zithromax and Dysentery--Bacillary

Annually, Shigella spp. cause ≈188 million cases of diarrheal disease globally, including 500,000 cases in the United States; rates of antimicrobial resistance are increasing. To determine antimicrobial resistance and risk factors in San Diego, California, USA, we retrospectively reviewed cases of diarrheal disease caused by Shigella flexneri and S. sonnei diagnosed during 2017-2020. Of 128 evaluable cases, S. flexneri was slightly more common than S. sonnei; most cases were in persons who were gay or bisexual cisgender men, were living with HIV, were unhoused, or used methamphetamines. Overall, rates of resistance to azithromycin, fluoroquinolones, ampicillin, and trimethoprim/sulfamethoxazole (TMP/SMX) were comparable to the most recent national data reported from the Centers for Disease Control and Prevention; 55% of isolates were resistant to azithromycin, 23% to fluoroquinolones, 70% to ampicillin, and 83% to TMP/SMX. The rates that we found for TMP/SMX were slightly higher than those in national data.

Topics: Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; California; Diarrhea; Drug Resistance, Bacterial; Dysentery, Bacillary; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Retrospective Studies; Shigella; Shigella sonnei; Trimethoprim, Sulfamethoxazole Drug Combination; United States

Diarrhoea is one of the most commonly occurring diseases. This article presents a review of the current state of the treatment of acute infectious diarrhoea, as well as of the most important pathogens. The general principles of the therapy of diarrhoea are exemplified, followed by a description of the targeted antimicrobial therapy of the most important bacterial gastrointestinal infections, including salmonellosis, shigellosis and Campylobacter infections, as well as infections with pathogenic Escherichia coli strains, yersiniosis and cholera. Diarrhoea caused by toxigenic Clostridium difficile strains has increased in incidence and in severity. These infections will therefore be described in detail, including important new aspects of treatment. Symptomatic therapy is still the most important component of the treatment of infectious diarrhoea. However, empirical antibiotic therapy should be considered for severely ill patients with a high frequency of stools, fever, bloody diarrhoea, underlying immune deficiency, advanced age or significant comorbidities. Increasing resistance, in particular against fluoroquinolones, must be taken into consideration. Therapy with motility inhibitors is not recommended for Shiga toxin-producing Escherichia coli (STEC) infections, Clostridium difficile infections (CDI), and severe colitis. The macrocyclic antibiotic fidaxomicin can reduce the rate of recurrent disease in CDI. Furthermore, evidence for the benefits of faecal microbiota transplantation as a treatment option for multiple recurrences of CDI is increasing. In conclusion, the treatment of acute diarrhoea is still primarily supportive. General empirical antibiotic therapy for acute diarrhoea is not evidence-based.

Topics: Acute Disease; Aminoglycosides; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Campylobacter Infections; Cholera; Ciprofloxacin; Diarrhea; Dysbiosis; Dysentery, Bacillary; Enterocolitis, Pseudomembranous; Escherichia coli Infections; Fidaxomicin; Gastroenteritis; Humans; Rifamycins; Rifaximin; Salmonella Infections; Shiga-Toxigenic Escherichia coli; Yersinia Infections

Shigella spp. are common enteric pathogens in captive non-human primates. Treatment of symptomatic infections involves supportive care and antibiotic therapy, typically with an empirical choice of antibiotic.. Twenty-four clinically ill, Shigella PCR-positive animals were randomly assigned to one of four treatment groups: single-dose ceftiofur crystalline free acid (CCFA), single-dose azithromycin gavage, a 5-day tapering azithromycin dose, or 7-day course of enrofloxacin. We hypothesized that all antimicrobial therapies would have similar efficacy.. Animals in all groups cleared Shigella, based on fecal PCR, and had resolution of clinical signs 2 weeks after treatment. Eight out of nine clinically ill and PCR-positive animals tested negative by fecal culture.. Single-dose CCFA, single-dose azithromycin, and a 5-day tapering course of azithromycin all performed as well as a 7-day course of enrofloxacin in eliminating Shigella infection. Fecal PCR may be a better diagnostic than culture for Shigella.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Dysentery, Bacillary; Enrofloxacin; Macaca mulatta; Macaca nemestrina; Shigella

Topics: Azithromycin; Cefixime; Chi-Square Distribution; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Dysentery, Bacillary; Feces; Female; Follow-Up Studies; Humans; Infant; Male; Paraguay; Prospective Studies; Reference Values; Risk Assessment; Severity of Illness Index; Shigella; Treatment Outcome

