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PubMed1996

Dirithromycin: a new macrolide.

OBJECTIVE: To review the clinical microbiology and therapeutic use of dirithromycin, emphasizing comparative data between dirithromycin and the standard macrolide erythromycin, as well as clarithromycin and azithromycin. DATA SOURCES: A MEDLINE search of English-language literature during the years 1966-1996, and an extensive review of journals were conducted to prepare this article. DATA EXTRACTION: The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open and controlled studies. Controlled single- or double-blind studies were evaluated to assess the efficacy of dirithromycin in the treatment of various upper and lower respiratory tract infections, as well as skin and soft tissue infections. DATA SYNTHESIS: The spectrum of activity of dirithromycin is similar to that of erythromycin, clarithromycin, or azithromycin, with some notable exceptions. Dirithromycin was more active in vitro against Campylobacter jejuni and Borrelia burgdorferi than was erythromycin or clarithromycin, but in general demonstrated less activity than erythromycin, clarithromycin, or azithromycin against a majority of microorganisms. The pharmacokinetic profile of dirithromycin offers the advantages of once-daily dosing and high and prolonged tissue concentrations; dosing adjustments are not needed in the elderly or in patients with renal or mild hepatic impairment. Clinical efficacy and bacteriologic eradication rates with dirithromycin and erythromycin are comparable for the treatment of respiratory and skin and soft tissue infections due to susceptible pathogens. Dirithromycin appears to have adverse effect profiles similar to those of the other macrolides, with reported problems most often related to the gastrointestinal tract. Dirithromycin does not seem to cause clinically important interactions with drugs such as theophylline, oral contraceptives, cyclosporine, or terfenadine. CONCLUSIONS: Dirithromycin offers some attractive pharmacokinetic properties. The long elimination half-life of dirithromycin allows once-daily dosing and higher and more prolonged tissue concentrations than are achievable with erythromycin. The spectrum of activity, adverse effect profile, clinical efficacy, and bacteriologic eradication rate of dirithromycin may be similar to those of erythromycin. No significant drug interactions with dirithromycin have been reported. Based on available data, dirithromycin may not offer any unique clinical advantage over clarithromycin or azithromycin. Future clinical trials may reveal a special role for dirithromycin in patient care.

Anti-Bacterial Agents↗

PubMed2000

Treatment of Chlamydia trachomatis infections in pregnant women.

The intent of this article is to provide an overview of the epidemiology and pharmacotherapy, including cost analyses, of Chlamydia trachomatis infections in pregnant women. Chlamydia is a common sexually transmitted infection. For pregnant women, there are concerns both for the mother (post-partum endometritis, horizontal transmission) and the newborn (conjunctivitis, delayed pneumonia). Therapeutic options are restricted because of the fetus and include multi-day treatment with erythromycin, amoxicillin, clindamycin or single dose azithromycin. Clinical cure rates with these options are 86, 92, 93 and 95%, respectively. Pharmacoeconomic analyses have been conducted to determine if the initial increase in acquisition cost of azithromycin (approximately 3-fold higher than erythromycin or amoxicillin) is offset by improvement in compliance and drug efficacy. Clindamycin has received little attention because of its expense (4-fold more than azithromycin). Analyses have been retrospective. As models incorporate more complications of failure to cure, azithromycin increasingly becomes more cost effective and is our recommended treatment.

Adult↗

PubMed2006

[Long term survival after Rhodococcus equi pneumonia in a patient with human immunodeficiency virus infection in the era of highly active antiretroviral therapy: case report and review].

