Emergence Of Quinolone Resistance Research Articles

VIBRIO CHOLERAE EL TOR ANTIBIOTIC RESISTANCE GATHERED FROM ENVIRONMENTAL OBJECTS ON THE TERRITORY OF THE RUSSIAN FEDERATION

The paper presents the analysis of Vibrio cholerae El Tor strains antibiotic resistance gathered from environmental objects on the territory of the Russian Federation during 2007–2016. We determined the sensitivity of 268 strains of V. cholerae El Tor to 12 antibacterial drugs by the method of serial dilutions in a dense nutrient medium. The strains showed resistance to 1–7 antibacterial drugs. The emergence of quinolone resistance in polyresistant strains of V. cholerae E.

Association of Salmonella Serotypes with Quinolone Resistance in Broilers.

Fluoroquinolone is widely used for the treatment of bacterial diseases, and the emergence of quinolone resistance has become a serious concern in recent years, owing to an increase and inappropriate use of antimicrobials. Here, we attempted to understand the differences in the emergence frequency of quinolone-resistant bacterial variants in three Salmonella serotypes S. Infantis, S. Schwarzengrund, and S. Manhattan—which are mainly found in broiler industries in Japan. Emergence frequency tests for quinolone-resistant variants using enrofloxacin-containing agar plates and sequence analysis in the quinolone resistance-determining region (QRDR) of gyrA in DNA gyrase were performed. The results showed no significant difference in the emergence frequency among the three serotypes, and most of the resistant variants had mutations in the QRDR region. These findings suggest that differences in the serotypes tested are not associated with the emergence frequency of quinolone-resistant variants.

New Horizons in Mycoplasma genitalium Treatment.

Mycoplasmagenitalium is an important sexually transmitted pathogen responsible for both male and female genital tract disease. Appreciation of its significance in human disease has been hampered by its slow growth in culture, difficulty in isolating it, and lack of commercial molecular-based tests for rapid detection. Comparatively few in vitro data on antimicrobial susceptibility are available due to the scarcity of clinical isolates and difficulty in performing susceptibility tests to determine minimum inhibitory concentrations for M. genitalium. Antimicrobial agents that inhibit protein synthesis such as macrolides, along with fluoroquinolones that inhibit DNA replication, have been the treatments of choice for M. genitalium infections. Even though international guidelines recommend azithromycin as first-line treatment, rapid spread of macrolide resistance as well as emergence of quinolone resistance has occurred. Increasing rates of treatment failure have resulted in an urgent need for new therapies and renewed interest in other classes such as aminocyclitols, phenicols, and streptogramins as treatment alternatives. Limited data for new investigational antimicrobials such as the ketolide solithromycin suggest that this drug may eventually prove useful in management of some resistant M. genitalium infections, although it is not likely to achieve cure rates >80% in macrolide-resistant strains, in a similar range as recently reported for pristinamycin. However, agents with completely new targets and/or mechanisms that would be less likely to show cross-resistance with currently available drugs may hold the greatest promise. Lefamulin, a pleuromutilin, and new nonquinolone topoisomerase inhibitors are attractive possibilities that require further investigation.

ANTIBIOTIC RESISTANCE OF VIBRIO CHOLERAE O1 EL TOR ISOLATED ON THE TERRITORY OF THE RUSSIAN FEDERATION IN 2006-2015

Aim of the study. The analysis of antibiotic resistance and molecular mechanisms of the persistence of Vibrio cholerae О1 El Tor strains, isolated from patients and environmental objects on the territory of the Russian Federation in 2006-2015. Material and Methods. The susceptibility of 34 V. cholerae El Tor strains to 13 antibacterial drugs was determined by the method of serial dilutions in a rich culture medium (Instructional Guidelines (МUК) 4.2.2495-09). Results. The strains showed resistance to 1-5 antibiotics (levomicetin, streptomycin, nalidixic acid, furazolidone, trimethoprim/sulfamethoxazole) and harbored SXT-element with antibiotic resistance genes. The emergence of quinolone resistance in V. cholerae O1 El Tor strains with accompanying multiple drug resistance limits the choice for drugs for etiotropic therapy and aggravates the possibility of unfavourable cholera outcome.