Treatment of shigellosis is currently limited by the high prevalence of multidrug-resistant strains of Shigella.. To determine the efficacy of azithromycin in the treatment of shigellosis.. Randomized, double-blind clinical trial.. Diarrhea treatment center in Dhaka, Bangladesh.. 70 men with shigellosis that had lasted 72 hours or less.. Patients stayed in the hospital for 6 days. Thirty-four patients were randomly assigned to receive 500 mg of azithromycin on study day 1, followed by 250 mg once daily for 4 days; 36 patients were assigned to receive 500 mg of ciprofloxacin every 12 hours for 5 days.. Clinical treatment failure was considered to have occurred if frank dysentery persisted for 72 hours after therapy began or if on study day 5 a patient had more than six stools, had any bloody-mucoid stools, had more than one watery stool, or had an oral body temperature exceeding 37.8 degrees C. Bacteriologic treatment failure was considered to have occurred if Shigella strains could be isolated from a stool sample after study day 2. Therapy was considered either clinically or bacteriologically successful in patients who completed therapy and did not meet criteria for failure.. Therapy was clinically successful in 28 (82%) patients who received azithromycin and 32 (89%) patients who received ciprofloxacin (difference, -7% [95% Cl, -23% to 10%]). Therapy was bacteriologically successful in 32 (94%) patients receiving azithromycin and 36 (100%) patients receiving ciprofloxacin (difference, -6% [Cl, -14% to 2%]). Peak serum concentrations of azithromycin were equal to the minimum inhibitory concentration (MIC) of the infecting Shigella strains, whereas serum concentrations of ciprofloxacin were 28 times the MIC. Stool concentrations of both drugs were more than 200 times the MIC.. Azithromycin is effective in the treatment of moderate to severe shigellosis caused by multidrug-resistant Shigella strains.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Double-Blind Method; Drug Resistance, Microbial; Dysentery, Bacillary; Follow-Up Studies; Humans; Male; Middle Aged; Shigella

Topics: Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; France; Humans; Microbial Sensitivity Tests; Plasmids; Shigella sonnei

We evaluated the burden of Shigella spp from children aged 0-59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018.. Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis.. The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold <35); shigellosis was higher in The Gambia (30.8%) than in Mali (9.3%) and Kenya (18.7%). Bloody diarrhea attributed to Shigella was more common in 24- to 59-month-old children (50.1%) than 0- to 11-month-old infants (39.5%). The Shigella flexneri serogroup predominated among cases (67.6% of isolates), followed by Shigella sonnei (18.2%), Shigella boydii (11.8%), and Shigella dysenteriae (2.3%). The most frequent S. flexneri serotypes were 2a (40.6%), 1b (18.8%), 6 (17.5%), 3a (9.0%), and 4a (5.1%). Drug-specific resistance among 353 (98.3%) Shigella cases with AMR data was as follows: trimethoprim-sulfamethoxazole (94.9%), ampicillin (48.4%), nalidixic acid (1.7%), ceftriaxone (0.3%), azithromycin (0.3%), and ciprofloxacin (0.0%).. A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin.

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Child, Preschool; Ciprofloxacin; Diarrhea; Dysentery, Bacillary; Humans; Infant; Infant, Newborn; Mali; Microbial Sensitivity Tests; Shigella

Multidrug-resistant (MDR) Shigella sonnei have become prevalent among men who have sex with men and have become a global public health concern. From June 2017 to April 2019, 32 men were infected with MDR S. sonnei acquired locally, in Montréal, which was suggestive of an outbreak. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), phylogenetic analysis, antimicrobial resistance and virulence characterization, and association to international clusters were performed. The outbreak strain was ceftriaxone- and azithromycin-resistant due to the acquisition of

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Ciprofloxacin; Drug Resistance, Bacterial; Dysentery, Bacillary; Genomics; Homosexuality, Male; Humans; Male; Microbial Sensitivity Tests; Phylogeny; Sexual and Gender Minorities; Shigella sonnei

Topics: Anti-Bacterial Agents; Azithromycin; Bangladesh; Drug Resistance, Bacterial; Dysentery, Bacillary; Humans; Macrolides; Microbial Sensitivity Tests; Shigella