Before highly active antiretroviral therapy (HAART) has become available, antibiotic treatment was usually unable to eradicate Rhodococcus (R.) equi infection in HIV-infected patients, although some clinical improvement could be observed in most cases. There are limited data on the outcome of treatment of R. equi pneumonia in the HAART era. We report on a 52-year-old HIV-infected man who presented in poor general condition with an extensive lung cavitation lesion caused by R. equi. The patient recalled exposure to horses on several occasions. R. equi was cultured from the sputum and the isolate was sensitive to imipenem vancomycin, co-trimoxazole, erythromycin, azithromycin, ciprofloxacin and rifampicin. The CD4+ lymphocyte count was 5 cells/mm3 (0.9%) and his plasma HIV-1 RNA viral load was 101000 copies/mL. The patient was successfully treated with a combination of antibiotics that included azithromycin both as part of an initial and suppressive regimen together with antiretroviral treatment. Surgery was not needed and the patient had no relapse for more than five years after the diagnosis and for more than 3 years of suppressive therapy discontinuation. Our literature search revealed 27 patients treated for R. equi infection in the HAART era. However, details on antimicrobial treatment were given in only 3 cases. The optimal drug regimen and duration of treatment for R. equi pneumonia have not yet been established. Because drug resistance may occur during single agent therapy, it has been suggested that at least two antibiotics to which R. equi is susceptible be given. The recommended choices usually include imipenem, antipseudomonal aminoglycosides, erythromycin or azithromycin, vancomycin, rifampin, and levofloxacin. To our knowledge this is the first documented case of long term remission of R. equi pneumonia in an HIV-infected man treated with azithromycin as part of his antibiotic regimen and HAART.

AIDS-Related Opportunistic Infections↗

PubMed1994

[Use of oral macrolide and azalide antibiotics in children with bronchopulmonary diseases].

The therapeutic efficacy of oral macrolides (erythromycin base and midekamycin, macropen) and azalides (azithromycin, sumamed) in the treatment of children with acute and chronic (during the aggravation) bronchopulmonary diseases was studied. The main etiological factors of acute and chronic pneumonia were Streptococcus pneumoniae and Haemophilus influenzae. The proportion of Staphylococcus aureus was high in infants with acute pleuropulmonary inflammations. The susceptibility of the isolates to the antibiotics was found to be high. The results of the trials showed that erythromycin, macropen and azithromycin were efficient in the treatment of acute and chronic pneumonia. The foci of acute pneumonia dissolved after oral administration of the drugs within the same periods as after the use of other parenteral antibiotics. The comparative estimation of the drug efficacy revealed that azithromycin was more active. The ease of the azithromycin administration (in the form of a suspension) in infants and children once a day for a shorter treatment course up to 5 days, high efficacy and no adverse reactions permitted to consider the antibiotic as the most promising antibacterial agent for the treatment of respiratory infections in children in hospitals and outpatient departments.

Administration, Oral↗

PubMed1997

Assessment of the palatability of beta-lactamase-resistant antibiotics in children.

OBJECTIVES: To evaluate the palatability of antibiotics effective against beta-lactamase-producing bacteria in children and to compare the results obtained with those obtained in adults. DESIGN: A taste test of 4 antibiotic suspensions: a combination of amoxicillin and clavulanic acid (banana), azithromycin (cherry), clarithromycin (wild fruit), and a combination of erythromycin and sulfisoxazole (strawberry-banana). SETTING: Outpatient setting. SUBJECTS: A volunteer sample of 50 healthy children (mean +/- SD age, 6.3 +/- 1.3 years) and 20 adults. MAIN OUTCOME MEASURES: After each antibiotic test dose, subjects rated its taste on a 10-cm visual analog scale incorporating a facial hedonic scale. RESULTS: The mean +/- SD taste scores of the antibiotics as rated by the children were as follows: amoxicillin-clavulanic acid, 5.7 +/- 3.6 cm; azithromycin, 6.8 +/- 3.2 cm; clarithromycin, 3.7 +/- 3.6 cm; and erythromycin-sulfisoxazole, 4.9 +/- 3.5 cm. The mean +/- SD taste score for erythromycin-sulfisoxazole (ie, 2.7 +/- 2.3) assigned by the adults was significantly different than that given by the children (P = .01) with no difference noted for the other 3 drugs. Children and adults both selected azithromycin most often as best tasting. There was a significant difference in the proportions selecting each antibiotic as worst tasting, with the children tending to dislike clarithromycin and the adults tending to dislike erythromycin-sulfisoxazole (P = .03). CONCLUSIONS: The taste of azithromycin was rated most highly by both children and adults, who also selected this antibiotic most often as best tasting. Differences in taste-testing results between children and adults suggest that evaluation of the palatability of medications intended for use in pediatrics should be conducted in children.

