotide polymorphisms (SNPs) in the parC gene and their association with moxifloxacin treatment outcomes in macrolide-resistant infections. RESULTS: Of 100 patients with macrolide-susceptible MG treated with doxycycline + azithromycin, 93 were cured (93.0%; 95% confidence interval [CI], 86.1-97.1). Of 247 patients with macrolide-resistant MG receiving doxycycline + moxifloxacin, 210 were cured (85.0%; 95% CI, 80.0-89.2). parC sequencing was available for 164 (66%) macrolide-resistant infections; 29% had SNPs at parC S83 or D87 (23% S83I). The absence of SNPs at parC S83/D87 was associated with 98.3% cure (95% CI, 93.9-99.8) following doxycycline + moxifloxacin. The presence of the parC S83I-SNP was associated with failure in 62.5% (95% CI, 45.8-77.3). Side effects were common (40%-46%) and predominantly mild and gastrointestinal. CONCLUSIONS: Combination doxycycline + azithromycin achieved high cure for macrolide-susceptible infections. However, in the context of a high prevalence of the parC S83I mutation (23%) in macrolide-resistant infections, doxycycline + moxifloxacin cured only 85%. Infections that were wild-type for S83/D87 experienced high cure following doxycycline + moxifloxacin, supporting the use of a parC-resistance/susceptibility testing strategy in clinical care.

Comparative efficacy and safety of traditional Chinese patent medicine in the treatment of Mycoplasma pneumoniae pneumonia in children: A protocol for systematic review and meta-analysis.

BACKGROUND: Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory disease in children. Its incidence rate is increasing year by year. The drug resistance rate of macrolide antibiotics and other conventional treatment methods is higher, and there are limitations in clinical application. Traditional Chinese patent medicine (TCPM) is a powerful weapon to treat this disease. At present, there is no comparison of the safety and effectiveness of multiple TCPMs in the treatment of MPP in children. Therefore, we take the method of network meta-analysis to systematically compare the efficacy of various TCPMs in the treatment of this disease. METHODS: We will conduct comprehensive searches of Cochrane Library, PubMed, Web of Science, Clinical Trials, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese BioMedical Literature, Wanfang Database, and other electronic databases. The time frame is set from the establishment of the database to October 2020. All randomized controlled trials that meet the inclusion criteria will be included in this study. The 2 researchers will independently screen the literature according to the inclusion criteria, extract the data, and assess the bias risk of the included study. We will evaluate all the obtained data and evidence through Bayesian network meta-analysis, and use Stata 15.0 to process and analyze the data. RESULTS: Through this study, we will evaluate the efficacy and safety of a variety of TCPMs for the treatment of MPP in children. CONCLUSION: The purpose of this study is to provide a strong reference for clinical application of TCPMs in the treatment of MPP in children, and to provide an important basis for clinicians to make correct judgments and put forward accurate treatment plans. ETHICS AND DISSEMINATION: This review does not involve any human or animal experiments and therefore does not require ethical approval. INPLASY REGISTRATION NUMBER: INPLASY 2020100108.

A Common Practice of Widespread Antimicrobial Use in Horse Production Promotes Multi-Drug Resistance.

The practice of prophylactic administration of a macrolide antimicrobial with rifampin (MaR) to apparently healthy foals with pulmonary lesions identified by thoracic ultrasonography (i.e., subclinically pneumonic foals) is common in the United States. The practice has been associated epidemiologically with emergence of R. equi resistant to MaR. Here, we report direct evidence of multi-drug resistance among foals treated with MaR. In silico and in vitro analysis of the fecal microbiome and resistome of 38 subclinically pneumonic foals treated with either MaR (n = 19) or gallium maltolate (GaM; n = 19) and 19 untreated controls was performed. Treatment with MaR, but not GaM, significantly decreased fecal microbiota abundance and diversity, and expanded the abundance and diversity of antimicrobial resistance genes in feces. Soil plots experimentally infected with Rhodococcus equi (R. equi) and treated with MaR selected for MaR-resistant R. equi, whereas MaR-susceptible R. equi out-competed resistant isolates in GaM-treated or untreated plots. Our results indicate that MaR use promotes multi-drug resistance in R. equi and commensals that are shed into their environment where they can persist and potentially infect or colonize horses and other animals.