In 2018, the Centers for Disease Control and Prevention and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community that offered a continuum of care from independent living through skilled nursing care. The investigation identified 24 culture-confirmed cases. Isolates were resistant to trimethoprim-sulfamethoxazole, ampicillin, and ceftriaxone, and had decreased susceptibility to azithromycin and ciprofloxacin.. To evaluate clinical and microbiologic response, we reviewed inpatient and outpatient medical records for treatment outcomes among the 24 patients with culture-confirmed S. sonnei infection. We defined clinical failure as diarrhea (≥3 loose stools per day) for ≥1 day after treatment finished, and microbiologic failure as a stool culture that yielded S. sonnei after treatment finished. We used broth microdilution to perform antimicrobial susceptibility testing, and whole genome sequencing to identify resistance mechanisms.. Isolates contained macrolide resistance genes mph(A) and erm(B) and had azithromycin minimum inhibitory concentrations above the Clinical and Laboratory Standards Institute epidemiological cutoff value of ≤16 µg/mL. Among 24 patients with culture-confirmed Shigella infection, 4 were treated with azithromycin; all had clinical treatment failure and 2 also had microbiologic treatment failure. Isolates were susceptible to ciprofloxacin but contained a gyrA mutation; 2 patients failed treatment with ciprofloxacin.. These azithromycin treatment failures demonstrate the importance of clinical breakpoints to aid clinicians in identifying alternative treatment options for resistant strains. Additionally, these treatment failures highlight a need for comprehensive susceptibility testing and systematic outcome studies, particularly given the emergence of multidrug-resistant Shigella among an expanding range of patient populations.

Topics: Anti-Bacterial Agents; Azithromycin; Ciprofloxacin; Disease Outbreaks; Drug Resistance, Bacterial; Dysentery, Bacillary; Humans; Macrolides; Microbial Sensitivity Tests; Retirement; Shigella; Shigella sonnei; Treatment Outcome; Vermont

Azithromycin is frequently used to treat shigellosis; however, clinical outcomes are uncertain.. We performed an observational cohort study in Bangladesh of patients with invasive diarrhea treated empirically with azithromycin. Susceptibility testing was performed by broth microdilution and disk diffusion post hoc on all Shigella isolates and clinical response was correlated with in vitro susceptibility.. There were 149 Shigella culture-positive patients in the primary analysis. Infection with Shigella with decreased susceptibility to azithromycin was significantly associated with persistence of diarrhea at day 5 (31% vs 12%; relative risk [RR], 2.66; 95% confidence interval [CI], 1.34-5.28), culture positivity at day 5 or 6 (35% vs 5%; RR, 5.26; 95% CI, 1.84-14.85), and a higher rate of overnight hospitalization (58% vs 39%; RR, 1.49; 95% CI, 1.06-2.09). Shigella flexneri was more common than Shigella sonnei (58% vs 36%); however, S. sonnei constituted most of the isolates with decreased susceptibility to azithromycin (67%) and most of the multidrug-resistant strains (54%); thus, poor clinical outcomes were associated with S. sonnei. The current epidemiological cutoff for S. flexneri of ≥16 µg/mL to define decreased susceptibility to azithromycin was clinically predictive of poor outcome. Patients with S. sonnei and a low MIC (4 µg/mL) still had elevated rates of persistent diarrhea and culture positivity.. This study documents worse clinical outcomes for S. flexneri with decreased susceptibility to azithromycin, as well as S. sonnei, and supports the utility of susceptibility testing and clinical breakpoints for azithromycin. S. sonnei is an emerging drug-resistant threat.. NCT03778125.

Topics: Anti-Bacterial Agents; Azithromycin; Bangladesh; Drug Resistance, Bacterial; Dysentery, Bacillary; Humans; Microbial Sensitivity Tests; Pharmaceutical Preparations; Shigella; Shigella sonnei

Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales.

Topics: Anti-Bacterial Agents; Australia; Azithromycin; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; England; Genetics, Population; Genome, Bacterial; Genomics; Genotype; Geography; Global Health; Humans; Microbial Sensitivity Tests; Phylogeny; Polymorphism, Single Nucleotide; Shigella sonnei; United States; Whole Genome Sequencing

In high-income countries, shigellosis is mainly found in travellers to high-risk regions or in men who have sex with men (MSM). This study investigated the genomic characteristics and the features of antimicrobial resistance of MSM-associated Shigella flexneri and Shigella sonnei circulating in Barcelona, Spain, elucidating their connectivity with contemporaneous Shigella spp. from other countries.. Antimicrobial susceptibility, whole-genome sequencing, genomic characterization and phylogenetic analysis were performed in MSM-associated Shigella spp. recovered from 2015 to 2019. Reference genomes of MSM-associated Shigella spp. were included for contextualization and to determine their connection with international outbreaks.. In total, 44 S. flexneri and 26 S. sonnei were identified among MSM. Overall, 80% showed resistance to azithromycin, 65.7% showed resistance to trimethoprim-sulphamethoxazole and 32.8% showed resistance to ciprofloxacin; 27.1% were resistant to all three antimicrobials. mphA and/or ermB, and qnrS and mutations in the quinolone resistance determining regions were found in the azithromycin- and ciprofloxacin-resistant isolates, respectively. Additionally, two isolates carried bla. This study investigated the circulation of lineages of S. flexneri and S. sonnei among MSM in Spain that were mainly resistant to first-/second-line oral treatments, and closely related to dominant MSM-associated lineages described previously in the UK and Australia. These data reinforce the urgent need for the implementation of public health measures focusing on the early detection and prevention of transmission of this emerging pathogen, which is contributing to the antimicrobial resistance crisis in sexually transmitted infections.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Ciprofloxacin; Disease Susceptibility; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; Genetic Variation; Genome; Geography; Homosexuality, Male; Humans; Male; Microbial Sensitivity Tests; Sexually Transmitted Diseases; Shigella; Spain; Whole Genome Sequencing