Emergence of Quinolone Resistance and Re-Emergence of Susceptibility to First Line Antibiotics in Salmonella Spp. Isolated in a Tertiary Care Hospital

Emergence of Quinolone Resistance and Re-Emergence of Susceptibility to First Line Antibiotics in Salmonella Spp. Isolated in a Tertiary Care Hospital

Quinolone Resistance among Extended-Spectrum β-Lactamases Producing Klebsiella Pneumoniae in Sohag University Hospital, Upper Egypt

Background: Extended-spectrum β-lactamases (ESBLs) production is the major resistance mechanism to β-lactam antibiotics in Enterobacteriaceae. Moreover, the emergence of quinolone resistance in ESBLs-producing isolates had become a global threat for treatment of infections caused by these bacteria. Objectives: We investigated the association between ESBLs production and quinolone resistance in Klebsiella pneumoniae isolates. Methodology: A total of 148 isolates of K. pneumoniae collected from Sohag University Hospital over the period of 10 months between June 2014 and April 2015. Identification of Klebsiella pneumoniae was performed with the Vitek 2 system (bioMerieux, France). Screening for extended spectrum beta lactamases (ESBLs) production was done with the Vitek 2 system (bioMerieux, France) and confirmed using the combined disk diffusion test (CDDT) .The ESBL’s genotype was then analyzed by multiplex PCR of bla TEM , bla SHV and bla CTX-M genes. Also multiplex PCR was used for detection of quinolone resistance determinant genes qnrA, qnrB and qnrS among ESBLs-producing K. pneumonia isolates. Results : In our study we found that among the 148 K. pneumoniae isolates; 121 (81.7%) were ESBLs producers according to CDDT results, bla TEM was found in 44% of them, while bla CTX-M found in 6%, bla TEM and bla CTX-M together found in 39% of the isolates, but in 7% bla TEM , bla SHV were found together, the three genes bla TEM , bla SHV and bla CTX-M were found in 4% but none of the isolates carried bla SHV gene alone or with bla CTX-M . 113(93%) of the 121 ESBLs producing isolates were found to carry one or more of quinolone resistance (QNR) genes qnrA, qnrB, qnrS. The three genes together were found in (53.9%) of the isolates, while qnrS was found in (29.1%), qnrA in (11%) of the isolates and (6%) carried both qnr B and S. Conclusions: Our results showed coexistence of ESBLs production and quinolone resistance in the majority of the K. pneumoniae isolates suggesting that more care should be taken for the choice of antibiotic therapy beside strict application of infection control policies to prevent dissemination of the multidrug resistant strains.

Emergence of quinolone resistance in the microbiota of hospitalized patients treated or not with a fluoroquinolone.

Quinolone resistance is a major global clinical problem. It primarily emerges in microbiota under selective pressure. Studies evaluating the incidence and risk factors for carrying quinolone-resistant bacteria in hospitalized patients treated with fluoroquinolones (FQs) are lacking. We prospectively included hospitalized patients treated with FQs. Nasal, throat and rectal swabs were performed before FQ treatment, at the end of FQ treatment and 30 days later. A 'reference group' of patients not receiving FQs was also included to determine the rates of quinolone resistance acquisition not linked to FQ treatment. Prevalence and incidence of quinolone-resistant strains of nasal coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, pharyngeal α-haemolytic streptococci and faecal Escherichia coli, and risk factors for emergence of quinolone resistance in FQ-treated patients were assessed. Four-hundred and fifty-one FQ-treated patients were included, as well as 119 subjects in the 'reference group'. Emergence of quinolone resistance occurred in 110/213 (51.6%), 50/336 (14.9%), 53/290 (18.3%) and 46/336 (13.7%) of FQ-treated patients for CoNS, S. aureus, α-haemolytic streptococci and E. coli, respectively, significantly more than for reference patients for CoNS (23/65; P < 0.05), S. aureus (5/91; P < 0.02) and E. coli (4/84; P < 0.05), but not for α-haemolytic streptococci (15/70; P = 0.55). Emergence of resistance was not associated with the type of FQ received, the duration of therapy or the duration of hospital stay, but was associated with host factors such as immunosuppression and altered performance status. FQs received during hospitalization account for high rates of emergence of resistance to FQs in clinically relevant bacteria from human microbiota, reflecting the important ecological impact of FQs. Host factors outweighed treatment or hospitalization characteristics as risk factors for carrying quinolone-resistant strains.