Anti-Bacterial Agents↗

PubMed2000

Macrolide antibiotics for cystic fibrosis.

BACKGROUND: Cystic Fibrosis is characterised by chest infection, the antibiotic treatment of which has significantly improved the outlook for people with this condition. The unusual nature of organisms that infect the chest of individuals with cystic fibrosis has restricted antibiotic choice. In particular the bacteria, Pseudomonas aeruginosa, is resistant to nearly all antibiotics that can be taken by mouth. There is laboratory evidence and evidence from other disease processes that macrolide antibiotics, whilst not directly active against Pseudomonas aeruginosa, may have indirect actions against this bacteria. OBJECTIVES: This review aimed to test the hypotheses that macrolide antibiotics; 1) Improve clinical status compared to placebo or another antibiotic 2) do not have unacceptable adverse effects If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. In addition, Principal Investigators, known to work in the field and previous authors were contacted for unpublished or follow up data. Pharmaceutical companies, that manufacture macrolide antibiotics, were approached. SELECTION CRITERIA: Randomised controlled trials, published or unpublished, of macrolide compared to placebo, another class of antibiotic or another macrolide. Studies which compare regimes of the same macrolide at different doses will also be included. DATA COLLECTION AND ANALYSIS: No completed randomised controlled trials were identified. MAIN RESULTS: Three open studies excluded. Four ongoing randomised controlled trials were identified. No completed randomised controlled trials were identified. REVIEWER'S CONCLUSIONS: At present, there are no randomised controlled trials to evaluate the use of macrolide antibiotics for the treatment of chest infection in people with cystic fibrosis. Such trials, with clear outcome measures, are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Anti-Bacterial Agents↗

PubMed2005

Natural antimicrobial susceptibility patterns and biochemical identification of Escherichia albertii and Hafnia alvei strains.

Bangladeshi diarrheagenic Hafnia alvei-like strains have been described recently as the new species Escherichia albertii (Int J Syst Evolut Microbiol. 2003;53:807-810). The natural susceptibility of 21 E. albertii and 76 H. alvei strains to 69 antimicrobial agents was examined, applying a microdilution procedure in IsoSensitest broth (for all the strains) and cation-adjusted Mueller-Hinton broth (for some strains). Examining the phenotypic features of both taxa with commercial identification systems and conventional tests, a database for an accurate biochemical separation of E. albertii from H. alvei was also established. Both taxa were naturally sensitive or sensitive and of intermediate susceptibility to aminoglycosides, acylureidopenicillins, ticarcillin, several cephalosporins, carbapenems, aztreonam, quinolones, folate pathway inhibitors, and nitrofurantoin. They were naturally resistant to tetracycline, penicillin G, oxacillin, all macrolides except for azithromycin, lincosamides, streptogramins, glycopeptides, rifampicin, and fusidic acid. Taxon-related differences in natural susceptibility affecting clinical assessment criteria were seen with doxycycline, minocycline, aminopenicillins, some cephalosporins, azithromycin, and fosfomycin. E. albertii was more susceptible than H. alvei to these agents and was naturally sensitive to all beta-lactams (except for penicillin G and oxacillin), azithromycin, and fosfomycin. H. alvei was naturally resistant or of intermediate susceptibility to all tetracyclines, amoxicillin, amoxicillin-clavulanate, ampicillin-sulbactam, narrow-spectrum cephalosporins, azithromycin, and fosfomycin. Motile malonate-negative Hafnia strains (indicating genospecies 2 of the H. alvei complex) were less susceptible to some cephalosporins than nonmotile, malonate-positive hafniae (indicating genospecies 1). Proline deaminase, hydroxyproline amidase, tripeptidase, chitinase, Voges-Proskauer reaction, and assimilation of histidine as well as acid production from glycerol, rhamnose, and xylose were suitable tests to separate strains of E. albertii from those of the H. alvei complex. Although out of the scope of this study, it should be noted that several strains of E. albertii showed acquired resistances to some penicillins and antifolates.

