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The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study is the only ongoing nationwide antibiotic resistance surveillance program specific to ocular pathogens.
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Cryptosporidium parvum, the protozoan responsible for cryptosporidiosis, continues to defy eradication with existing therapies. A review of the anticryptosporidial activity of several drugs in the dexamethasone-immunosuppressed rat model illustrates the multitude of factors that may contribute to the difficulty of assessing a drug's therapeutic efficacy against the protozoan and provides possible explanation for drug failure at the level of host-parasite interaction.
Although T. pallidum remains sensitive to penicillin and certain other antibiotics, azithromycin resistance in T. pallidum has emerged and is increasing in the United States, Canada, and Ireland. This poses clinical and public health challenges, and indicates a need for further antibiotic drug development and surveillance for resistance in T. pallidum. If azithromycin is used to treat syphilis, clinicians and public health practitioners should remain vigilant for treatment failures.
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Overall, 22/25 (88%) foals in the placebo group recovered without the need for treatment. The proportion of foals that had evidence of disease progression did not differ significantly between the treatment groups (P > .05). Although the median duration of treatment was significantly (P < .05) shorter in foals treated with azithromycin-rifampin (46 days) compared with foals treated with the placebo (73 days), the time frame of ultrasonographic lesion resolution did not differ significantly between the treatment groups.
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Infections with Salmonella are an important public health problem worldwide. On a global scale, it has been appraised that Salmonella is responsible for an estimated 3 billion human infections each year. The World Health Organization (WHO) has estimated that annually typhoid fever accounts for 21.7 million illnesses (217,000 deaths) and paratyphoid fever accounts for 5.4 million of these cases. Infants, children, and adolescents in south-central and South-eastern Asia experience the greatest burden of illness. In cases of enteric fever, including infections with S. Typhi and S. Paratyphi A and B, it is often necessary to commence treatment before the results of laboratory sensitivity tests are available. Hence, it is important to be aware of options and possible problems before beginning treatment. Ciprofloxacin has become the first-line drug of choice since the widespread emergence and spread of strains resistant to chloramphenicol, ampicillin, and trimethoprim. There is increase in the occurrence of strains resistant to ciprofloxacin. Reports of typhoidal salmonellae with increasing minimum inhibitory concentration (MIC) and resistance to newer quinolones raise the fear of potential treatment failures and necessitate the need for new, alternative antimicrobials. Extended-spectrum cephalosporins and azithromycin are the options available for the treatment of enteric fever. The emergence of broad spectrum β-lactamases in typhoidal salmonellae constitutes a new challenge. Already there are rare reports of azithromycin resistance in typhoidal salmonellae leading to treatment failure. This review is based on published research from our centre and literature from elsewhere in the world. This brief review tries to summarize the history and recent trends in antimicrobial resistance in typhoidal salmonellae.
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In vitro susceptibility to erythromycin, azithromycin, penicillin G, ceftriaxone and ceftibuten was investigated in 190 Streptococcus pyogenes strains isolated over a 4-year period (1991-1994) from patients attending a university hospital located in central Italy. The rate of susceptibility to macrolide antibiotics of the S. pyogenes strains showed a progressive decrease (from 90.3% in 1991 to 79.5% in 1994), while all strains were susceptible to the three beta-lactam antibiotics. Owing to the reduced prevalence of macrolide-susceptible S. pyogenes strains, in vitro susceptibility testing of streptococcal isolates appears to be always necessary before starting a macrolide-based chemotherapy. Concerning beta-lactams, ceftriaxone presented minimum inhibitory concentrations (MIC) always equal to or lower than those of penicillin G, while the oral long-acting cephalosporin, ceftibuten, had MICs higher than those of the other beta-lactams, although in the susceptible range. Results of in vitro susceptibility testing are discussed in relation to their implications for antimicrobial chemotherapy of S. pyogenes infections.
