Quadruple Resistance Research Articles

Analysis of Helicobacter pylori resistance in patients with different gastric diseases

Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age.

Characterization of mutations conferring streptomycin resistance in \(\textit{Mycobacterium tuberculosis}\) in Vietnam

Recently, World Health Organization (WHO) has listed streptomycin (STR) in the list of second-line injectable drugs in the multidrug-resistant tuberculosis (MDR-TB) regimens and may replace amikacin under the same conditions. Nevertheless, molecular characterizations associated with STR resistance in the Mycobacterium tuberculosis population have not been fully investigated in Vietnam. The present study aimed to explore the variation and frequency of mutations in rpsL and rrs genes and their relationship with drug-resistant patterns and M. tuberculosis genotypes in 163 STR-resistant strains from Vietnam. The mutation frequency of the rpsL and rrs genes were 62% and 20.9%, respectively, and the mutation combination in both genes covered 81% of STR-resistant strains. The most prevalent mutations included rpsL Lys43Arg (38.7%), Lys88Arg (19.6%), rrs A514C (10.4%) and A517C (5.5%). Thus, sequence analysis of rpsL and rrs exhibited a sensitivity of 81% and specificity of 100% for the prediction of STR resistance in Vietnamese M. tuberculosis strains. The prevalence of STR-resistant mutations in double, triple and quadruple resistance strains was significantly different, compared with mono STR-resistant ones. Similarly, mutation frequency associated with STR resistance in MDR strains was significantly higher than that in non-MDR strains. In addition, the lineage 2 genotype was significantly correlated with a high rate of STR resistance-conferring mutation, as well as the mutation rpsL Lys43Arg (P < 0.01), while the lineage 1 genotype was associated with a low rate of STR resistance-conferring mutation and rrs mutations (P<0.05). In conclusion, sequence analysis may be useful for the rapid detection of STR resistance in MDR M. tuberculosis strains, which in turn could contribute to better control strategies of TB in Vietnam. Other molecular mechanisms associated with STR resistance in STR-resistant strains without mutations in the rpsL and rrs genes need to be further investigated.

Antibiotics Resistance Prevalence of Helicobacter pylori Strains in Northwest China.

PurposeThis study aims to estimate the resistance rate of Helicobacter pylori (HP) to commonly used antibiotics and analyze the potential influencing factors in northwest regions of China.Patients and MethodsHP-positive patients visiting the outpatient department of multiple hospitals were enrolled in the study. Then, gastric mucosal biopsy specimens were collected for HP isolation, culture, and investigation of the resistance rate of HP to amoxicillin, metronidazole, tetracycline, levofloxacin, and clarithromycin by Epsilometer test (E-test) antibiotic susceptibility testing. In addition, multi-drug resistance, the influence of HP eradication history, age, and region of residence on drug resistance rate were analyzed.ResultsIn total, 198 HP clinical strains were successfully isolated and cultured. The resistance rates of amoxicillin, metronidazole, tetracycline, levofloxacin, and clarithromycin were 16.16%, 85.86%, 7.58%, 46.46%, and 55.05%, respectively. The multi-drug resistance rates demonstrated that dual and triple resistances were 30.30% and 22.73%, respectively. The quadruple resistance rate reached 9.60%. Our results revealed that the prior eradication history of HP significantly increased levofloxacin and clarithromycin resistance. Metronidazole and levofloxacin resistances significantly differed among different age groups, which presented an upward trend with increasing age. Drug resistance rates varied with geographic regions, especially amoxicillin and clarithromycin resistance, which were highest in Hexi Corridor and Longnan regions.ConclusionThe current situation of HP resistance to common antibiotics is severe. Tetracycline is the most sensitive antibiotic, followed by amoxicillin, the first choice for HP eradication. However, the eradication failure of HP may lead to an increase in the resistance rate. Therefore, it is necessary to strengthen the standardized diagnosis and treatment of HP to improve the primary eradication rate.