Emergence of quinolone resistance in Salmonella and Shigella strains isolated from diarrhoea in Senegal.

B. Sambe-Ba **, A. Seck , L.G. Timbine , A.A. Wane , A. Gassama-Sow * Unite de Bacteriologie Experimentale, Institut Pasteur de Dakar, 36 avenue Pasteur, BP 220 Dakar, Senegal b Laboratoire de Biologie Medicale, Institut Pasteur de Dakar, 36 avenue Pasteur, BP 220 Dakar, Senegal Unite de Bacteriologie Experimentale, Institut Pasteur de Dakar, 36 avenue Pasteur, BP 220 Dakar, Senegal

Intracellular concentrations of enrofloxacin in quinolone-resistant Salmonella enterica subspecies enterica serovar Choleraesuis

The emergence of fluoroquinolone-resistant strains of Salmonella enterica subspecies enterica serovar Choleraesuis is an important concern in several countries, including Japan. We examined the intracellular concentration of enrofloxacin in S. Choleraesuis to determine the existence of a relationship with the emergence of quinolone resistance. The intracellular concentration of enrofloxacin was significantly lower in nalidixic acid-resistant isolates compared with nalidixic acid-susceptible isolates. In the presence of carbonyl cyanide m-chlorophenylhydrazone, the intracellular concentration of enrofloxacin increased in all isolates, with no significant difference in the intracellular concentration between nalidixic acid-susceptible and -resistant isolates. The frequency of emergence of fluoroquinolone-resistant mutants was higher in susceptible isolates with a low intracellular concentration of enrofloxacin. The results presented suggest that a decrease in the intracellular concentration of enrofloxacin is related to active efflux pumps and contributes to the emergence of fluoroquinolone resistance.

Trends in the rates of resistance ofUreaplasma urealyticumto antibiotics and identification of the mutation site in the quinolone resistance-determining region in Chinese patients

The resistance of Ureaplasma urealyticum to antibacterials, isolated from 804 patients from the outpatient clinic of the Sir Run Run Shaw Hospital Hangzhou, China, from March to June over six consecutive years (1999-2004) was reviewed. The quinolone resistance-determining region of six strains of U. urealyticum was analyzed. The level of resistance to doxycycline, josamycin, tetracycline, azithromycin, clarithromycin and pristinamycin was below 20% and did not change during the study period. The rate of resistance to fluoroquinolones (ofloxacin, ciprofloxacin) was much greater than these (>50%) and has increased since 1999. The rate of resistance to Erythromycin decreased from 63.9% in 1999 to about 20% from 2000 onwards. The widespread use of fluoroquinolones had led to high resistance rates in U. urealyticum and the emergence of quinolone resistance. Analysis of the gene sequence of topoisomerase IV and DNA gyrase suggested a role for the topoisomerase IV ParE subunit in fluoroquinolone-resistant U. urealyticum.

Quinolones for brucellosis: treating old diseases with new drugs

Although quinolones are theoretically interesting candidates for the treatment of brucellosis, the existing data concerning their efficacy are limited and conflicting. A number of small clinical studies with combination regimens that include quinolones have shown adequacy, but not superiority, although cost-effectiveness, excluding certain disease complications, is an important issue. The emergence of quinolone resistance and its implications is another drawback. Experimental data have yielded contradictory results, although most studies do not indicate a bactericidal effect for quinolones. However, in-vitro studies contrast repeatedly with the clinical response, both in terms of clinical failure, despite in-vitro success, and vice versa.