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Several clinically significant drug interactions have been identified since the approval of erythromycin. These interactions usually were related to the inhibition of the cytochrome P450 enzyme systems, which are responsible for the metabolism of many drugs. The decreased metabolism by the macrolides has in some instances resulted in potentially severe adverse events. The development and marketing of newer macrolides are hoped to improve the drug interaction profile associated with this class. However, this has produced variable success. Some of the newer macrolides demonstrated an interaction profile similar to that of erythromycin; others have improved profiles. The most success in avoiding drug interactions related to the inhibition of cytochrome P450 has been through the development of the azalide subclass, of which azithromycin is the first and only to be marketed. Azithromycin has not been demonstrated to inhibit the cytochrome P450 system in studies using a human liver microsome model, and to date has produced none of the classic drug interactions characteristic of the macrolides.
As part of the ongoing multinational SENTRY antimicrobial resistance surveillance program, a total of 1,047 respiratory tract isolates of Streptococcus pneumoniae, 845 from 27 United States medical centers and 202 from seven Canadian institutions, were collected between February and June 1997 and characterized in a central laboratory. In the United States, the overall percentages of penicillin-intermediate strains and strains with high-level resistance to penicillin were 27.8% and 16.0%, respectively. In Canada, these values were 21.8% and 8.4%, respectively. Among the 31 centers in the United States and Canada that contributed at least 19 isolates, the combined rate of intermediate plus resistant strains varied between 24.0% and 67.8%. The in vitro activity of 19 other antimicrobials was assessed against all study isolates. Overall rates of resistance among selected agents in the United States and Canada, respectively, were as follows: amoxicillin, 18.1% and 10.5%; cefaclor, 38.3% and 26.2%; cefuroxime, 19.5% and 12.9%; cefpodoxime, 18.6% and 11.4%; cefepime, 8.2% and 4.5%; cefotaxime, 4.0% and 3.0%; macrolides (i.e., erythromycin, azithromycin, and clarithromycin), 11.7%-14.3% and 5.0%-7.4%; clindamycin, 3.5% and 3.5%; chloramphenicol, 3.9% and 4.0%; tetracycline, 10.2% and 10.9%; and trimethoprim-sulfamethoxazole, 19.8% and 15.8%.
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A first round of antibiotic MDA was conducted in the highly trachoma endemic county of Mayom, Unity state, from June to August 2010. A core team of seven staff delivered the intervention, including recruitment and training of 44 supervisors and 542 community drug distributors. Using an ingredients approach, financial and economic costs were captured from the provider perspective in a detailed costing database. Overall, 123,760 individuals were treated for trachoma, resulting in an estimated treatment coverage of 94%. The economic cost per person treated was USD 1.53, excluding the cost of the antibiotic azithromycin. Ninety four per cent of the delivery costs were recurrent costs, with personnel and travel/transport costs taking up the largest share.
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Plasmodium vivax is the most prevalent malaria infection and is an important cause of morbidity in Central and South America and Asia. P. vivax is generally sensitive to the common antimalarial drugs but high level resistance to chloroquine and/or pyrimethamine has been documented in some geographic locations. In the studies reviewed here, the therapeutic responses to antimalarial and antibacterial drugs in vivax malaria have been assessed in the Bangkok Hospital for Tropical Diseases. The evaluated drugs consisted of the eight most widely used antimalarial drugs and anti-bacterial drugs that possess antimalarial activities (tetracycline, doxycycline, clindamycin or azithromycin). The activities of these drugs in descending order of parasite clearance times were artesunate, artemether, chloroquine, mefloquine, quinine, halofantrine, primaquine, followed by the antibacterial drugs and lastly sulfadoxine-pyrimethamine. Clinical responses to sulfadoxine-pyrimethamine were also poor with evidence of high grade resistance in 42% of the patients. Of the four antibacterial drugs, clindamycin was more effective than azithromycin and can be an alternative to the tetracyclines. Except for chloroquine and mefloquine which have long plasma half lives and may therefore suppress first relapses, the cumulative cure rates for the short acting antimalarial drugs were similar. Double infection with Plasmodium falciparum was common and usually manifested 3-4 weeks following clearance of vivax malaria. The prevalence of cryptic falciparum malaria was 8-15% and was higher in patients treated with less potent antimalarial drugs. Follow-up studies have revealed that the relapse time in Thai patients with vivax malaria is on average only 3 weeks, but can be suppressed by the slowly eliminated antimalarial drugs such as chloroquine and mefloquine. For accurate comparison of relapse/recrudescence rates in vivax malaria, at least 2 month's follow-up is required. It can be concluded that in malarious areas of Thailand, double infection with P. falciparum and P. vivax is common affecting at least 25% of the patients and usually manifests as sequential illnesses. P. vivax in Thailand is sensitive to chloroquine but has acquired high grade resistance to sulfadoxine-pyrimethamine.