Antibiotic resistance patterns of Helicobacter pylori strains isolated from the Tibet Autonomous Region, China

BackgroundThe prevalence of Helicobacter pylori antibiotic susceptibility in the Tibet Autonomous Region, China is not determined. This study aimed to evaluate the antibiotic resistance patterns of H. pylori isolates there.ResultsA total of 153 (38.5%) H. pylori strains were successfully isolated from 397 patients in People's Hospital of Tibet Autonomous Region, China. The overall resistance rates were as follows: clarithromycin (27.4%), levofloxacin (31.3%), metronidazole (86.2%), amoxicillin (15.6%), tetracycline (0%), furazolidone (0.6%), and rifampicin (73.2%). Only 2.0% of H. pylori isolates were susceptible to all tested antimicrobials, with mono resistance, dual resistance, triple resistance, quadruple resistance, and quintuple resistance being 18.3%, 44.4%, 18.3%, 12.4%, and 4.6%, respectively. The resistance rates to levofloxacin (40.5%) and amoxicillin (21.5%) in strains isolated from female patients were significantly higher than those from male patients (21.6% and 9.5%, respectively).ConclusionsThis study demonstrates high H. pylori resistance rates to clarithromycin, levofloxacin, metronidazole, and rifampicin, whereas moderate resistance to amoxicillin, and negligible resistant to tetracycline, and furazolidone in Tibet Autonomous Region, China. The high resistance to rifampicin warns further investigation of its derivative, rifabutin.

Antibiotic resistance status of helicobacter pylori strains isolatedfrom initial eradication patients in Ningbo, China, from2017 to 2021.

Resistance of Helicobacter pylori (H.pylori) to antibiotics is an evolving and dynamic process. Presence of antibiotic resistance impacts the success rate of initial eradication strategies in the clinic. To improve the success rate of initial eradication therapy and explore new antibiotic regimens, a large sample-based study utilizing antimicrobial susceptibility testing was performed. A total of 2508 H.pylori strains from patients subjected to initial eradication therapy were isolated, cultured, and tested for drug susceptibility from 2017 to 2021. The minimal inhibitory concentration (MIC) was recorded. H.pylori susceptibility profiles and its change trends from initial eradication patients were analyzed. The relationships between drug resistance, year of sample collection, age, and sex of patients were analyzed. The overall resistance rates were as follows: amoxicillin (9.25%), clarithromycin (38.48%), levofloxacin (42.86%), furazolidone (11.28%), doxycycline (8.56%), rifampicin (10.81%), tinidazole (74.32%), gatifloxacin (61.71%), tetracycline (0%), metronidazole (78.71%), ornidazole (97.87%), and fosfomycin (31.67%). Only 38.04% of the strains were pansusceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by those of mono resistance (29.90%), double resistance (24.96%), triple resistance (6.34%), and quadruple resistance (0.76%). Significant differences in the resistance rate and MIC were also observed in different age and sex groups. Time of collection and patient age and sex were associated with the distribution of antibiotic resistance. With the increasing resistance rate and multiple resistance of H.pylori to commonly used antibiotics, drug susceptibility testing is imperative to permit individualized therapy, and a regimen containing the combination of amoxicillin, furazolidone, tetracycline, doxycycline, or rifampicin is reasonable for initial empirical eradication therapy.

Investigation of multidrug-resistant Helicobacter pylori in pediatric patients: A Bulgarian study and literature data.

Antibiotic resistance of Helicobacter pylori strains from 106 symptomatic children was evaluated according to EUCAST breakpoints and rate of multidrug resistance (MDR) was analyzed. Overall resistance rates were amoxicillin 7.5%, metronidazole 25.5%, clarithromycin 34.0% and ciprofloxacin 14.1%. There were no significant differences in resistance rates according to patients' age (2-6 and 7-18 years) and sex. Combined resistance rate was 19.8%, including double, triple, and quadruple resistance in 13.2% (14 strains), 5.7% (6) and 0.9% (1) of the strains, respectively. MDR was found in 5.9% (5/84) of the children with gastritis and in two of the four children with celiac disease. The MDR was present in three children aged 4-6 years and in four children aged 10-17 years. The total MDR rate (6.6%) in Bulgarian children in 2012-2021 was higher than those in other studies based on EUCAST breakpoints such as those in pediatric patients in Slovenia in 2011-2014 (3.8%), Lithuania in 2013-2015 (0%) and Spain in 2014-2019 (0%), although being lower than those (20.7% in the untreated and 47.0% in the treated children) in China in 2019. In brief, it is of concern that MDR can strongly limit the choice of H. pylori therapy of one out of fifteen Bulgarian children and that overall resistance to both metronidazole and clarithromycin can hinder the treatment of 15.1% of the pediatric patients. Susceptibility-guided tailored eradication therapy of H. pylori infection should be more frequently implemented in the symptomatic children to avoid risks of both the infection itself and multiple antibiotic treatments.