Anti-Bacterial Agents↗

PubMed2006

In vitro activities of non-traditional antimicrobials alone or in combination against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii isolated from intensive care units.

The aim of this study was to assess the in vitro activity of a number of non-traditional antibiotics (colistin, azithromycin, doxycycline and rifampicin) against multidrug-resistant (MDR) strains of Pseudomonas aeruginosa and Acinetobacter baumannii isolated from Intensive Care Units (ICUs). We also used the checkerboard method to determine whether combinations of colistin with another non-traditional antibiotic or meropenem act synergistically against these strains. Thirty-five P. aeruginosa and 25 A. baumannii strains that were found to be MDR were included the study. Isolates were collected from the specimens of patients in ICUs from 2001 to 2003. All isolates were identified by standard methods and stored at -20 degrees C until use. Antibiotic powders of azithromycin, doxycycline, rifampicin, meropenem and colistin were obtained from their manufacturers. Minimum inhibitory concentrations (MICs) were determined by the agar dilution method on Mueller-Hinton agar. Five strains of A. baumannii and five strains of P. aeruginosa, all of which had different MIC values for colistin, were selected for the synergy study using the checkerboard titration method. The susceptibility results for doxycycline and meropenem were interpreted according to National Committee for Clinical Laboratory Standards guidelines. The susceptibility breakpoints for colistin and rifampicin were established as 4 mg/L and 2 mg/L, respectively, based on previous studies. Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922 were used as control strains. Testing against the P. aeruginosa strains revealed high MIC50 values for all the drugs except colistin. Doxycycline and colistin were both effective against the A. baumannii strains, with high susceptibility rates of 92% and 100%, respectively. Azithromycin had a high MIC50 value against these strains, whilst rifampicin had a moderate effect (susceptibility rate 64%). The combination of colistin and rifampicin was fully synergistic against four A. baumannii and two P. aeruginosa strains. Combinations of colistin with meropenem and of colistin with azithromycin each showed synergistic activity against three A. baumannii isolates, whilst the same combinations resulted in generally additive or indifferent effects against P. aeruginosa strains. The colistin and doxycycline combination was generally partially synergistic or additive against all the isolates. MDR strains of P. aeruginosa and A. baumannii, which cause nosocomial infections with an increasing ratio in recent years, have limited treatment options. According to our in vitro study results, non-traditional antibiotics such as doxycycline and colistin can be an alternative for the treatment of infections caused by these strains. Combinations of colistin with non-traditional antibiotics or meropenem could be promising alternatives for the treatment of infections due to MDR strains of A. baumannii and P. aeruginosa.

Acinetobacter Infections↗

PubMed2000

Antimicrobial resistance in Burkholderia pseudomallei.

Four strains of Burkholderia pseudomallei were used to determine the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves with 13 single antimicrobial agents: ceftazidime, piperacillin, imipenem, amoxicillin/clavulanic acid, doxycycline, cotrimoxazole, kanamycin, rifampicin, ciprofloxacin, trovafloxacin, clarithromycin, azithromycin and meropenem. The time-kill studies were also performed with 33 pairs of combinations of the above antimicrobial agents: 15 combinations which would be expected to be used for acute therapy and 18 combinations for maintenance therapy. The results show that the single and combination antimicrobial agents with bactericidal effects against the four strains of B. pseudomallei which should be used for clinical trials in acute melioidosis are: imipenem, meropenem, and imipenem + azithromycin. The combination antimicrobial agents which should be further studied for the ability to eliminate biofilm and intracellular killing effect are ciprofloxacin + clarithromycin, ciprofloxacin + azithromycin, and imipenem + azithromycin.