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The present investigation was a self-paired case study of 33 patients with ENP. A comparison was performed between patients before and after treatment with azithromycin for 8 weeks. The patients were subjected to clinical examinations, staging (three-dimensional imaging by endoscopy), application of the questionnaire, and biopsy of nasal polyps at the beginning and at the end of the treatment.
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A novel oral, extended-release, microsphere formulation of azithromycin (AZSR) was developed to improve the gastrointestinal tolerability profile while allowing administration of an entire treatment course of azithromycin in a single dose. Several phase I clinical pharmacology studies were conducted to (i) identify a well-tolerated single-dose formulation that met a predefined exposure target; and (ii) evaluate the effect of food and antacid on the absorption of this formulation. Of these, five pivotal studies are described here.
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The median (range) "time to healing" in weeks for 43 patients who had surgery alone was: incision and drainage (I&D)/curettage 6 (1-72) (n = 10); excision 3 (1-28) (n = 22); and from the last operation of multiple (repeat) surgery 3 (1-40) (n = 11). For 25 patients who required chemotherapy in addition to surgery, the median (range) "time to healing" in weeks was I&D/curettage 10 (1-40) (n = 17), excision 14 (8-20) (n = 2) and multiple surgery 29 (2-88) (n = 6).
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Scrub typhus is an acute febrile illness caused by the intracellular parasite Orientia tsutsugamushi. Although most cases present with mild symptoms and signs and recover spontaneously, some cases can be severe with multi-organ dysfunction and a protracted course, which may be fatal if left untreated. Apart from fever and constitutional symptoms, atypical presentations allow this disease to mimic several common conditions. We report a case of scrub typhus in an 18-year-old male who presented with severe polyarthritis involving all large joints and a massive lower gastrointestinal bleed from ulcers in the terminal ileum, secondary to vasculitis in the small bowel. This combination of pathologies has not previously been reported in cases of scrub typhus. The patient improved following surgical intervention and specific anti-rickettsial therapy with azithromycin.
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The study sought evidence for changes in the proportions of antibiotic resistant strains among isolates of Salmonella enterica serovar Typhi (S. typhi) and Salmonella enterica serovar Paratyphi (S. paratyphi) between 2005 and 2012.
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In this double-blind, randomised trial conducted in 22 centres in the USA, azithromycin given over five days, as a once-a-day regimen, (500 mg on day 1, 250 mg on days 2-5) was compared with cephalexin (500 mg b.i.d.) given for ten days in the treatment of patients with skin and skin structure infections. A total of 366 patients entered the study and 179 of these were eligible for the efficacy analysis. The overall clinical response to azithromycin was 94.0%, compared with 95.8% for cephalexin. The clinical cure rates were 53.0% for azithromycin and 59.4% for cephalexin; the respective improvement rates were 41.0% and 36.5%. Distribution of response (cured, improved, failed) was similar in each group (p = 0.37). The bacteriological eradication rate for azithromycin-treated patients was 94.2% and for cephalexin-treated patients was 90.3% (p = 0.34). Clinical and bacteriological response was similar in each group for all primary diagnoses. The two antibiotics were well tolerated, the overall incidence of side effects being 13.7% with approximately 60% due to gastrointestinal disturbances. In all but one case (cephalexin) the severity of the reported side effects was mild or moderate. Six patients withdrew from the study due to treatment-related events; five had been treated with azithromycin and one with cephalexin. In summary, a five-day, once-daily regimen of azithromycin was as effective as a ten-day, twice-daily regimen of cephalexin in the treatment of patients with skin and skin structure infections.