Evolution of Susceptibilities of <i>Helicobacter pylori</i> Strains Circulating in Cameroon to Usual Antibiotics: A Three-year Study

This study was conducted to estimate the evolution of antimicrobial susceptibilities of <i>H. pylori</i> strains isolated in Cameroon from 2014 to 2016 in relation to sociodemographic factors and clinical outcomes. A total of 278 <i>H. pylori</i> strains were isolated from patients with gastroduodenal disorders and tested for their susceptibility to nine antibiotics using the disc diffusion method. With time, a significant decreased of resistance was observed against clarithromycin (31.11 to 3.20%, p<0.0001), erythromycin (66.69 to 9.6%, p<0.0001) and metronidazole (86.67 to 69.6%, p<0.0001). Resistance to tetracycline (0 to 2.4%) and doxycycline (0 to 1.6%) slightly increase with time. Resistance to amoxicillin (95.5 to 94.4%), ciprofloxacin (4.44 to 4%) and levofloxacin (0 to 0.8%) was relatively constant. No resistance was detected against rifampicin with the time. A significant decrease of resistance was detected against metronidazole / clarithromycin (22.22 to 1.6%, p<0.0001) and amoxicillin / clarithromycin (26.67 to 3.2%, p<0.0001). Among the tested isolates, 0.92 and 2.4% elicited triple resistance to metronidazole / tetracycline / amoxicillin in 2015 and 2016, and 0.8% quadruple resistance to metronidazole / tetracycline / clarithromycin / amoxicillin in 2016. Higher resistance rate was noticed as age increase and among female compared to men. Our data showed evolution in the antimicrobial susceptibilities of <i>H pylori</i> strains circulating in our milieu with time. This finding highlights the need of monitoring periodically <i>H. pylori</i> resistance profile to antibiotics in order to determine the adapted treatment for this infection.

Analysis of antibiotic resistance and influencing factors for Helicobacter pylori in children

Objective To investigate the antibiotic resistance of Helicobacter pylori(Hp) isolates cultured from endoscopic gastric mucosal samples and influencing factors for antibiotic resistance in children. Methods From April 2013 to February 2016, Hp cultured from mucosa samples of the gastric antrum and the body of stomach was investigated in 246 patients with 13C breath test positive examined by gastroscopy.Resistance to Amoxicillin, Clarithromycin, Metronidazole, Tetracycline was tested for Hp by using E-test.The clinical data were collected from the patients, and the relationship among age, gender, endoscopic diagnosis, histological performance, eradication number factors and antibiotic resistance rate were analyzed. Results Of 246 specimens, 174 cases (70.7%) were positive.The overall antibiotic resistance rates of isolates obtained were 96.55% (168/174 cases), 57.47% (100/174 cases), 4.02% (7/174 cases), 1.15%(2/174 cases) with respect to Clarithromycin, Metronidazole, Tetracycline and Amoxicillin.An antibiotic resistance rate was 43.10% (75/174 strains), among which the Clarithromycin resistance rate was 93.33% (70/75 strains), and the Metronidazole resistance rate was 6.67% (5/75 strains). Double resistance rate was of 54.02%(94/174 strains), among which the resistances rate of Clarithromycin+ Metronidazole was 52.30%(91/94 strains), and the resistances rate of Clarithromycin+ Tetracycline was 1.72%(3/94 strains). Triple resistance rate of Clarithromycin+ Metronidazole+ Tetracycline was 1.15%(2/174 strains). Quadruple resistance rate of Clarithromycin+ Metronidazole+ Amoxicillin+ Tetracycline was 1.15%(2/174 strains). Factor analysis showed that the resistance rate of Clarithromycin in children who had failed in eradication therapy [98.7%(148/150 cases)] was higher than that in children who had not undergone eradication therapy [83.3%(20/24 cases)], and the difference was statistically significant(χ2=14.610, P 0.05). Conclusions Hp resistance rate to Clarithromycin, Metronidazole is very high in children, but it is relatively low to Amoxicillin and Tetracycline, and multiple antibiotic resistance is at high prevalence. Key words: Helicobacter pylori; Antibiotic resistance; Child

Antibiotic resistance of Helicobacter pylori to 16 antibiotics in clinical patients.