First Description of Macrolide-Resistant Mycoplasma pneumoniae in Adults with Community-Acquired Pneumonia in Italy.

BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP). This cross-sectional study aimed to determine the prevalence of macrolide-resistant M. pneumoniae strains in a convenience series of 234 adult hospitalised and nonhospitalised subjects with a diagnosis of CAP in January 2013 to April 2015 in South Italy. METHODS: Respiratory samples were subjected to real-time PCR. In M. pneumoniae-positive samples, domain V of 23S rRNA was sequenced to detect resistance-conferring point mutations. P1 major adhesion protein typing and multiple loci variable-number tandem repeat analysis (MLVA) were also performed. RESULTS: Of the 234 samples, 15 (6.4%) were positive for M. pneumoniae. Three of these had a macrolide-resistant genotype: two and one had A2063G and A2064G mutations, respectively. Fourteen of the 15 strains were subtyped: half had subtype 1 and half had subtype 2. Eight strains underwent MLVA profiling: one each had the J, A, and Z type. The remainder was unclassifiable. CONCLUSIONS: This novel discovery of macrolide-resistant M. pneumoniae strains in adults with CAP in Italy suggests that there may be increasing circulation of these strains in the population. To facilitate rapid optimization of the antibiotic strategy in Italy, macrolide resistance should be monitored by a surveillance system that is based on molecular methods.

What not to do in acute otitis media: the top five recommendations proposed by the Italian Society of Preventive and Social Pediatrics.

INTRODUCTION: With the aim to reduce inappropriate procedures and antibiotic therapy in the management of acute otitis media (AOM) in children, the Italian Society of Preventive and Social Pediatrics (SIPPS) proposed a top five list of recommendations for clinical practice. Areas covered: AOM is one of the most frequent reasons for antibiotic prescription in pediatric age. The over-estimation of AOM is associated with inappropriate treatment, increased costs, adverse events and spread of antibiotic resistance. Thus, the most recent guidelines provided stringent diagnostic criteria and considered the 'watchful waiting' approach, limiting the immediate antibiotic therapy to a well-characterized subgroup of children. Expert commentary: The five recommendations proposed are: 1) Do not diagnose AOM without having documented the presence of middle ear effusion 2) Do not diagnose AOM without examining the entire tympanic membrane; 3) Do not treat immediately all cases of AOM with antibiotics; 4) Do not administer ear analgesic drops until examining the whole tympanic membrane 5) Do not use macrolides in the AOM therapy. This list of top five recommendations could be a novel tool to spread the key messages on the guidelines and to promote the correct diagnostic procedures as well as a rational use of antibiotics in children.

New treatment options for lower respiratory tract infections.

INTRODUCTION: Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are among the most frequent lower respiratory tract infections (LRTIs). They represent an increased morbidity and mortality rate in adults. Areas covered: This review describes recent advances regarding solithromycin, zabofloxacin and delafoxacin antibacterial agents that have been recently developed for treatment of CAP and in AECOPD. All of them have been introduced into phase III clinical trials. We will be summarising chemical structures, pharmacokinetics, antibacterial efficacy and toxicity of these agents. The manuscript has been prepared based on available scientific publications. Expert opinion: Novel agents of known antimicrobial classes have been developed that demonstrate treatment options in CAP and in AECOPD. Antimicrobials discussed in this review showed bactericide effect against major respiratory tract pathogens. Each has multiple targets in bacteria, thus enabling them for more potency, even against strains exhibiting resistance to commonly used antibiotics. Solithromycin, delafloxacin and zabofloxcian demonstrate broad-spectrum antibacterial activity together with other beneficial features like intracellular accumulation, anti-inflammatory effect and inhibition of biofilm production. These agents showed moderately severe or mild adverse events and demonstrated favourable tissue penetration. These features can make solithromycin, zabofloxacin and delafloxacin treatment options in LRTIs.