Genetic Diversity and Quinolone Resistance in Campylobacter jejuni Isolates from Poultry in Senegal

We used the multilocus sequence typing (MLST) method to evaluate the genetic diversity of 46 Campylobacter jejuni isolates from chickens and to determine the link between quinolone resistance and sequence type (ST). There were a total of 16 ST genotypes, and the majority of them belonged to seven clonal complexes previously identified by using isolates from human disease. The ST-353 complex was the most common complex, whereas the ST-21, ST-42, ST-52, and ST-257 complexes were less well represented. The resistance phenotype varied for each ST, and the Thr-86-Ile substitution in the GyrA protein was the predominant mechanism of resistance to quinolone. Nine of the 14 isolates having the Thr-86-Ile substitution belonged to the ST-353 complex. MLST showed that the emergence of quinolone resistance is not related to the diffusion of a unique clone and that there is no link between ST genotype and quinolone resistance. Based on silent mutations, different variants of the gyrA gene were shown to exist for the same ST. These data provide useful information for understanding the epidemiology of C. jejuni in Senegal.

Emergence of quinolone resistance among viridans group streptococci isolated from the oropharynx of neutropenic peripheral blood stem cell transplant patients receiving quinolone antimicrobial prophylaxis

In neutropenic patients receiving quinolone prophylaxis, bacteremia with viridans group streptococci resistant to quinolones is a known complication. The frequency of occurrence of quinolone-resistant organisms colonizing the oropharynx during antibacterial prophylaxis with a quinolone is not well defined. In 48 patients undergoing hematopoietic stem cell transplantation, the prevalence of quinolone resistance in viridans group streptococci colonizing the oropharynx before and during antibacterial prophylaxis with gatifloxacin or moxifloxacin (most with concomitant penicillin) was determined. For quinolone-resistant isolates, mutations in the genes gyrA and parC, which confer resistance to quinolones, were analyzed. Seventy-four isolates before and 27 isolates during quinolone use were recovered from patients' oropharynxes. The numbers of susceptible isolates recovered before versus during quinolone use were as follows: 52 (70%) versus three (11%) for ciprofloxacin, 66 (89%) versus eight (30%) for levofloxacin, 66 (89%) versus ten (37%) for gatifloxacin, and 67 (91%) versus 11 (41%) for moxifloxacin (p<0.0001). Mutations in gyrA and/or parC were detected in quinolone-resistant isolates. Quinolone-resistant viridans group streptococci are frequently found in the oropharynx of neutropenic patients after a brief (median, 8 days) exposure to gatifloxacin or moxifloxacin.

Emergence of Quinolone Resistance amongst &lt;i&gt;Escherichia coli&lt;/i&gt; strains isolated from Clinical infections in some Lagos State Hospitals, in Nigeria.

Two hundred and seventy three isolates of Escherichia coli obtained from 7 hospitals in Lagos were screened for Fluoroquinolone resistance (FQR). Rate of resistance was 22.3% showing an increase in quinolone resistance when compared with resistant rates between 1994 and 1999 which ranged from 0 – 2% then. In this study FQR E. coli was more common in patients with urinary tract infection (22.9%). ESBL enzyme production was found to be associated with most of the FQR E. coli strains. The prevalence of FQR E. colii in the faeces of healthy adults was 22.9%, 6.7% in children and 22.2% in avian. By Pulsed field gel electrophoresis (PFGE) the isolates were found to be genetically unrelated with most of the isolates having different antimicrobial resistance. Emergence of FQR E. coli in our environment could be linked to abuse of antibiotics amongst humans who self-medicate and also in veterinary medicine where use of antibiotics for prohylactic and therapeutic purpose in animals is uncontrolled thereby aiding the spread of antibiotic resistant strains from avians to human via food consumption. KEY WORDS: Resistance, Fluoroquinolone, E. coli Nigerian Journal of Health and Biomedical Sciences Vol.3(2) 2004: 73-78

Susceptibility patterns of enteroaggregative Escherichia coli associated with traveller's diarrhoea: emergence of quinolone resistance