Resistance of Helicobacter pylori (H.pylori) to antibiotics is increasing worldwide. To determine the status of H.pylori resistance and its patterns in clinical patients, an investigation utilizing susceptibility testing for commonly used antibiotics was needed. Total of 2283 H.pylori strains were collected from 2013 to 2016. The resistance and its patterns of these strains were tested by agar dilution method. The resistance rate and minimal inhibition concentration (MIC) in different gender groups were also analyzed. The overall resistance rates were as following: amoxicillin (1.58%), clarithromycin (22.73%), levofloxacin (24.75%), furazolidone (1.49%), doxycycline (9.20%), cefetamet (97.20%), ceftriaxone (49.60%), cefuroxime (25.20%), gentamicin (3.73%), azithromycin (85.60%), rifampicin (2.80%), metronidazole (92.53%), ornidazole (94.27%), tinidazole (87.20%), ciprofloxacin (43.20%), and moxifloxacin (38.53%). There were only 64.08% strains pan-susceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by mono resistance (23.17%), double resistance (11.13%), triple resistance (1.36%), and quadruple resistance (0.26%). Significant differences in the resistance rate and MIC were also observed in different gender groups. Antibiotic resistance trends of H.pylori is increasing in clinical patients. With the increasing resistance, it is imperative to individualized therapy based on the results of drug susceptibility testing.

Prospective multi-region study on primary antibiotic resistance of Helicobacter pylori strains isolated from Chinese patients

BackgroundLarge-scale multi-region studies are urgently needed to provide comprehensive and up-to-date information on the antibiotic resistance of Helicobacter pylori that is critical for selecting the most optimal eradication regimens. AimsTo determine the resistance patterns of Helicobacter pylori strains isolated from dyspeptic patients. MethodsThis is a prospective, multicentre, cross-sectional, observational study. Helicobacter pylori cultures were successful in 600 patients (never receiving eradication therapy) from Northern, Eastern, Middle, and Southern regions between 2008 and 2012. Resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin was determined by Epsilometer test. ResultsThe overall resistance rate was highest for metronidazole (403, 67.2%), followed by clarithromycin (225, 37.5%), levofloxacin (201, 33.5%), rifampicin (85, 14.2%), amoxicillin (41, 6.8%), and tetracycline (21, 3.5%). There were 16.3% isolates susceptible to all tested antibiotics, followed by mono-resistance (34.2%), double resistance (27.0%), triple resistance (16.8%), quadruple resistance (4.7%), quintuple resistance (0.7%) and sextuple resistance (0.3%). Independent factors influencing antibiotic resistance were gender (to levofloxacin), age (to levofloxacin), and endoscopic finding (to clarithromycin, metronidazole, and levofloxacin). Among the clarithromycin-resistant isolates, 75.6% and 48.0% were also resistant to metronidazole and levofloxacin, respectively. ConclusionsHelicobacter pylori resistance to commonly used antibiotics in China is a very serious issue, due to the high resistance rate and general multiple resistance.

Characteristics of embB mutations in multidrug-resistant Mycobacterium tuberculosis isolates in Henan, China