Solithromycin: A novel ketolide antibiotic.

PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed. SUMMARY: Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance. Phase III clinical trials of solithromycin demonstrated noninferiority of both oral and i.v.-to-oral regimens of 5-7 days' duration compared with moxifloxacin for patients with moderately severe CABP. Nearly one third of patients receiving i.v. solithromycin experienced infusion-site reactions. Although no liver-related adverse events were reported in patients receiving oral solithromycin, more patients receiving i.v.-to-oral solithromycin experienced asymptomatic, transient transaminitis, with alanine transaminase levels of >3 to >5 times the upper limit, compared with those treated with moxifloxacin. These results led the Food and Drug Administration to conclude that the solithromycin new drug application was not approvable as filed, adding that the risk of hepatotoxicity had not yet been adequately characterized. The agency further recommended a comparative study of patients with CABP to include approximately 9,000 patients exposed to solithromycin in order to exclude drug-induced liver injury events occurring at a rate of 1 in 3,000 with 95% probability. CONCLUSION: Solithromycin is a novel ketolide antibiotic with activity against a broad spectrum of intracellular organisms, including those displaying macrolide resistance. While demonstrating noninferiority to a current first-line agent in the treatment of CABP, concerns for drug-induced liver injury and infusion-site reactions have placed its regulatory future in doubt.

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

BACKGROUND: Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. METHODOLOGY/PRINCIPAL FINDINGS: Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

SOLITAIRE-IV: A Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous-to-Oral Solithromycin to Intravenous-to-Oral Moxifloxacin for Treatment of Community-Acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin, a novel macrolide antibiotic with both intravenous and oral formulations dosed once daily, has completed 2 global phase 3 trials for treatment of community-acquired bacterial pneumonia. METHODS: A total of 863 adults with community-acquired bacterial pneumonia (Pneumonia Outcomes Research Team [PORT] class II-IV) were randomized 1:1 to receive either intravenous-to-oral solithromycin or moxifloxacin for 7 once-daily doses. All patients received 400 mg intravenously on day 1 and were permitted to switch to oral dosing when clinically indicated. The primary objective was to demonstrate noninferiority (10% margin) of solithromycin to moxifloxacin in achievement of early clinical response (ECR) assessed 3 days after first dose in the intent-to-treat (ITT) population. Secondary endpoints included demonstrating noninferiority in ECR in the microbiological ITT population (micro-ITT) and determination of investigator-assessed success rates at the short-term follow-up (SFU) visit 5-10 days posttherapy. RESULTS: In the ITT population, 79.3% of solithromycin patients and 79.7% of moxifloxacin patients achieved ECR (treatment difference, -0.46; 95% confidence interval [CI], -6.1 to 5.2). In the micro-ITT population, 80.3% of solithromycin patients and 79.1% of moxifloxacin patients achieved ECR (treatment difference, 1.26; 95% CI, -8.1 to 10.6). In the ITT population, 84.6% of solithromycin patients and 88.6% of moxifloxacin patients achieved clinical success at SFU based on investigator assessment. Mostly mild/moderate infusion events led to higher incidence of adverse events overall in the solithromycin group. Other adverse events were comparable between treatment groups. CONCLUSIONS: Intravenous-to-oral solithromycin was noninferior to intravenous-to-oral moxifloxacin. Solithromycin has potential to provide an intravenous and oral option for monotherapy for community-acquired bacterial pneumonia. CLINICAL TRIALS REGISTRATION: NCT01968733.

Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL).