Anti-Bacterial Agents↗

PubMed2003

Activity of nine oral agents against gram-positive and gram-negative bacteria encountered in community-acquired infections: use of pharmacokinetic/pharmacodynamic breakpoints in the comparative assessment of beta-lactam and macrolide antimicrobial agents.

BACKGROUND: The application of pharmacokinetic (PK) and pharmacodynamic (PD) data in conjunction with minimum inhibitory concentrations (MICs) of antibacterial agents has been shown to allow for improved selection and appropriate dosing of antimicrobial agents for specific infections, increasing the likelihood of bacteriologic cure and, through this, reducing the risk for the development of resistant organisms. OBJECTIVES: This study was undertaken to provide data on current levels of resistance among common community-acquired bacterial species to 7 betalactam antimicrobial agents (including the combination product amoxicillin/clavulanate), azithromycin, and clarithromycin, determined through application of the PK/PD breakpoints based on time-above-MIC for the beta-lactams and the nonazalide macrolide clarithromycin, and on 24-hour serum area under the curve divided by MIC for the azalide macrolide azithromycin. METHODS: The antimicrobial products tested were amoxicillin/clavylanate, cefpodoxime, cefdinir, cefditoren, cefprozil, cefuroxime, cefixime, azithromycin, and clarithromycin. The bacterial species comprised 70 penicillin-susceptible, 68 penicillin-intermediate, and 69 penicillin-resistant strains of Streptococcus pneumoniae; 46 beta-lactamase-positive and 54 beta-lactamase-negative strains of Haemophilus influenzae; 49 strains of Moraxella catarrhalis; and 100 methicillin-sensitive strains of Staphylococcus aureus (MSSA). Strains were isolated from clinical specimens obtained from outpatient-acquired infections in 1 clinical center in the Northeast and 1 in the north-central area of the United States within the past 2 years. National Committee for Clinical Laboratory Standards microdilution MIC methodology was used. PK/PD breakpoints were obtained from previously published studies and were based on blood values. RESULTS: Amoxicillin/clavulanate was the product to which the greatest percentage of susceptible, intermediate, and resistant strains of pneumococci were sensitive at the PK/PD breakpoint, followed by cefditoren, cefpodoxime, cefuroxime, cefdinir, and cefprozil. None of the cephalosporins were active against penicillin-resistant pneumococci. Cefditoren and cefpodozime were the agents to which the greatest percentage of beta-lactamase-positive and beta-lactamase-negative strains of H influenzae were sensitive, followed by amoxicillin/clavulanate, cefdinir, and cefuroxime. Cefprozil was inactive against H influenzae. All of the beta-lactam products were active against M catarrhalis. All but cefpodoxime, cefditoren, and cefixime were active against MSSA. CONCLUSIONS: In this study, based on PK/PD breakpoints, amoxicillin/clavulanate had the best overall activity of the 9 antimicrobial products tested. Cefpodoxime and cefditoren were active against >or=90% of strains of penicillin-susceptible and penicillin-intermediate pneumococci, H influenzae, and M catarrhalis. The macrolides azithromycin and clarithromycin were active against penicillin-susceptible and penicillin-intermediate pneumococci and M catarrhalis; they were inactive against H influenzae and penicillin-resistant pneumococci.

Administration, Oral↗

PubMed2002

Antimicrobial susceptibilities of Streptococcus pyogenes isolated from respiratory and skin and soft tissue infections: United States LIBRA surveillance data from 1999.

