In vitro activity of the new quinolone lomefloxacin against Mycobacterium tuberculosis.

Minimal inhibitory concentrations (MIC) of ciprofloxacin, ofloxacin and lomefloxacin were determined for 90 Mycobacterium tuberculosis strains isolated from both AIDS and other patients. Eleven (12.2%) of these strains showed in vitro resistance to one or more first-line antituberculosis drugs. Susceptibility tests were done in 7H12 broth by the radiometric method. The MIC range for ciprofloxacin was 0.125 to 4.0 micrograms/ml; for ofloxacin, 0.25 to 4.0; and for lomefloxacin 0.5 to 4.0 micrograms/ml. On the basis of our data, we believe that the following MIC, when determined in 7H12 broth radiometrically, should be used as break points to classify the strain as susceptible: ciprofloxacin and ofloxacin, 1 microgram/ml or less; lomefloxacin, 2 micrograms/ml or less. Lomefloxacin on a once-daily basis deserves further evaluation as a potential supplementary drug for the treatment of tuberculosis.     

Minimal inhibitory concentrations of isoniazid, rifampin, ethambutol, and streptomycin against Mycobacterium tuberculosis strains isolated before treatment of patients in Taiwan

Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and streptomycin (SM) for susceptible "wild" M. tuberculosis strains isolated from Taiwanese patients were within the limits previously reported for strains isolated in the United States. The highest agar-determined MICs (in 7H10 and 7H11 agar) corresponded well with the critical concentrations established for these media. The highest MICs found radiometrically in 7H12 broth were significantly lower than the critical concentrations proposed for this medium. On the basis of an evaluation of the highest broth-determined MICs found in this and in the previous study (1), we suggest that the following MICs, when determined radiometrically, should be used as breakpoints to classify the strain as "susceptible": for INH, 0.1 microgram/ml or less; for RMP, 0.5 microgram/ml or less; for EMB, 4.0 micrograms/ml or less; for SM, 2.0 micrograms/ml or less.     

Effects of isoniazid and of ceforanide against virulent tubercle bacilli in cultured human macrophages

Isoniazid (INH) is said to inhibit tubercle bacilli equally well in vivo and in vitro, and to be mycobactericidal. Ceforanide (CEF) can inhibit tubercle bacilli in vitro but has been found ineffective clinically. These two drugs were tested against virulent tubercle bacilli in cultured human macrophages (MP), partly to compare the results with clinical experience, and partly for a better understanding of antituberculosis activities of these drugs in human beings. INH had the same minimal inhibitory concentration (MIC) against tubercle bacilli in MP as in 7H9 broth cultures. It killed multiplying bacilli in MP but not nonmultiplying bacilli, even at 100 times MIC. It killed both multiplying and nonmultiplying bacilli in broth cultures. It interfered with its own effectiveness against intra-MP bacilli by preventing nonmultiplying bacilli from beginning to multiply and thus become susceptible to killing. These findings help explain why this demonstrably mycobactericidal drug produces relapses of tuberculosis when used alone. It was confirmed that CEF is able to inhibit growth in broth cultures (MIC = 10 micrograms/ml). However, it was not effective against either multiplying or nonmultiplying bacilli in MP at concentrations up to 50 micrograms/ml. These results with the drugs INH and CEF support the good record of correlation between the human MP model of tuberculosis and clinical experience in antituberculosis chemotherapy.     

Rapid radiometric susceptibility testing of Mycobacterium tuberculosis.

A 48-hour radiometric test for determining the drug susceptibility of Mycobacterium tuberculosis has been developed. The test is based on the measurement of 14CO2 produced by the oxidation of formate labeled with carbon-14. The test system uses 5 X 10(7) organisms in 1 ml of Middlebrook 7H9 medium plus albumin-dextrose-catalase enrichment and 1 muCi of [14C]formate. The 14CO2 produced is measured in an ionization chamber at 24-, 48-, and 72-hour intervals, with and without the addition of antituberculous drugs. Isoniazid, streptomycin, rifampin, and ethambutol were each tested at 3 concentrations by the radiometric method and the reference (agar dilution) method. Six standard strains and 21 patient isolates were compared by both methods. Production of 14CO2 was quantitatively decreased in the presence of drugs that inhibit the organism. The radiometric method requires 2 days; the agar dilution, 14 to 21 days.     

Is pyrazinamide bactericidal against Mycobacterium tuberculosis?