BACKGROUND: Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality, and treatment recommendations, each with specific limitations, vary globally. We aimed to compare the efficacy and safety of solithromycin, a novel macrolide, with moxifloxacin for treatment of CABP. METHODS: We did this global, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial at 114 centres in North America, Latin America, Europe, and South Africa. Patients (aged ≥18 years) with clinically and radiographically confirmed pneumonia of Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV were randomly assigned (1:1), via an internet-based central block randomisation procedure (block size of four), to receive either oral solithromycin (800 mg on day 1, 400 mg on days 2-5, placebo on days 6-7) or oral moxifloxacin (400 mg on days 1-7). Randomisation was stratified by geographical region, PORT risk class (II vs III or IV), and medical history of asthma or chronic obstructive pulmonary disease. The study sponsor, investigators, staff, and patients were masked to group allocation. The primary outcome was early clinical response, defined as an improvement in at least two of four symptoms (cough, chest pain, sputum production, dyspnoea) with no worsening in any symptom at 72 h after the first dose of study drug, with a 10% non-inferiority margin. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT-01756339. FINDINGS: Between Jan 3, 2013, and Sept 24, 2014, we randomly assigned 860 patients to receive solithromycin (n=426) or moxifloxacin (n=434). Patients were followed up to days 28-35 after first dose. Solithromycin was non-inferior to moxifloxacin in achievement of early clinical response: 333 (78·2%) patients had an early clinical response in the solithromycin group versus 338 (77·9%) patients in the moxifloxacin group (difference 0·29, 95% CI -5·5 to 6·1). Both drugs had a similar safety profile. 43 (10%) of 155 treatment-emergent adverse events in the solithromycin group and 54 (13%) of 154 such events in the moxifloxacin group were deemed to be related to study drug. The most common adverse events, mostly of mild severity, were gastrointestinal disorders, including diarrhoea (18 [4%] patients in the solithromycin group vs 28 [6%] patients in the moxifloxacin group), nausea (15 [4%] vs 17 [4%] patients) and vomiting (ten [2%] patients in each group); and nervous system disorders, including headache (19 [4%] vs 11 [3%] patients) and dizziness (nine [2%] vs seven [2%] patients). INTERPRETATION: Oral solithromycin was non-inferior to oral moxifloxacin for treatment of patients with CABP, showing the potential to restore macrolide monotherapy for this indication. FUNDING: Cempra.

In vitro and in vivo models of drug ototoxicity: studying the mechanisms of a clinical problem.

INTRODUCTION: Drug ototoxicity represents one of the main preventable causes of deafness. Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, antimalarial medications, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and most recently described, acetaminophen when abused with narcotic medication. These medications are prescribed despite their side effects, which includes inner ear toxicity, because they are life-saving drugs or there is a lack of better treatment. AREAS COVERED: This review will discuss in vitro and in vivo models of ototoxicity highlighting recently published ototoxicity research. The reader will learn the strengths and limitations of different ototoxicity models and what molecular insights have been gained from their application. A better understanding of the cellular mechanisms of these ototoxins will help in the discovery of ways to prevent and treat hearing loss associated with ototoxic medications. EXPERT OPINION: There are benefits to both in vitro and in vivo models of ototoxicity. Research of a particular medication and its ototoxic mechanisms should draw from several models, enabling a better answer to the clinical question of prevention and treatment of inner ear drug toxicity.

Reacciones adversas psiquiátricas asociadas a nuevos macrólidos. A propósito de tres casos / Psychiatric adverse reactions associated to new macrolides. Three case reports

Los macrólidos representan el 10-15% del mercado mundial de antibióticos orales. Son uno de los grupos de antibióticos más seguros; las reacciones adversas graves son muy raras. Pueden producir reacciones gastrointestinales, hepatotoxicidad y ototoxicidad. Además, las reacciones psiquiátricas se encuentran entre los efectos adversos esporádicamente asociados con su administración, aunque su mecanismo no está bien establecido. Casos descritos en la Food and Drug Administration (FDA) de EE.UU. muestran que la claritromicina y el ciprofloxacino son los antibióticos más frecuentemente asociados con el desarrollo de manía. Este término ha sido denominado antibiomanía. Presentamos tres casos clínicos vistos en una consulta de Atención Primaria en el período de un año con cuadros similares de hiperactividad y agresividad, coincidiendo con la administración de antibióticos de la familia de los macrólidos (AU)