Enteroaggregative Escherichia coli (EAggEC) isolates were identified as a cause of traveller's diarrhoea in 50 (9%) of 517 patients and their antimicrobial susceptibility was determined. Molecular epidemiological characterisation and investigation of the mechanisms of acquisition of quinolone resistance among nalidixic acid-resistant EAggEC strains was performed. Seventeen (34%) of 50 patients needed antimicrobial therapy, because of persistence of symptoms in nine cases and the severity of symptoms in eight cases. Ampicillin and tetracycline resistance was high, whereas chloramphenicol and co-trimoxazole showed moderate activity and amoxicillin plus clavulanic acid, nalidixic acid and ciprofloxacin showed very good activity. Resistance to nalidixic acid was demonstrated in three isolates, two from patients who had travelled to India. In all three strains the resistance was linked to mutations in the gyrA gene alone or in both gyrA and parC genes. Although ciprofloxacin shows excellent in-vitro activity and could be useful in the treatment of traveller's diarrhoea in patients travelling abroad, it may not be useful in patients who have journeyed to India or to Mexico.

The effect of pharmacokinetics on the bactericidal activity of ciprofloxacin and sparfloxacin against Streptococcus pneumoniae and the emergence of resistance.

The pharmacokinetics of ciprofloxacin and sparfloxacin were simulated in vitro and the effects of pharmacodynamic parameters on bactericidal activity and the emergence of quinolone resistance were examined for Streptococcus pneumoniae. Simulated serum concentrations of ciprofloxacin 500 mg bd were more rapidly bactericidal than sparfloxacin 200 mg bd, despite lower values for the key pharmacodynamic parameters (AUC/MIC and C(max)/MIC). This was possibly related to the slower oral absorption of sparfloxacin, which delayed achievement of the MIC compared with ciprofloxacin. In addition, sparfloxacin was shown to have similar bactericidal activity to ciprofloxacin when tested at the same concentrations, despite its four-fold better potency in MIC terms. The emergence of resistance following exposure to ciprofloxacin appeared to be dependent on the C(max)/MIC ratio and the AUC above the MIC, but not the AUC/MIC ratio. Resistance (at least four-fold increase in MIC) developed when the C(max)/MIC ratio was less than four or the AUC above the MIC was less than 10, and the resulting cultures regrew fully. In contrast, pneumococci with a two- to four-fold increase in sparfloxacin MIC were selected in the presence of serum concentrations of sparfloxacin despite a C(max)/MIC ratio higher than 12, but these isolates remained clinically susceptible by breakpoint MIC and their growth was inhibited by repeated dosage of sparfloxacin. Nevertheless, the selection of pneumococci with reduced susceptibility, and the possibility of further mutation to highly resistant strains supports the use of quinolones that rapidly eradicate pneumococci at conventional doses and achieve concentrations, in both serum and tissues, which exceed at least 4 x MIC.

In-vitro susceptibility of isolates of methicillin-resistant Staphylococcus aureus 1988-1993.

MICs for 423 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated in Hong Kong during 1988-1993 were performed for 15 antimicrobial agents: erythromycin, chloramphenicol, tetracycline, minocycline, gentamicin, netilmicin, trimethoprim, rifampicin, fusidic acid, ciprofloxacin, vancomycin, teicoplanin, sparfloxacin, clinafloxacin and RP 59500 (quinupristin/dalfopristin). Susceptibility to antibiotics generally remained stable throughout the study period, with the exception of the quinolones. Resistance to ciprofloxacin (breakpoint 4 mg/L) increased from a low of 9% in 1988 to a high of 82% in 1993. For sparfloxacin the corresponding figures were 9% and 78%, respectively. Six (1%) clinafloxacin-resistant strains were found. MIC50s and MIC90s of clinafloxacin increased from < or = 0.06 mg/L and 0.25 mg/L in 1988 to 1.0 mg/L and 2.0 mg/L, respectively, in 1993. All 423 strains were phage typed (typability 70%) and a diversity of phage types which changed during the observation period, with 13 dominating types, was observed. Ciprofloxacin resistance occurred in 12 of the dominating types, in 46 non-typable strains, and also in 23 strains of different, sporadically occurring types, indicating that the emergence of quinolone resistance was not due to dissemination of a single or few MRSA clones. The usefulness of quinolones in the treatment of MRSA infections is likely to be seriously constrained by the emergence of resistance. MICs for RP-59500 were < or = 2 mg/L for all isolates, suggesting that this agent merits further evaluation as an anti-MRSA agent. All MRSA remained susceptible to vancomycin and teicoplanin throughout the study period.