Bactericidal activity of pyrazinamide (PZA) was tested at pH 5.6 in 7H12 broth against drug-susceptible M. tuberculosis strains. The highest tested concentrations of PZA, 500 and 1,000 micrograms/ml, killed no more than 76% of the bacterial population. These concentrations are more than 32 times greater than the minimal inhibitory concentration (MIC) and the achievable in vivo concentrations. Despite high clinical efficacy of PZA and its so-called sterilizing activity in mouse experiments, this drug is much less bactericidal in vitro than any other known antituberculosis drug.     

Minimal inhibitory concentrations of rifabutin, ciprofloxacin, and ofloxacin against Mycobacterium tuberculosis isolated before treatment of patients in Taiwan

Minimal inhibitory concentrations (MICs) of rifabutin, ciprofloxacin, and ofloxacin were determined for "wild" Mycobacterium tuberculosis strains, susceptible to all antituberculosis drugs in the conventional test, isolated from newly diagnosed Taiwanese patients who had never had prior treatment for tuberculosis. These MICs were within the limits previously reported for strains isolated in the United States. The range of MICs of rifabutin for Taiwanese strains was 0.015 to 0.125 micrograms/ml; ciprofloxacin, 0.25 to 2.0 micrograms/ml; ofloxacin, 0.5 to 2.0 micrograms/ml. On the basis of an evaluation of the highest broth-determined MICs found in this and in a previous study, we suggest that the following MICs, when determined in 7H12 broth radiometrically, should be used as breakpoints to classify the strain as "susceptible": for rifabutin, 0.125 micrograms/ml or less; for ofloxacin and ciprofloxacin, 2.0 micrograms/ml or less.     

Evidence that antituberculosis drugs are really effective in the treatment of pulmonary infection caused by Mycobacterium avium complex

Successful chemotherapy of pulmonary disease caused by Mycobacterium avium complex by antituberculosis drugs has been reported by a number of investigators. However, no certain evidence of the efficacy has yet been demonstrated in a controlled clinical trial. The present study has approached this problem in 2 ways: serial analysis of minimal inhibitory concentrations (MIC) during treatment and correlation of response to therapy with initial MIC. It was observed that after administration of antituberculosis drugs (rifampin, isoniazid, kanamycin, enviomycin, and minocycline), MIC values for the M. avium complex strain increased significantly. This change may be considered a result of suppression of relatively susceptible bacteria and as evidence of the efficacy of drugs. Furthermore, a correlation between the MIC values determined before chemotherapy with the conversion of sputum to negative was shown. The M. avium complex strains varied markedly in their susceptibility to antituberculosis drugs, and these susceptibilities were correlated with the chemotherapeutic effect. The fate of patients seemed to be greatly influenced by the susceptibilities of the strains that caused infection.     

Rifabutine: minimal inhibitory and bactericidal concentrations for Mycobacterium tuberculosis

The minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) of rifabutine (ansamycin LM427, spiropiperidyl rifamycin) against rifampin-susceptible and rifampin-resistant strains of Mycobacterium tuberculosis were determined. The MICs for 17 rifampin-susceptible strains were low, falling in a narrow range of 0.06 microgram/ml or less when determined by either the agar-dilution method (in 7H10 or 7H11 agar) or in 7H12 broth (radiometrically or by sampling and colony-forming units [CFU/ml] determination). The MICs of rifabutine for 21 rifampin-resistant strains were much higher, ranging from 0.25 to 16.0 micrograms/ml. The MBCs of rifabutine were 0.125 or 0.25 microgram/ml for rifampin-susceptible strains, and were 4.0 and 32.0 micrograms/ml for two tested rifampin-resistant strains. The MIC/MBC ratio was 1:4 for rifampin-susceptible strains.     

Blood agar for susceptibility testing of Mycobacterium tuberculosis against first-line drugs.

OBJECTIVE: To evaluate the performance of blood agar for the susceptibility testing of 50 Mycobacterium tuberculosis clinical isolates against isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). DESIGN: The activity of the drugs was determined by the proportion method on blood agar instead of Middlebrook 7H10 agar according to Clinical Laboratory Standard Institute recommendations. The final concentrations of INH, RMP, SM and EMB were 0.2 microg/ml, 1 microg/ ml, 2 microg/ml and 5 microg/ml, respectively. RESULTS: The results were compared with the radiometric proportion method as the reference, and the agreements were determined as 100% for INH and RMP, 92% for SM and 96% for EMB. The specificity, sensitivity, positive predictive value and negative predictive value were 90.4% and 97.5%, 100% and 90%, 66.6% and 90% and 100% and 97.5% for SM and EMB, respectively, while these values were 100% for INH and RMP. The results of susceptibility testing were obtained on the 14th day of incubation. CONCLUSION: According to this preliminary study, our results suggest that blood agar can be used as an alternative medium for the susceptibility testing of M. tuberculosis strains against INH, RMP, SM and EMB in resource-limited countries. However, further studies are needed before implementating the method in diagnostic laboratories.     