ObjectivesTo determine the association between embB mutations and drug resistance, and to further investigate the mechanism of embB mutations involved in the development of ethambutol and multidrug resistance in Mycobacterium tuberculosis.MethodsOne hundred and thirty-eight multidrug-resistant clinical M. tuberculosis isolates, including 86 ethambutol-resistant and 52 ethambutol-susceptible strains, were analysed to characterize mutations within the entire coding region of the embB gene. Moreover, a two-step genotyping was performed to identify the genetic lineage.ResultsIn total, 27 embB mutation types were detected in 19 distinct codons. Though a strong association was observed between embB mutations and ethambutol resistance, 19.2% of embB306 mutants and 11.5% of embB406 or embB497 mutants were ethambutol susceptible. Among 39 ethambutol-resistant strains without embB306 mutations, 51.3% harboured mutations at codons 406 or 497. Particularly, three pairs of isolates with identical embB mutations and genotyping features were identified with variant ethambutol susceptibility. Among 77 isoniazid, rifampicin, streptomycin and ethambutol quadruple drug-resistant isolates, 89.6% carried embB mutations and 83.1% could be identified by detecting 10 embB mutations.ConclusionsOur results suggest embB mutations alone are not sufficient for the development of full resistance to ethambutol in M. tuberculosis and mutations other than embB are also needed. Our study confirms the importance of mutations at embB406 and embB497 as hotspots, in addition to embB306, for detecting ethambutol resistance. Ten selected mutations of embB, covered by a short PCR product, can be used as candidate markers for the prediction of quadruple resistance to isoniazid, rifampicin, streptomycin and ethambutol.

Prevalence of multidrug-resistant Helicobacter pylori in Bulgaria

The aim of this study was to evaluate the presence and prevalence of multidrug antibacterial resistance in Helicobacter pylori in Bulgaria from 2005 to 2008. The resistance in 828 untreated adults, 124 treated adults and 105 untreated children was, respectively, 26.5, 50.8 and 16.2% for metronidazole; 18.4, 45.2 and 19% for clarithromycin; 1, 2.4 and 0% for amoxicillin; 4.4, 10.6 and 1.9% for tetracycline; and 9, 14.5 and 5.8% for ciprofloxacin. Triple resistance to the evaluated agents was uncommon and was detected in 1% of the untreated children, 3.5% of the untreated adults and 13.6% of the treated adults. Five H. pylori strains were resistant to amoxicillin, metronidazole and clarithromycin, two of them exhibiting quadruple resistance. Resistance to four of the five antibacterials tested was found in 0.7% of the untreated and 1.8% of the treated adults. The overall level of multidrug resistance in the treated adults (15.4%) was higher than that in the untreated adults (4.2%, P=0.0001) and the untreated children (1%, P=0.0001). The presence of multidrug H. pylori resistance in Bulgaria could be associated with many factors, among them the slightly increasing national use of macrolides, lincosamides and streptogramins and of quinolones since 2000, the significant increase in primary H. pylori clarithromycin resistance, the high tetracycline use between 1994 and 1999, and, in individual cases, the use of azithromycin-based regimens or reuse of nitroimidazoles. In conclusion, for the first time in a European country during the last 5 years, H. pylori strains harbouring a worrying quadruple antibacterial resistance were found in treated as well as in untreated patients. H. pylori susceptibility patterns have a tendency to become unpredictable and should be monitored constantly at both national and global levels.

Identification and molecular characterization of triple- and quadruple-resistant Helicobacter pylori clinical isolates in Germany

The aim of this study was to estimate the frequency of triple- and quadruple-resistant Helicobacter pylori isolated in Germany, to characterize those isolates molecular genetically and to identify risk factors for the development of multiresistance. Antimicrobial susceptibility to metronidazole, clarithromycin, amoxicillin, tetracycline, ciprofloxacin/levofloxacin and rifampicin in 1118 clinical isolates obtained between July 2006 and December 2007 was tested by the Etest method. For patients harbouring triple- or quadruple-resistant strains (n = 169), data on prior eradication therapies and underlying diseases were collected and evaluated. A select number of quadruple- and triple-resistant strains were examined for resistance-mediating mutations in their 23S rRNA, 16S rRNA, gyrA and rpoB genes, respectively. From 1118 clinical isolates, 13.4% (n = 150) showed phenotypic resistance to metronidazole, clarithromycin and quinolones and 0.9% (n = 10) to metronidazole, clarithromycin and rifampicin; one isolate exhibited resistance to clarithromycin, quinolones and rifampicin. In eight isolates (0.7%), we detected phenotypic quadruple resistance to metronidazole, clarithromycin, quinolones and rifampicin or tetracycline. Triple- and quadruple-resistant strains harboured resistance-associated mutations in their 23S rRNA, 16S rRNA, gyrA or rpoB genes and were nearly exclusively isolated from patients who had already been unsuccessfully treated on multiple occasions. We show that more than 15% of H. pylori strains isolated from routine samples in the German National Reference Centre are resistant to three or more antimicrobials and identified prior unsuccessful eradication therapies as a key factor for the development of multiresistance. Our data emphasize the need for further comprehensive surveillance studies monitoring the role of treatment regimens in antimicrobial resistance in H. pylori.

