Int J Clin Pharmacol Ther. 1999 Jul;37(7):361-4.
Determination of azithromycin [Zithromax] in gastric biopsy samples.

Krichhoff RM, Laufen H, Schacke G, Kirchhoff G, Gallo E.

Institut fur Begutachtungs-, Arbeits- und Sozialmedizin IBAS, Munchen, Germany.

OBJECTIVES: To measure the concentration of azithromycin [Zithromax] in gastric biopsy samples of gastritis patients undergoing Heliobacter pylori eradication treatment with azithromycin [Zithromax] as one antibiotic constituent of the medication. PATIENTS: Seven male outpatients, non-smokers, non-alcoholics, aged 25-40 years (mean 32 years), suffering from gastritis with involvement of H. pylori. METHODS: The patients received a 5-day treatment with azithromycin [Zithromax] (1 x 500 mg on day 1 and 1 x 250 mg on days 2-5), 40 mg pantoprazole once daily and 2 x 400 mg metronidazole once daily. Samples of gastric tissue were obtained from 5 patients and of gastric juice from 2 patients, at the occasion of gastroscopic interventions. The gastric samples were subject to analysis of azithromycin, using a highly sensitive and specific HPLC method with electrochemical detection. RESULTS: The median concentrations of azithromycin [Zithromax] in gastric tissue amounted to 7.5 microg/g on day 2 and to 9.7 microg/g on day 5 of the treatment. Four days after the end of treatment, median concentrations were still at 3.9 microg/g. In all tissue samples, azithromycin [Zithromax] concentrations were well above the MIC for H. pylori (0.25 microg/ml). The well-known tissue affinity of azithromycin [Zithromax] was underlined by the lack of detectable levels in gastricjuice. CONCLUSION: The high concentrations of azithromycin [Zithromax] observed in gastric tissue of patients with gastritis on a 5-day dosage regimen point to a favorable pharmacokinetic basis for a role of azithromycin [Zithromax] as a component of the eradication therapy of Heliobacter pylori.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10442511&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 2003 May;51(5):1167-73. Epub 2003 Apr 14.
Influence of P-glycoprotein and MRP efflux pump inhibitors on the intracellular activity of azithromycin [Zithromax] and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus.

Seral C, Carryn S, Tulkens PM, Van Bambeke F.

Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de Louvain, UCL 73.70 Avenue E. Mounier 73, B-1200 Brussels, Belgium.

Antibiotic efflux pumps expressed in eukaryotic cells can decrease the intracellular accumulation of the corresponding drugs and therefore impair their activity against intracellular bacteria. We have investigated whether verapamil (an inhibitor of P-glycoprotein) and gemfibrozil (an inhibitor of multidrug resistance proteins (MRP) and other organic anion transporters), can modulate the intracellular activity of azithromycin [Zithromax] and ciprofloxacin against Listeria monocytogenes and Staphylococcus aureus in J774 macrophages. In parallel, we have measured the cell accumulation and subcellular distribution of both drugs. Antibiotics were used at equipotent extracellular concentrations (from 0.5 x to 10 x MIC) to allow for pharmacological comparisons. Azithromycin [Zithromax] was bacteriostatic against L. monocytogenes and slightly bactericidal against S. aureus. Verapamil did not improve the maximal activity of azithromycin [Zithromax] but allowed it to reach a similar effect at extracellular concentrations about seven-fold lower in both models. Azithromycin [Zithromax] was predominantly localized in cell granules (66%), the remainder being in the cytosol and in the 'nuclei/unbroken cells' fraction. Verapamil increased the cellular accumulation of azithromycin [Zithromax] by almost 2.4-fold without modifying its subcellular distribution. Ciprofloxacin displayed a strong concentration-dependent bactericidal activity in both models. Gemfibrozil increased ciprofloxacin activity almost 2.5-fold against L. monocytogenes, but not against S. aureus. Ciprofloxacin was predominantly (65%) distributed in the cytosol. Gemfibrozil increased ciprofloxacin total accumulation by approximately 2.4-fold, but the excess was only found in the cytosol. Inhibition of efflux pumps may be a useful strategy to improve antibiotic efficacy against intracellular bacteria when increased accumulation can be obtained in the compartment where bacteria sojourn.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12697643&dopt=Abstract Zithromax azithromycin

mf.uni-lj.si

OBJECTIVES: Prolongation of the corrected Q-T (Q-Tc) interval is associated with a risk of severe and even life-threatening arrythmias. It may occur as an adverse effect of various pharmacological agents including macrolides. We opted to study the influence of the azalide antibiotic azithromycin [Zithromax] on the duration of Q-Tc interval as data on this subject are limited. METHODS: A prospective study was performed on 47 patients, 31 females and 16 males, aged 19-77 (median 52) years, treated with azithromycin [Zithromax] (total dosage 3 g, divided over 5 days) for typical solitary erythema migrans. The patients were previously healthy and were not receiving any other medication. In all of them ECGs were performed before as well as 7 and 14 days after initiation of the azithromycin [Zithromax] therapy. Thus, a total of 141 ECG tracings were analyzed. Q-T intervals were measured manually in a blinded manner and corrected for heart rate according to Bazzet's formula: Q-Tc = measured Q-T (ms)/square root of R-R (s). RESULTS: Comparison of the Q-Tc intervals before, 7 days, and 14 days after the initiation of azithromycin [Zithromax] treatment revealed a mild, but not significant prolongation (median values 406, 412.5 and 419 ms with ranges of 339-488, 352-510, and 346-505 ms, respectively). Q-Tc intervals exceeding the upper normal value of 440 ms were found in the same proportion of patients prior to as after institution of treatment. None of the ECG tracings showed significant arrhythmias. CONCLUSION: In previously healthy persons, a modest statistically insignificant prolongation of the Q-Tc interval without clinical consequences was observed after completion of a course of 3 g of azithromycin [Zithromax] administered over a period of 5 days for solitary erythema migrans.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12708094&dopt=Abstract Zithromax azithromycin