Comparative in vitro activity of three new quinolone antibiotics against recent clinical isolates

New orally absorbable quinolone derivatives, ciprofloxacin, norfloxacin, and ofloxacin demonstrated excellent activity in vitro against clinical isolates of Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis, Proteus sp. indole-positive, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Streptococcus pyogenes and enterococci. None of the 3 drugs was more than moderately effective against Bacteroides fragilis. Ciprofloxacin was 2-4 times more effective against most gram-negative strains than was either norfloxacin or ofloxacin, and was also the most effective against gram-positive strains, though the difference was less marked. Ciprofloxacin and ofloxacin were almost equally effective against S. aureus. Results with agar and with broth were comparable. The activities of all 3 drugs were essentially independent of inoculum size, as the MIC values increased less than one dilution step when the inoculum was increased from 10(3) to 10(6). The new quinolone derivatives would appear to be promising alternatives to injectable drugs such as the aminoglycosides and cephalosporins.     

Determination of the susceptibilities to antituberculosis agents in Mycobacterium avium-Mycobacterium intracellulare complex

The determination of the susceptibilities to antituberculosis agents in Mycobacterium avium-Mycobacterium intracellulare complex (MAI complex) is influenced by the size of inoculation used in the determination. Such influences differ greatly according to the drugs. By increasing the number of colony-forming units (CFU) of the inoculation to 10(6)-fold, minimal inhibitory concentrations (MICs) of rifampicin and cycloserine have increased only 2-to 3-fold. However, MICs of ethionamide, streptomycin, enviomycin and ethambutol have increased 4-to 9-fold. In contrast, MICs of isoniazid and sulfadimethoxine have increased 30-to 35-fold. Since the determination of MICs of isoniazid and sulfadimethoxine are so greatly influenced by the size of inoculation, the determinations of MICs of these two drugs should be carried out by use of the "actual count" method (6, 7, 9) or the proportion method (8). In the actual count method, the MIC is determined by inoculating 20-100 CFU. The determination of isoniazid susceptibility of M. tuberculosis (H37Rv) was influenced only slightly by the size of inoculation, but that of M. bovis (BCG) was influenced greatly as occurred in the determination of MAI complex strains.     

Anti-tuberculosis drug susceptibility testing of Mycobacterium bovis BCG Tokyo strain.

SETTING: The Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine is the only vaccine against tuberculosis (TB), owing to its valuable protective effects and low virulence. However, it can occasionally cause systemic infection in immunocompromised hosts. Isoniazid (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB) are known to be effective anti-tuberculosis drugs and are used for the treatment of BCG infections. Unfortunately, there are few studies of the susceptibility of BCG vaccine strains to these drugs. OBJECTIVE: To measure the minimum inhibitory concentrations (MICs) of BCG Tokyo vaccine products for anti-tuberculosis drugs and assess vaccine safety in terms of drug susceptibility. DESIGN: We measured the MIC for one seed and five product lots of BCG Tokyo strain for INH, RMP, SM and EMB using Middlebrook 7H11 agar plates. RESULTS: The MIC results for INH were 0.06 and 0.125 mg/ml for the product and seed lots, respectively. The MIC results for RMP, SM and EMB were 0.25-0.5, 0.25 and 2-4 microg/ml, respectively. CONCLUSION: Our results indicate that the BCG Tokyo strain was susceptible to the major anti-tuberculosis drugs and treatable even in cases of severe adverse events, including systemic infection.     