Efflux Pump Overexpression in Multiple-Antibiotic-Resistant Mutants of Bacteroides fragilis

Multidrug-resistant mutants of a wild-type Bacteroides fragilis strain (strain ADB77) and a quadruple resistance nodulation division family efflux pump deletion mutant (ADB77 Delta bmeB1 Delta bmeB3 Delta bmeB12 Delta bmeB15) were selected with antimicrobials. Ampicillin, doripenem, imipenem, levofloxacin, and metronidazole selected for mutants from both strains; cefoxitin selected for mutants from strain ADB77 only; and sodium dodecyl sulfate selected mutants from ADB77Delta bmeB1 Delta bmeB3 Delta bmeB12 Delta bmeB15 only. The mutants overexpressed one or more efflux pumps.

Differential Host Chemkine Response to Helicobacter pylori

Purpose: Helicobacter pylori infection is one of the most common infections worldwide. Although most of the cases are asymptomatic, some induce a vigorous immune response. Hp is a genetically diverse bacteria, and infection generally occurs with multiple strains. Hence, we hypothesized that some Hp strains may suppress robust host response induced by virulent strains. The gastric epithelium secretes chemokines in response to Hp infection. Strains that encode cag pathogenicity island activate transcription factor NF-κB, resulting in induction of IL-8 gene expression. The objectives of this study was to determine whether strain SS1, a weak inducer of host chemokine response had a suppressive effect on more virulent clinical strains. Methods: 489 patients in Chennai, South India were screened by endoscopy. Multiple gastric biopsies were obtained for rapid urease test, histopathology and culturing Hp. CagA and VacA (s1/s2, m1/m2) status were determined by RT-PCR. For Hp-mediated host chemokine response, IL-8 mRNA expression was determined in AGS cells, a human gastric epithelial cell line by Real Time RT-PCR. For NF-κB activation, EMSA assays were performed with nuclear extracts. Results: Rapid urease test was positive in 205 patients, of which 110 had positive cultures for Hp. While 89% of the isolates were resistant to metronidazole, only 11% were resistant to both metronidazole and clarithromycin, and <1% had quadruple resistance to metronidazole, amoxycillin, clarithromycin and ciprofloxacin. We next determined the status of Cag A and VacA by PCR. 35/43 of strains encoded CagA, 35/43 strains were vacAs1, and 38/43 were m1. To determine host IL-8 response, we chose two of these strains (CH1 and CH8), both being CagA+, VacAs1m1. AGS cells were either infected with strains CH1, CH8, and SS1 (CagA+, VacAs2m2), individually or together. Both, CH1 and CH8 robustly induced, while SS1 only modestly induced IL-8 mRNA expression. Furthermore, SS1 significantly suppressed the CH1- or CH8-mediated induction of IL-8 expression. Moreover, SS1 inhibited the CH1- and CH-8-mediated activation of NF-κB. Conclusions: The ability of strain SS1 to suppress the vigorous IL-8 induction mediated by the other strains suggests that a critical balance in strain-specific infection may determine the degree of chemokine response from the grastric epithelium.

Antibiotic Resistance of Shigella in Monrovia

Twenty Shigella strains were isolated from bloody stools, of which 10 had been collected from children. Eighty per cent of the Shigella isolates were serogrouped as S. flexneri. All 20 Shigella strains were susceptible to gentamicin, nalidixic acid and ciprofloxacin. More than 80% were resistant to ampicillin, cotrimoxazole and tetracycline and 65% were resistant to chloramphenicol. Ten of 20 Shigella isolates showed a quadruple resistance to all four antibiotics. The usefulness of nalidixic acid for the treatment of multiresistant Shigella infections is discussed.

The patterns and transmissibility of antibiotic resistance among clinical strains of Pseudomonas aeruginosa.