Macrolides represent the 10-15% of the world-wide market of oral antibiotics. They are one of the safer groups of antibiotics, being the severe adverse reactions very rare. They can produce gastrointestinal reactions, hepatotoxicity and ototoxicity. The psychiatric reactions are found sporadically among the adverse effects. Cases reported to the FDA showed that clarithromycin and ciprofloxacin are the most frequent antibiotics associated with the development of mania. The syndrome has been termed antibiomania. We present three clinical cases seen in a Primary Care office in the last year with similar pictures of hyperactivity and aggressiveness coinciding with the administration of antibiotics of the family of the macrolides (AU)

Moxidectin interference on sexual behavior, penile erection and hypothalamic GABA levels of male rats.

The moxidectin (MXD) is an antiparasitic drug used in domestic animals. The mechanism of action, in mammals, involves GABA, a neurotransmitter with an important role in the sexual behavior control. Presently, the effects of 0.2 mg/kg therapeutic dose were studied on sexual behavior, sexual motivation, penile erection and central GABA levels. Sexual behavior results showed increased latencies to the first mount and intromission as well as in inter-intromission interval; a reduction in total mounts was detected on the drug post-treatment. No difference was observed between sexual motivation of control and experimental animals. MXD treatment reduced penile erection and hypothalamic GABA levels. The results suggest that MXD reduced sexual behavior and penile erection by an action on the hypothalamic GABA system. Probably, the lack of effects in the motivational test and the increased mount and intromission latencies as well as decreased total mounts could be explained as a consequence of reduced male rat erection process.

Real-life treatment of acute exacerbations of chronic bronchitis with moxifloxacin or macrolides: a comparative post-marketing surveillance study in general practice.

OBJECTIVE: To compare the real-life treatment of acute exacerbations of chronic bronchitis (AECBs) using moxifloxacin tablets or one of the oral macrolides azithromycin, clarithromycin or roxithromycin in terms of symptom relief, time until improvement and cure, overall efficacy and tolerability. METHODS: This prospective, non-interventional, multicentre study included out-patients with AECB whose last exacerbation was treated with a macrolide. The current AECB was treated either with moxifloxacin or with one of the macrolides azithromycin, clarithromycin or roxithromycin. Data were obtained on the patient's characteristics, disease and treatment history, the course of the current AECB including time to improvement and cure, and the final assessments of efficacy and tolerability. All adverse events were recorded in patients treated with moxifloxacin; for patients receiving macrolides, only drug-related adverse events were reported. RESULTS: 464 physicians treated 904 patients with moxifloxacin and 846 patients with one of the macrolides. Age, sex and body mass index were well matched between the two treatment groups. However, more moxifloxacin than macrolide patients presented with a generally bad condition (62.8% vs 48.6%). About 42% of patients in both groups had had chronic bronchitis for 1-5 years, and about 27% for 5-10 years. The mean number of AECBs in the previous 12 months was 2.7 and 2.6, respectively. Moxifloxacin was administered to most patients for 5 (43.8%) or 7 days (42.4%). Patients in the macrolide group were treated in most cases with clarithromycin 500 mg for 4-7 days, roxithromycin 300 mg for 6-7 days or azithromycin 500 mg for 3 days. Physicians assessed overall efficacy and tolerability as 'very good' or 'good' in 96.1% and 98.1%, respectively, of moxifloxacin-treated patients and in 67.5% and 91.7%, respectively, of macrolide-treated patients. The mean duration until improvement and cure of AECB was 3.2 days (+/- SD 1.5) and 6.2 days (+/- 2.6) in moxifloxacin-treated patients compared with 4.5 days (+/- 1.8) and 7.5 days (+/- 3.0) in macrolide-treated patients (p < 0.0001). CONCLUSION: The results of this study conducted under real-life treatment conditions in patients with AECBs who were previously treated with a macrolide showed faster symptom relief and higher recovery rates with moxifloxacin compared with macrolides. The two treatment groups had comparably good safety and tolerability profiles.