Evaluation of the BACTEC MGIT 960 system for drug susceptibility testing of Mycobacterium tuberculosis isolates compared with the proportion method on solid media]

The methods most widely used for susceptibility testing against anti-tuberculosis drug (AST) are the proportion method on L?wenstein-Jensen egg (L-J), Ogawa egg or Middle-brook agar media, and BACTEC TB 460 system. Recently, drug concentrations have been established for AST using the automated BACTEC MGIT 960 system (aMGIT). We have evaluated the BACTEC MGIT 960 SIRE kit for AST of Mycobacterium tuberculosis to isoniazid, rifampin, streptomycin and ethambutol. Also we compared the results with the proportion methods on Middlebrook 7H10 agar (7H10), L-J and Ogawa egg, and the manual MGIT system (mMGIT). Overall concordance rates among aMGIT and the proportion method on 7H10 or Ogawa media were 98.3% and 96.9% for 4 first-line drugs, respectively. Rates were particularly high for isoniazid and rifampin between aMGIT and 7H10 (efficiency of 100%). On the other hand, overall concordance rates among two egg media, L-J and Ogawa were 99.9%. Agreement between aMGIT and mMGIT was high for the AST to isoniazid and rifampin, but lower for the AST to ethambutol (90.9%), which relates to a lower specificity of mMGIT. The mean times to aMGIT and mMGIT results of susceptibility were 7 and 6 days, respectively, contrasted with 3 weeks in 7H10 and 4 weeks in L-J and Ogawa, indicating that both MGIT systems have the potential to consistently meet the turnaround time suggested by Centers for Disease Control and Prevention (CDC) of the United States. These results demonstrate that the fully automated BACTEC MGIT 960 SIRE system for AST is useful for rapid diagnosis of drug resistant tuberculosis.     

Antimycobacterial activities of rifamycin derivatives

The Standard Initial Chemotherapy, chemotherapeutic activity of which depends mostly on the two potent bactericidal drugs, INH and RFP, has made a remarkable progress in the treatment of tuberculosis. However, certain difficult situations still remain in the treatment of resistant diseases, mostly in retreatment cases especially resistant to INH and/or RFP, and of the patients who are not able to continue the Standard Regimens because of side effects and/or severe complications with various organ dysfunctions. It is evident that presently available antituberculosis drugs are not potent enough to deal satisfactorily with the above situations, and besides, there has been unsatisfactory chemotherapeutic efficacy against infections caused by Mycobacterium avium complex. The above matters strongly urge our effort to develop new antimycobacterial agents. In the present review, in vitro and in vivo activities of newly synthesized rifamycin derivatives (3'-hydroxy-5'-alkylpiperazinyl-benzoxazinorifamycins, KRMs) were discussed. Of a total of 158 newly synthesized compounds, five (KRM-1648, KRM-1657, KRM-1668, KRM-1674, KRM-2312) were selected due to significantly lower MICs than those of RFP against M. tuberculosis H37Rv and M. intracellulare 31F093T. The MIC90s of these compounds were 16 to 32 times lower than MIC90 of RFP against RFP-susceptible clinical isolates (20 strains) of M. tuberculosis, and 100 times or more lower than MIC90s of RFP against 20 disease-associated M. avium complex strains.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparative study between broth dilution and agar dilution technics in antibiograms for Candida]

The performance of broth dilution method and agar dilution method were compared by MIC (minimal inhibitory concentration) and MFC (minimal fungicidal concentration) from Candida strains to polyene and imizadole antifungal agents. The concordance between these methods was drug dependent. The best percent of concordance were showed when the polyenes were tested. The problems of sensitivity test for yeasts to antifungal drugs are discussed.     

国产抗结核固定剂量复合剂的药效学和药代动力学研究

目的 研究国产固定剂量复合剂的药效学和药代动力学，评价其抗结核作用及产品质量。方法 采用二倍稀释法测定最低抑菌浓度（MIC），以半数动物存活时间为指标比较药物对实验性结核病的疗效。高效液相色谱法测定健康志愿者口服同剂量国产及进口三药复方片剂（卫非特）的血药浓度，求出各组分的主要药代动力学参数及相对生物利用度，并用双单侧t检验分析药物等效性。结果 复方制剂各成分对结核分枝杆菌的MIC均低于单独应用时各自的MIC；对小鼠试验性结核病均显著优于三者相应剂量单独应用的效果，与国外相应产品卫非特比较未见显著性；国产与进口片剂的主要药代动力学参数t1/2、Cmax、AUC、tmax未见显著性差异，相对生物利用度生物等效性检验合格。结论 三药复方的抗结核作用具有协同作用；国产与进口片剂为等效制剂。     