This study evaluated current levels of antimicrobial resistance and associated demographic trends among clinical isolates of Streptococcus pyogenes in the United States as part of the LIBRA surveillance initiative. In 1999, 2,742 isolates of S. pyogenes (2,039 respiratory; 405 skin and soft tissue; 148 blood) were collected from 324 clinical laboratories and centrally tested for antimicrobial susceptibility by the broth microdilution method. All isolates were susceptible to penicillin (MIC(90,) < or = 0.06 microg/mL), ceftriaxone (MIC(90,) < or =0.03 microg/mL), vancomycin (MIC(90,) 0.5 microg/mL), levofloxacin (MIC(90,) 1 microg/mL), and moxifloxacin (MIC(90,) 0.25 microg/mL). Twenty-four (0.9%) azithromycin-intermediate (MIC, 1 microg/mL) and 170 (6.2%) azithromycin-resistant (MIC, > or = 2 microg/mL) isolates were identified. Regionally, azithromycin resistance varied by < 5%, ranging from 3.0% in New England to 7.7% in the Pacific region. Azithromycin resistance was significantly higher (P < 0.001) among patients aged 15-64 years (8.3%) than patients < or =14 years (4.3%). This study found higher rates of macrolide resistance among S. pyogenes than previously reported in the United States and suggests that macrolide resistance is common among respiratory isolates from both younger and older patients. Fluoroquinolones (moxifloxacin > levofloxacin) demonstrated potent in vitro activity against all isolates of S. pyogenes tested, including those from skin and soft tissue infections. Given the higher rates of macrolide resistance reported in other countries and the seriousness of invasive infections, continued antimicrobial surveillance of S. pyogenes in the United States would be prudent.

Adolescent↗

PubMed2002

[Diagnosis and treatment of legionella pneumonia].

Legionellosis is a relatively rare condition but nevertheless is associated more frequently than many other pathogens with a severe course. Therefore, establishing a diagnosis of Legionellosis remains a challenge. The most significant progress in the diagnosis of Legionellosis is antigen-testing in urine by a rapid immunochromatographic test (ICT). This is an easy to handle bedside test which provides a result within 15 minutes. Sensitivity and specificity reach 80 % and 100 %, respectively. However, the exact place of this test within algorithms of clinical decision making still remains unsettled. Macrolides, doxycycline, fluoroquinolones and ketolides, and possibly also streptogramins are drugs with definitely or most probably sufficient activity against Legionella spp. and, therefore, are appropriate candidates within empirical initial antimicrobial treatment regimen of community-acquired pneumonia. Macrolides and fluoroquinolones should be the drugs of choice for the treatment of established Legionellosis. Oral macrolides should be prefered in patients with mild to moderate pneumonia; within the macrolides, azithromycin has the most favourable profile of activity. Alternatively, ciprofloxacin, levofloxacin and moxifloxacin may be selected. In severe Legionellosis as well as independently of severity in nosocomial legionellosis and immunosuppressed patients, intravenous fluoroquinolones are first choice drugs. Alternatively, azithromycin may be used. Whether a combination treatment including azithromycin or fluoroquinolones with rifampin or azithromycin with fluoroquinolone exert superior activity remains currently unknown.

Anti-Bacterial Agents↗

PubMed2002

Effect of macrolide antibiotics on human endothelial cells activated by Chlamydia pneumoniae infection and tumor necrosis factor-alpha.

This study investigated the potential anti-inflammatory activity of 3 macrolide antibiotics, clarithromycin, roxithromycin, and azithromycin, in an in vitro model of transendothelial migration (TEM). Human umbilical vein endothelial cells (HUVECs) were seeded in Transwell inserts, treated with serial dilutions of the antibiotics, and infected with Chlamydia pneumoniae or stimulated with tumor necrosis factor (TNF)-alpha. In HUVECs infected with C. pneumoniae or stimulated with TNF-alpha, both azithromycin and roxithromycin caused significant decreases in neutrophil and monocyte TEM, compared with antibiotic-free controls. Clarithromycin had no detectable effect in either group. Azithromycin caused significant decreases in interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1, whereas roxithromycin significantly decreased IL-8. This study indicates heterogeneity in the anti-inflammatory activity of these antibiotics. Mechanisms of monocyte and neutrophil TEM inhibition by azithromycin and roxithromycin are unclear but may be partially due to inhibition of IL-8 and MCP-1 production.