supercables.es

The in vitro activity of the two-drug combinations of azithromycin [Zithromax] with amikacin, ceftazidime, ciprofloxacin or imipenem against five clonally unrelated strains of Acinobacter baumannii were evaluated. Synergy studies were performed by the checkerboard microtiter method. The fractional inhibitory concentration (FIC) index was calculated for each drug combination. None of the four combinations tested was antagonistic. The combination of azithromycin [Zithromax] and ceftazidime was synergistic (FIC index <or=0.5) for one strain and partially synergistic (FIC index 0.75) for another strain. An additive effect (FIC index = 1) was observed for the combinations of azithromycin [Zithromax] with imipenem (two strains) or ceftazidime (one strain). The activities of the other combinations were indifferent (FIC index range from 1.5 to 2.5). It is concluded that azithromycin [Zithromax] combined with ceftazidime has moderate synergistic activity against some multiresistant A. baumannii. Copyright 2003 S. Karger AG, Basel

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12714805&dopt=Abstract Zithromax azithromycin




Int J Antimicrob Agents. 2003 May;21(5):414-9.
Mutations causing in vitro resistance to azithromycin [Zithromax] in Neisseria gonorrhoeae.

Johnson SR, Sandul AL, Parekh M, Wang SA, Knapp JS, Trees DL.

Gonorrhea Research Branch, Division of AIDS, STD and TB Laboratory Research, NCID, Mailstop C-13, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.

In 1999, a cluster of gonococcal isolates exhibiting high Minimal Inhibitory Concentrations (MICs), to azithromycin [Zithromax] (2.0-4.0 mg/l) were identified in Kansas City, MO. Isolates were characterized by auxotype/serovar class, lipoprotein (Lip) subtyping and sequencing of the mtrR gene, which has been implicated in decreased azithromycin [Zithromax] susceptibility in the gonococcus. Isolates were Pro/IB-3 and contained the 17c Lip subtype. Molecular characterization of the mtrR gene revealed a 153 base pair insertion sequence located between the mtrR/mtrC promoter and the mtrC gene. Some isolates also contained a frame shift within the mtrR gene. Transformation of these mutations into an azithromycin-sensitive recipient strain resulted in transformants with MICs as high as 2.0 mg/l and inactivation of the mtrD gene reduced azithromycin [Zithromax] MICs 270-fold. These results demonstrated that the mtr mutations were responsible for the increased MICs in these isolates.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12727073&dopt=Abstract Zithromax azithromycin

emirates.net.ae

Four children on chemotherapy for acute lymphoblastic leukemia presented with severe diarrhea and dehydration. Cryptosporidium was identified in the stools using modified Ziehl-Neelsen stain. Two of them received paromomycin and responded well. One was started on paromomycin for 10 days and although there was clinical improvement, his stools examination continued to be positive for Cryptosporidium. He then received azithromycin [Zithromax] for 10 days. He responded well and his stools became negative for Cryptosporidium. The fourth patient received azithromycin [Zithromax] from the start and responded well. Cryptosporidium should be considered in all immunocompromised children with severe or prolonged diarrhea, and since it is not seen in a routine ova and parasite examination, the laboratory should be notified for diagnostic confirmation using modified Ziehl-Neelsen stain. Immunocompromised children with Cryptosporidium diarrhea may benefit from paromomycin or azithromycin [Zithromax] therapy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12729299&dopt=Abstract Zithromax azithromycin

jhsph.edu

OBJECTIVE: Household willingness to pay for treatment provides important information for programme planning. We tested for relationships between socioeconomic status, risk of trachoma, perceptions of the effects of azithromycin, and the household willingness to pay for future mass treatment with azithromycin. METHODS: We surveyed 394 households in 6 villages located in central United Republic of Tanzania regarding their willingness to pay for future azithromycin [Zithromax] treatment. A random sample of households with children under 8 years of age was selected and interviewed following an initial treatment programme in each village. Data were gathered on risk factors for trachoma, socioeconomic status, and the perceived effect of the initial azithromycin [Zithromax] treatment. Ordered probit regression analysis was used to test for statistically significant relationships. FINDINGS: 38% of responding households stated that they would not be willing to pay anything for future azithromycin [Zithromax] treatment, although they would be willing to participate in the treatment. A proxy for cash availability was positively associated with household willingness to pay for future antibiotic treatment. Cattle ownership (a risk factor) and being a household headed by a female not in a polygamous marriage (lower socioeconomic status) were associated with a lower willingness to pay for future treatment. A perceived benefit from the initial treatment was marginally associated with a willingness to pay a higher amount. CONCLUSIONS: As those at greatest risk of active trachoma indicated the lowest willingness to pay, imposing a cost recovery fee for azithromycin [Zithromax] treatment would likely reduce coverage and could prevent control of the disease at the community level.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12751418&dopt=Abstract Zithromax azithromycin