萎蔫酸铜离子络合物、镉离子络合物的抗结核活性及对结核分枝杆菌基因表达的影响

目的 研究海洋微生物代谢产物萎蔫酸金属铜离子络合物与镉离子络合物体外抗结核活性,以及对Mtb H37Rv基因表达的影响。方法 应用纸片扩散法（Kind-Bauer,K-B法）初步鉴定萎蔫酸铜离子络合物、萎蔫酸镉离子络合物的抗结核活性,重复实验3次;绝对浓度间接法测定萎蔫酸铜离子络合物、萎蔫酸镉离子络合物的最低抑菌浓度（minimum inhibitory concentration ,MIC）,重复实验确定更准确的MIC;Mtb cDNA芯片检测萎蔫酸铜离子络合物、萎蔫酸镉离子络合物处理Mtb组与溶剂对照处理Mtb组表达差异的基因,重复实验一次。结果 萎蔫酸铜离子络合物、萎蔫酸镉离子络合物在卡介苗（BCG）平板抑菌圈直径分别为（30.4±0.6）mm、（30.0±0.8）mm。萎蔫酸铜离子络合物抗Mtb H37Rv的MIC为10 μg/ml;对耐多药结核分枝杆菌,萎蔫酸镉离子络合物MIC为7.5 μg/ml,低于S（MIC=25 μg/ml）和RFP（MIC=25 μg/ml）;对Mtb临床分离株（0907961,耐S和EMB）,萎蔫酸铜离子络合物的MIC（10 μg/ml）低于S（S的MIC为20 μg/ml）,萎蔫酸镉离子络合物的MIC（5 μg/ml）均低于S（MIC=20 μg/ml）、EMB（MIC=6.4 μg/ml）。Mtb cDNA芯片检测发现萎蔫酸铜离子络合物处理组与溶剂对照组比较,有差异表达的基因总数为23条,其中已知功能基因有10条;萎蔫酸镉离子络合物处理组与溶剂对照组比较,有差异表达的基因总数为28条,其中已知功能基因有11条。这些存在差异的基因功能涉及核苷酸、脂质、能量、辅酶、氨基酸代谢,DNA的复制、转录、翻译、翻译后修饰以及细胞膜的生物合成等。结论 萎蔫酸铜离子络合物与萎蔫酸镉离子络合物具有较好的体外抗结核活性,尤其对部分耐药菌株的抑制作用甚至优于抗结核一线用药,可作为抗结核药物的前导化合物;运用基因芯片所探究出的差异表达的基因为进一步深入研究其抗菌作用机制提供了一定的实验依据。     

利奈唑胺对分枝杆菌体外抑菌作用的初步研究

目的 评价利奈唑胺对MTB和5种非结核分枝杆菌(NTM)的体外抑菌作用,探讨利奈唑胺与其他抗结核药物联合使用时的体外相互作用.方法 采用微孔板Alamar Blue法测定利奈唑胺对MTB临床株121株、NTM临床菌株30株及相应标准菌株的MIC,观察利奈唑胺与7种常用抗结核药物联合使用时,对H37Rv和8株MTB 临床分离株的MIC值的影响,通过计算分级抑菌浓度指数,观察利奈唑胺与其他抗结核药物联合使用时是否存在协同作用.结果 94.2%(114/121)的MTB临床分离株可被≤1 mg/L的利奈唑胺抑制生长,利奈唑胺对敏感和MDR菌株及其他形式的耐药菌株的MIC差异无统计学意义(X2=0.481,P＞0.05).若以＞1 mg/L作为耐药标准,则5种NTM菌株中仅堪萨斯分枝杆菌对利奈唑胺敏感,脓肿分枝杆菌和偶然分枝杆菌均对利奈唑胺全耐药,鸟分枝杆菌和胞内分枝杆菌对利奈唑胺部分敏感.利奈唑胺与7种抗结核药物在体外联合使用时未表现出相关性.结论 利奈唑胺有很好的抗MTB活性,且与细菌对其他药物是否耐药无关.利奈唑胺对堪萨斯分枝杆菌有很好的抗菌活性,与其他常用抗结核药物联合使用时未表现出相关性.