Anti-Bacterial Agents↗

PubMed2000

Pharmacotherapy of acute sinusitis in children.

The pharmacotherapeutic options for acute sinusitis in children are reviewed. Acute sinusitis occurs more frequently in children than in adults. The diagnosis is based primarily on clinical signs and symptoms. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the organisms most frequently implicated. A variety of antimicrobials have FDA-approved labeling for use in the treatment of sinusitis. In randomized, controlled clinical trials identified in a MEDLINE search for the period from 1966 to 1999, amoxicillin had efficacy similar to that of amoxicillin-clavulanate, azithromycin, cefuroxime, and clarithromycin in treating acute sinusitis in children. Azithromycin was effective as a three-day course of treatment. Amoxicillin and cefuroxime are better tolerated than most antibiotics; azithromycin and clarithromycin are also well tolerated. Amoxicillin-clavulanate tends to cause more gastrointestinal symptoms than amoxicillin and is more expensive. Azithromycin is more expensive than amoxicillin but less expensive than other broad-spectrum antimicrobials. Amoxicillin remains the drug of first choice for treating acute sinusitis in children. It has been found to be as effective as other broad-spectrum agents, better tolerated, and less expensive.

Acute Disease↗

PubMed2000

Comparative efficacy of gemifloxacin in experimental models of pyelonephritis and wound infection.

Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), gemifloxacin reduced bacterial numbers significantly (P < 0.01) compared with no treatment. No comparator agent had a greater effect than gemifloxacin. Notably, grepafloxacin and azithromycin were significantly less effective (P < 0.01) than gemifloxacin against E. coli pyelonephritis, and amoxycillin-clavulanate, azithromycin and trovafloxacin were inferior (P < 0.01) against P. mirabilis infection. In the S. pyogenes wound infection model, gemifloxacin, amoxycillin-clavulanate, cefuroxime and azithromycin reduced bacterial numbers significantly compared with controls (P < 0.01). Results for the comparator quinolones were not significantly different from untreated controls (P > 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than gemifloxacin (P < 0.01). No comparator agent had greater activity than gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.

Animals↗

PubMed2025

Effects of commonly used antibiotics on children's developing gut microbiomes and resistomes in peri-urban Lima, Peru.

BACKGROUND: The effects of antibiotic use on children's gut microbiomes and resistomes are not well characterized in middle-income countries, where antibiotic consumption is exceptionally common. OBJECTIVES: We characterized the effects of antibiotics commonly used by Peruvian children (i.e. amoxicillin, azithromycin, cefalexin, trimethoprim/sulfamethoxazole) on the α-diversity, β-diversity and abundance of gut genera and antibiotic resistance genes (ARGs) from 3 to 16 months. METHODS: This study included 54 children from a prospective cohort of enteric infections in peri-urban Lima, 2016-19. Stools collected at 3, 6, 7, 9, 12 and 16 months underwent DNA extraction and short-read metagenomic sequencing. We profiled the taxonomy of stool metagenomes and assessed ARG abundance by aligning reads to the ResFinder database. We used daily surveillance data (40 662 observations) to tabulate the number of antibiotic courses consumed in the 30 days prior to stool sampling. Using linear mixed models, we examined associations of recent antibiotic use with richness, diversity and abundance of gut genera and ARGs over time. RESULTS: Each additional recent antibiotic course decreased Bifidobacterium and Dialister abundance and increased Veillonella abundance, although gut richness and diversity were not affected. Recent use of amoxicillin, azithromycin, cefalexin or trimethoprim/sulfamethoxazole, specifically, did not impact gut microbiome measures. Amoxicillin, azithromycin and trimethoprim/sulfamethoxazole significantly enriched multiple ARGs and amoxicillin use significantly increased total ARGs. CONCLUSIONS: Common antibiotics like amoxicillin and azithromycin appear to be key drivers of the paediatric gut resistome. Resistome perturbations appeared to be stronger, or persist for longer, than gut microbiome effects in this middle-income country setting.