QUINOLONE PROPHYLAXIS IN NEUTROPENIC PATIENTS - EFFICACY VERSUS RESISTANCE

To assess the efficacy of quinolones in the prophylaxis of infections in neutropenic patients with acute non-lymphocytic leukemia, and to evaluate the emergence of quinolone resistance in two University Hospitals in Brazil, we retrospectively compared 101 consecutive episodes of neutropenia managed with quinolone prophylaxis between 1989 and November 1993, and 26 previous episodes without prophylaxis, and reviewed the results of in vitro sensitivity of Gram-negative strains to quinolones in the same period. Prophylaxis with quinolones resulted in less episodes of bacteremias (21% vs. 69%, p=10(-7)), including Gram-negative bacteremias (6% vs. 38%, p=10(-5)), with no statistically significant difference in the death rate (18% vs. 31%, p=0.14, 95% confidence interval -6-32). The resistance of Gramnegative strains to quinolones rose from 7% to 18% between 1990 and 1993 (p=10(-5)). The resistance against ceftazidime and amikacin, the agents used in the empirical antibiotic therapy, increased in the same proportion as the quinolones. Given the limited benefit of quinolones as prophylaxis and the increasing number of quinolone-resistant Gram-negative strains observed in our hospitals, the use of quinolones as prophylaxis must be seriously questioned. A stricter control of the use of quinolones in these hospitals might decrease resistance.

Quinolone resistance in Pseudomonas aeruginosa and Staphylococcus aureus. Development during therapy and clinical significance.

This review focuses on published information on the experimental as well as clinical data on the emergence of quinolone resistant isolates. In the course of clinical use of fluoroquinolones, only a sporadic emergence of quinolone resistance has been noted. The resistant organisms emerged particularly in certain clinical settings where large numbers of organisms frequently causing chronic infections are present and/or in loci where quinolone concentrations may not be optimal. In terms of occurrence in individuals, quinolone resistance has emerged most frequently in hospitalized and nursing-home patients with identifiable risk factors. Epidemiological studies revealed that in nearly all the cases studied one or one predominating quinolone resistant clone was selected that was horizontally transmitted. Thus, the emergence of quinolone resistance is not due to an independent selection of resistant strains in a number of patients, but to the clonal spread of one strain once it has acquired quinolone resistance. Therefore, the rate of quinolone resistance is very likely to be lower than reported.

Emergence of quinolone resistance among clinical isolates of methicillin-resistant Staphylococcus aureus in Ontario, Canada

One hundred two isolates of methicillin-resistant Staphylococcus aureus (MRSA) randomly selected from across the Canadian province of Ontario were tested for their susceptibility to ciprofloxacin, norfloxacin, and nalidixic acid by the agar dilution method. Forty-nine percent (50 of 102) had high levels of resistance to these quinolone compounds. For the 50 resistant isolates, ciprofloxacin and norfloxacin had high MICs for 90% of isolates (MIC90s) of 128 micrograms/ml and greater than 128 microgram/ml, respectively; for these isolates, the nalidixic acid MIC90 was greater than 640 micrograms/ml. The majority (98%) of the 50 isolates were also resistant to tobramycin (MIC90, greater than 128 micrograms/ml), while 42% of the isolates were resistant to gentamicin (MIC90, 64 micrograms/ml). Quinolone-resistant MRSA isolates were susceptible to bacteriophages from several groups, indicating independent selection of resistant strains. These results suggest that a reappraisal of the use of fluoroquinolones against MRSA in Canada is necessary.