Abstract：

Objective To evaluate the mycobactericidal efficacy of linezolid to Mycobacterium tuberculosis bacilli and Non-tuberculous mycobacteria ( NTM ) in vitro, and to analyze the interaction between linezolid and other anti-TB drugs in vitro.Methods The minimum inhibition concentrations (MICs) of 121 Mycobacterium tuberculosis clinical isolates and 30 non tuberculousis Mycobacteria isolates and the corresponding standard strains to linezolid were tested by Microplate Alamar Blue assay (MABA).The interactions between linezolid and rifampicin, isoniazid, streptomycin, ethambutol, kanamycin, ofloxacin,and rifabutin were also tested in vitro by fractional inhibitory concentration index ( FICI ) method.Results 94.2% ( 114/121 ) of the Mycobacterium tuberculosis isolates were inhibited by linezolid at concentrations ≤1 mg/L.There was no statistical difference in the MIC values of sensitive strains, MDR strains, and drug resistant strains other than MDR ( x2 = 0.481, P ＞0.05 ).Only Mycobacterium kansasii was totally sensitive to linezolid among the 5 tested NTM strains.In vitro drug combination testing displayed overall non-association between linezolid and 7 other anti-TB drugs among 8 clinical isolates and H37 Ry.Conclusions Linezolid showed great mycobactericidal efficacy to Mycobacterium tuberculosis clinical isolates in vitro,regardless of the strains' drug resistant parameters.This study also showed non-association of the interactions between linezolid and 7 other anti-TB drugs in vitro.     

In vitro and in vivo synergistic effect of isoniazid with streptomycin and clofazimine against Mycobacterium avium complex (MAC)

Setting: Isoniazid (INH), the powerful antituberculosis drug, has also been used in regimens for treating disease caused by Mycobacterium avium complex (MAC), an important opportunistic pathogen encountered in AIDS patients. Its use for treatment of MAC disease has also been endorsed by the American Thoracic Society. However some controversy has emerged recently in medical literature, discounting its role and even implying that its use is contraindicated in chemotherapy of MAC disease.Objective: In view of the controversy, we investigated its in vitro and in vivo activity in combination with streptomycin (SM) and clofazimine (CFM) against MAC.Design: In the in vitro studies, the minimal inhibitory concentrations (MIC) of individual drugs or combinations of INH and SM as well as INH and CFM were determined in a checker-board type study by both conventional and radiometric (BACTEC) methods. In vivo studies assessed the efficacy of chemotherapy with INH alone or in combination with either SM or CFM against MAC infection in beige mice.Results and conclusions: While MICs of INH and SM were 12.5 μg/ml and 6.25 μg/ml respectively, complete inhibition of growth was seen at 1.56 μg/ml with the combination of both drugs. The synergistic effect was observed both in conventional and BACTEC methods. In vivo studies demonstrated elevated activity when INH was given along with SM or CFM. Based on these observations we stress that isoniazid has still a place in chemotherapy of MAC disease, at least until other potent drugs are discovered.     

Inhibitory effects of aspirin and indometacin on the growth of Helicobacter pylori in vitro

OBJECTIVE: The interactions between non‐steroidal anti‐inflammatory drugs and Helicobacter pylori have not been sufficiently documented to date. The aim of this study was to investigate the possible effects of aspirin and indometacin on the growth of H. pylori and to determine the effects of aspirin on the susceptibility of H. pylori to some antimicrobials. METHODS: Kinetic studies were performed by inoculating strains of H. pylori in brucella broth with different concentrations of aspirin and indometacin. Growth of bacteria in the broth was assessed spectrophotometrically and by viable colony counts after incubation for 24 and 48 h. Bacterial morphology was determined by Gram stain under light microscopy. The minimal inhibitory concentration (MIC) of aspirin and indometacin was determined by the standard agar dilution method. The MIC of amoxicillin, clarithromycin and metronidazole was measured in the presence and absence of aspirin by the E‐test method. RESULTS: Kinetic studies revealed that aspirin and indometacin inhibited the growth of H. pylori in a dose‐dependent manner. The bactericidal activity of these agents was expressed by cell lysis. Aspirin at 400 µg/mL produced an almost 2‐log decrease in the number of CFU/mL at 48 h. Similar inhibitory effects were obtained when 100 µg/mL indometacin was tested. The MIC at which 90% of H. pylori was inhibited was 512 µg/mL and 128 µg/mL for aspirin and indometacin, respectively. Increased susceptibility of H. pylori to amoxicillin, clarithromycin and metro­nidazole was found in the presence of aspirin. CONCLUSIONS: Aspirin and indometacin could significantly inhibit the growth of H. pylori when incubated in brucella broth in vitro. A subinhibitory concentration of aspirin enhanced the susceptibility of H. pylori to some antimicrobial agents.