Humans↗

PubMed2005

Involvement of the CmeABC efflux pump in the macrolide resistance of Campylobacter coli.

OBJECTIVES: This study was conducted to examine the role of the CmeABC efflux pump in decreasing the susceptibility of Campylobacter coli to macrolides and ketolides in the context of absence or presence of mutations in the 23S rRNA genes. METHODS: The cmeB gene was inactivated in strains of C. coli showing two different patterns of erythromycin resistance (low or high level of resistance) associated with the absence or presence of a A2075G mutation in the 23S rRNA genes. MICs of erythromycin, azithromycin, tylosin, telithromycin and ciprofloxacin were compared for wild-type (with or without efflux pump inhibitor) and mutant strains. RESULTS: The cmeB gene inactivation (or addition of efflux pump inhibitor) led to the restoration of susceptibility of the low-level-resistant strains (no A2075G mutation in the 23S rRNA genes). In the highly resistant strains (A2075G mutation in the 23S rRNA genes), the MICs of erythromycin decreased 128- to 512-fold upon inactivation of the cmeB gene. MICs of azithromycin, tylosin and telithromycin were also affected by both addition of efflux pump inhibitor and cmeB gene inactivation, revealing these molecules as substrates of the CmeABC efflux pump. Compared with azithromycin, MICs of telithromycin drastically decreased upon cmeB gene inactivation even in the presence of a A2075G mutation in 23S rRNA genes. CONCLUSIONS: The CmeABC efflux pump acts synergically with 23S rRNA mutations to drastically increase the MICs of erythromycin and tylosin in C. coli. In contrast, azithromycin was less affected by efflux and telithromycin, although being a good substrate for the CmeABC efflux pump, was less affected by an A2075G mutation in 23S rRNA genes.

ATP-Binding Cassette Transporters↗

PubMed1997

Prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS: a cost-effectiveness analysis.

OBJECTIVE: To determine the effectiveness and costs of prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with AIDS. DESIGN: A decision analysis model was constructed to compare rifabutin (300 mg/day), azithromycin (1200 mg/week), and clarithromycin (500 mg twice per day) with no prophylaxis. Sensitivity analysis was done on all model parameters, including initial CD4 count for beginning prophylaxis. SETTING: The setting was hypothetical for the cost-effectiveness model. Clinical data were taken from published prospective randomized controlled trials. MAIN OUTCOME MEASURES: Outcomes were measured in terms of projected life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness in U.S. dollars per quality-adjusted life-year saved ($/QALY). RESULTS: For patients with AIDS and those having CD4 counts <75 cells/mm3, azithromycin, clarithromycin, and rifabutin prophylaxis increased lifetime per person MAC-related costs by $994, $2,117, and $2,185 U.S., respectively. Quality-adjusted life expectancy increased from 1.6068 QALYs to between 1.6186 and 1.6255 QALYs. The cost-effectiveness ratios were $58,200, $116,000, and $179,100/QALY saved for azithromycin, clarithromycin, and rifabutin prophylaxis, respectively, each compared with no prophylaxis. Results were most dependent on the annual cost of prophylaxis, the initial CD4 count when starting prophylaxis, and any survival benefit with prophylaxis. For each type of prophylaxis, strategies beginning with CD4 counts <25 or 50 cells/mm3 were substantially more cost-effective than those beginning in patients with higher CD4 counts. CONCLUSIONS: MAC prophylaxis is likely to cost society an additional $99 to $219 million U.S. per 100,000 patients treated. In the context of Centers for Disease Control and Prevention (CDC) recommendations to use prophylaxis in patients with CD4 counts <75 cells/mm3, azithromycin represents the best value and is most cost-effective when used in patients with CD4 counts <25 cells/mm3.

AIDS-Related Opportunistic Infections↗