Four hundred and ninety-eight predominantly pyocin-type 10 clinical strains of Pseudomonas aeruginosa were analyzed for resistance to carbenicillin, cefoperazone, cefotaxime, ceftazidime, gentamicin, amikacin and netilmicin. Based on NCCLS-recommended MIC breakpoints, 245 strains were found to be resistant, of which 41.6% were resistant to carbenicillin, 38% to gentamicin, 37.8% to netilmicin, 26.3% to cefoperazone, 17.9% to cefotaxime, 0.6% to amikacin and none to ceftazidime. Quadruple resistance to carbenicillin, cefoperazone, gentamicin and netilmicin was the most frequent pattern observed. Resistance to older antibiotics (kanamycin, streptomycin and tetracycline) and to mercuric chloride were also common. Conjugation experiments suggested that self-transmissible and non-transmissible plasmids occurred in at least 66 strains.

Conjugal transferability of multiple resistance in Shigella strains.

Shigella strains isolated in Japan between 1971 and 1979 were surveyed for drug resistance and distribution of R plasmids. Of 2,510 strains, 89.3% were resistant to either one or various combinations of four drugs, tetracycline, chloramphenicol, streptomycin, and sulfanilamide. About 66% of the Shigella isolates were quadruply resistant. The frequency of isolation of R plasmids from quadruply resistant Shigella strains was the highest when compared with other strains resistant to various combinations of the four drugs. The conjugal transferability of 204 quadruply resistant strains isolated between 1977 and 1979 was tested by various mixed-culture methods. Among the total strains examined, 70.6% carried transferable resistance when tested by the conventional broth culture method, 90.2% transferred their resistance when, in addition the replica-plating method was used and 97.5% could transfer their resistance when the membrane filter method was also used. Although the remaining five strains could not transfer their resistance by any of the mixed culture methods, the drug resistance of four of the five strains was mobilized by the concomitant presence of F-tet or T-kan plasmid. These results indicate that almost all of the quadruple resistance in Shigella isolates was mediated by plasmid.

Studies on the cross-resistance of Mycobacterium tuberculosis, strain H37Rv, to aminoglycoside- and peptide-antibiotics.

Various phenotypes of the resistance to aminoglycoside- and peptide-antibodies of Mycobacterium tuberculosis strain H37Rv were produced by single- and/or two-step selection of the parent strain. Mutants obtained by single-step selection with antibiotics were classified into ten phenotypes; one of single resistance, two of triple resistance, three of quadruple resistance, and four of sextuple resistance. There were two kinds of sextuple resistance (high resistance to enviomycin, viomycin, capreomycin, kanamycin, lividomycin). One was isolated from the parent strain by single-step selection and could be eliminated by mutation to isoniazid resistance, the other was obtained by two-step selections and was not eliminated by mutation to isoniazid resistance. Interaction between mutation to streptomycin resistance and mutation to quadruple resistance (4R phenotype) was observed. Streptomycin resistance interfered with the formation of the 4R phenotype and produced a different phenotype, KR instead of the 4R phenotype. The existence of mutation of the 4R phenotype did not usually interfere with mutation to streptomycin resistance, but a small portion of the mutants with the 4R phenotype were altered in their phenotype from 4R to KR after addition of the mutation to streptomycin resistance. This effect of the mutation to streptomycin resistance was not observed in mutants which already had a mutation to klR phenotype (mutation to low concentrations of kanamycin only).

Drug Resistance and Distribution of R Factors in Salmonella Strains

Drug resistance and the distribution of R factors in Salmonella strains were surveyed using 1,980 strains isolated in Japan from 1955 to 1973. Resistances were mostly restricted to sulfanilamide (SA), tetracycline (TC), and streptomycin (SM), and combinations thereof. The demonstrated frequency of strains resistant to chloramphenicol (CM) was very low as compared with that in Escherichia coli and Shigella strains. In relation to resistance to TC, CM, SM and SA, the frequency of isolation of single resistance was the highest, followed by triple, double, and quadruple resistance in that order. Low frequency of isolation of quadruple resistance was due to the low frequency of CM resistance in Salmonella strains and differed from the E. coli or Shigella group. R factors with single TC resistance was most common, followed by those with TC,SM,SA; SM,SA; TC,CM,SM,SA; and single (SM and SA) resistance, in that order. Kanamycin and ampicillin resistance was unusual and mostly transmissible.