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In capillary electrophoresis (CE), separation of enantiomers of a chiral compound can be achieved through the chiral interactions and/or complex formation between the chiral selector and the enantiomeric analytes on leaving their diastereomeric forms with different stability constants and hence different mobilities. A great number of chiral selectors have been employed in CE and among them macrocyclic antibiotics exhibited excellent enantioselective properties towards a wide number of racemic compounds. The use of azithromycin (AZM) as a chiral selector has not been reported previously. This work reports the use of AZM as a chiral selector for the enantiomeric separations of five chiral drugs and one amino acid (tryptophan) in CE. The enantioseparation is carried out using polar organic mixtures of acetonitrile (ACN), methanol (MeOH), acetic acid and triethylamine as run buffer. The influences of the chiral selector concentration, ACN/MeOH ratio, applied voltage and capillary temperature on enantioseparation are investigated. The results show that AZM is a viable chiral selector in CE for the enantioseparation of the type of chiral drugs investigated.
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Acne affects a large number of young adults, including women, who often present with facial as well as truncal involvement. Systemic antimicrobial agents currently used for the reduction of inflammatory papules and cysts require frequent administration and are sometimes associated with uncomfortable side-effects contributing to a decrease in compliance.
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Sixteen communities in Tanzania with trachoma prevalence rates between 10% and 20%.
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The objective of this study was to evaluate the cost-effectiveness of universal screening and azithromycin-based prophylaxis against no intervention for Chlamydia trachomatis infection among women seeking induced abortions.
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Current medical literature, including abstracts presented at international meetings, is reviewed. References were identified through MEDLINE, Current Contents, and published meeting abstracts.
Obliterative bronchiolitis (OB) is a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Our objective was to perform a systematic review and meta-analysis of the impact of azithromycin on change in forced expiratory volume in 1 second (FEV1). We searched MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL and Scopus databases and included studies that compared azithromycin with placebo or no intervention in the treatment of OB or bronchiolitis obliterans syndrome (BOS) in patients who had undergone allogeneic HSCT. Ninety-one unique publications were identified, and 4 studies met inclusion criteria, with a total of 90 patients. Changes in FEV1 were measured between 12 and 24 weeks after initiation of treatment. The meta-analysis demonstrated a mean increase in FEV1 of 30 mL (95% confidence interval, -260 to +330 mL; P = .82) after initiation of azithromycin. One patient death was reported but not attributed to azithromycin therapy. In conclusion, current evidence can neither support nor refute the use of azithromycin in the treatment of patients who develop OB/BOS after HSCT. Further studies are needed to determine whether azithromycin is beneficial for the treatment of OB/BOS in this setting.
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A prospective cohort study was made of 386 first-grade primary-school children in Oman with active trachoma and 386 matched controls without trachoma. All children were educated about trachoma prevention. In addition, trachoma cases were treated with a single dose of oral azithromycin (20 mg/kg). Trachoma status was evaluated after 6 weeks, 6 months and 12 months. The follicles and inflammatory signs of active trachoma resolved 6 weeks or more after azithromycin treatment. The protection against subsequent trachoma infection cycles was optimal at 6 months (85.2% of cases, 99.0% of controls infection-free) but declined at 12 months (66.7% of cases, 98.2% of controls infection-free). Clinical evaluation seems to be a useful tool to evaluate the response of azithromycin to active trachoma cases in schoolchildren in a country with limited resources.