Efficacy and safety of oral telithromycin once daily for 5 days versus moxifloxacin once daily for 10 days in the treatment of acute bacterial rhinosinusitis.

OBJECTIVE: To compare the clinical and bacteriologic efficacy and safety of short-duration treatment with telithromycin given for 5 days with moxifloxacin given for 10 days in adults with acute bacterial rhinosinusitis (ABRS). STUDY DESIGN: In this prospective, double-blind, parallel-group, randomized, multicenter study, adult patients (N = 349) with ABRS were randomized to oral telithromycin (800 mg once daily for 5 days) or to oral moxifloxacin (400 mg once daily for 10 days) and followed for 31 to 36 days. Clinical outcome was determined by the investigator at the posttherapy/test of cure (TOC) visit. Bacteriologic outcome was determined by comparing cultures taken at the pretreatment visit with cultures obtained at the posttherapy/TOC visit. The primary objective was to demonstrate equivalence of clinical cure rates in the per-protocol population between treatment groups at the posttherapy/TOC visit. RESULTS: Clinical success at TOC (primary endpoint) was achieved in 87.4% of patients in the telithromycin group compared with 86.9% for moxifloxacin (per-protocol patients; 0.5% difference between treatment groups; 95% confidence interval [CI], -8.1, 9.2; P = 0.8930). The bacteriologic success rates were 94.1% and 93.9%, respectively (0.2% difference between treatment groups; 95% CI, -14.2, 14.5; P = 0.9734). Overall treatment-emergent adverse events for both drugs (mostly gastrointestinal) were mild to moderate in intensity. CONCLUSION AND SIGNIFICANCE: The clinical and bacteriologic efficacy of telithromycin 800 mg once daily for 5 days was equivalent to that of moxifloxacin 400 mg once daily for 10 days, establishing telithromycin as an important treatment option for ABRS.

Drug interactions of clinical significance for the dermatologist: recognition and avoidance.

While it would be impossible for any dermatologist to remember all potential drug interactions, knowledge of the mechanisms of drug interactions can help reduce the risk of serious adverse outcomes. Most drugs are associated with interactions but the majority do not produce significant outcomes. Dealing with drug interactions is a challenge in all clinical practice, including dermatology. New information continues to appear, and dermatologists need to know about the drugs they use.This article focuses on the mechanisms of drug interactions. In particular, the life of a drug in terms of absorption, distribution, metabolism and excretion are reviewed with the focus on points of importance and relevance to drug interactions. The most clinically important drug interactions in dermatological practice are caused by alterations in drug metabolism. The contributions of P-glycoprotein, pharmacogenetic variation and genetic polymorphisms to drug interactions are highlighted, and the best evidence for drug interactions involving drug classes relevant to the dermatologist is presented. Since the initial evidence for clinically relevant drug interactions comes from case reports, prescribing physicians can have a major role in collating information on interactions. By understanding the mechanisms behind drug interactions and staying alert for toxicities, we can help make drug therapy safer and reduce the fear of drug interactions.

[Antibiotic-associated diarrhea in light of personal observations]. / Zespoly biegunkowe po antybiotykoterapii w swietle wlasnych obserwacji.

Examination was performed in a group of 539 adult patients with diarrhea admitted to the Department of Infectious Diseases in Gdansk from 1991 to 1994. The group of 17 patients with antibiotic-associated colitis (AAC) was analysed. The antibiotics responsible for AAC were lincosamides, cephalosporins and penicillins. AAC was diagnosed by anamnesis, medical examination and detection of toxin A Clostridium difficile in stool samples. The contrast enema, colonoscopy and histopathological examination of colon mucosa were performed only in severe, protracted cases. The course of disease was mild in 2 cases, moderate in 13 and severe in 2 patients. Relapses of AAC were observed in 2 cases. Initial treatment of AAC included discontinuation of the antibiotic therapy that precipitated the disease and the replacement of fluid and electrolyte losses. Moreover, oral metronidazole and oral vancomycin were administered. All patients made a complete recovery.