Determine the prevalence of Campylobacter in stool cultures from patients with gastroenteritis and study their microbiological, epidemiological, clinical, and therapeutic profiles, as well as associated complications.
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We investigated the susceptibility to antibacterial agents, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes against 270 strains of Streptococcus pneumoniae isolated from medical facilities in Gifu and Aichi prefectures between October 2011 and April 2012. These results were compared with those against S. pneumoniae isolated in 2008-2009 and 2010-2011. The number of gPSSP with 3 normal PBP genes, gPISP with 1 or 2 normal PBP genes and gPRSP with 3 abnormal genes isolated in 2011-2012 was 15 (5.6%), 162 (60.0%) and 93 (34.4%) strains, respectively. Compared with those isolated in 2008-2009 and 2010-2011, the numbers of gPRSP were decreasing. On the other hand, the isolates with no macrolide-resistant gene, only mefA, only ermB, and both mefA and ermB were 16 (5.9%), 75 (27.8%), 153 (56.7%) and 26 (9.6%). Compared with those isolated in 2008-2009 and 2010-2011, the numbers of isolates with ermB, which was usually associated with high-level resistance, were increasing. The prevalent pneumococcal serotypes in children were type 3 (14.4%), following by type 15 and 19F (9.3%). The coverages of 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were calculated as 22.9% and 49.2%, respectively. The coverages of PCV7 and PCV13 in gPRSP isolated from children were 47.7% (21/44 strains) and 72.7% (32/44 strains). The MIC90 of each antibacterial agent was as follows; 0.125pg/mL for imipenem, panipenem and garenoxacin, 0.25 μg/mL for meropenem and doripenem, 0.5 μg/mL for cefditoren, moxifloxacin and tosufloxacin, 1 μg/mL for amoxicillin, clavulanic acid/amoxicillin, cefteram, cefcapene and ceftriaxone, 2 μg/mL for benzylpenicillin, ampicillin, sulbactam/ampicillin, piperacillin, tazobactam/piperacillin and levofloxacin, 4 μg/mL for cefdinir, flomoxef and pazufloxacin, 16 μg/mL for minocycline, > 64 μg/mL for clarithromycin and azithromycin, and these MIC90s were about the same as those in 2010-2011.
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The prevention of malaria in travelers is becoming a more challenging clinical and public health problem because of the global development of drug-resistant Plasmodium strains of malaria and the increasing popularity of travel to exotic locales. Travelers can reduce their risk of acquiring malaria by using bed netting, wearing proper clothing and applying an insect repellent that contains N,N-diethyl-meta-toluamide. Chloroquine, once the standard agent for weekly malaria prophylaxis, is no longer reliably effective outside the Middle East and Central America because of the emergence of resistant Plasmodium falciparum strains. Mefloquine is now the most effective and most recommended antimalarial agent on the U.S. market; however, the side effects of this agent have begun to limit its acceptance. Doxycycline is effective for malaria prophylaxis in travelers who are unable to take mefloquine. Daily proguanil taken in conjunction with weekly chloroquine is an option for pregnant patients traveling to sub-Saharan Africa. Terminal prophylaxis with two weeks of primaquine phosphate can eliminate an asymptomatic carrier state and the later development of malaria in newly returned long-term travelers with probable exposure to Plasmodium vivax or Plasmodium ovale. Travelers who elect not to take an antimalarial agent or who are at high risk for malaria and are more than 24 hours from medical care can use self-treatment regimens such as those featuring pyrimethamine-sulfadoxine. Conventional agents may be contraindicated in certain travelers, especially pregnant women and small children, and several prophylactic agents are not available in the United States. Azithromycin and a number of malaria vaccines are currently under investigation.