Shigellosis outbreaks caused by Shigella with decreased susceptibility to azithromycin (DSA-Shigella) among men who have sex with men (MSM) have been reported worldwide. We describe sexual health indicators and antimicrobial drug resistance for shigellosis cases in Minnesota, USA. We analyzed a sample of isolates received during 2012-2015 and cross-referenced cases with the Minnesota Department of Health Sexually Transmitted Disease Database to ascertain patients' HIV status and recent chlamydia, gonorrhea, and syphilis infections. Of 691 Shigella isolates, 46 (7%) were DSA-Shigella; 91% of DSA-Shigella patients were men, of whom 60% were living with HIV. Among men, those with DSA-Shigella infection had greater odds of living with HIV, identifying as MSM, or having a recent diagnosis of a sexually transmitted disease. DSA-Shigella was associated with MSM, HIV infection, and recent sexually transmitted disease. To decrease spread of DSA-Shigella, interventions targeted at communities at high risk are needed.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Dysentery, Bacillary; Female; Gonorrhea; HIV Infections; Homosexuality, Male; Humans; Male; Minnesota; Sexual and Gender Minorities; Sexually Transmitted Diseases; Shigella

Acute dysentery is a prevalent case of hospital admission in developing countries, whose most common cause is believed to be Shigella species. Treatment failure employing oral or intravenous antibiotics is an increasing problem among children with dysentery. This is a prospective descriptive study that aims to find the antibiotic resistance pattern of Shigella spp. isolates from children with acute diarrhea in three children's referral hospitals in Mashhad, northeast-Iran. Between February 2018 to September 2019, a total of 233 stool samples were collected from children with inflammatory diarrhea. Shigella spp. were identified by culture and biochemical standard tests. Moreover, polyvalent Shigella antisera were used for serogrouping. The antibiotic susceptibility was performed by disk diffusion method. During the 9-month study period, a total of 94 non-duplicate clinical Shigella spp. were identified by culture and biochemical tests. Based on slide agglutination with appropriate group-specific polyvalent antisera, Shigella sonnei (70.2%) was found to be the most prevalent Shigella spp. followed by S. flexeneri (23.4%), S. dysentery (1%). Among isolates, S. boydii was not detected and five isolates (5.3%) were nonserotypable isolates. The resistance rate of Shigella spp. to azithromycin, ceftriaxone, ciprofloxacin, co-trimoxazole, nalidixic acid, gentamicin, amoxicillin, ampicillin, doxycycline and cefixime was 25.5%, 43.6%, 3.8%, 82.9%, 15.9%, 26.6%, 40.4%, 57.4%, 41.4%, 22.3%, respectively. The results revealed that the resistance of Shigella spp. to the three most commonly utilized antibiotics (azithromycin, ceftriaxone and, cefixime) is too high to recommend them as empirical therapy for children with acute dysentery in this city.

Topics: Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Child; Drug Resistance, Bacterial; Dysentery, Bacillary; Feces; Hospitals; Humans; Iran; Microbial Sensitivity Tests; Prospective Studies; Referral and Consultation; Shigella

Shigella species remains a major diarrhoeagenic agent, affecting mostly children, with global high incidence and high mortality rate specially in developing areas. Although azithromycin is recommended for treatment of shigellosis, there are currently no CLSI susceptibility breakpoints, accordingly no routine antimicrobial susceptibility test is performed in the clinical laboratory. The purpose of this study was to estimate the prevalence, resistance profile and molecular epidemiology of azithromycin non-susceptible Shigella strains in Israel during a three year period. Shigella isolates (n = 1,170) referred to the National Reference Center during 2014-2016, were included in this study. Serotyping was performed by slide agglutination. Resistance genes, mph(A) and erm(B), were identified by PCR and the phenotype profile was determined by broth microdilution (BMD). Genetic relatedness was assessed by wgMLST. Decreased susceptibility to azithromycin (DSA) phenotype and genotype were detected in various Shigella species and serotypes related to diverse genetic backgrounds and antimicrobial profiles: 6% (26/423) of Shigella flexneri and 2% (16/747) of Shigella sonnei displayed DSA (MIC16 mg/L). Correlation of this phenotype with the presence of mph(A) and erm(B) genes was confirmed. All DSA-strains displayed resistance to ≥3 different antimicrobial classes. Among DSA-strains, 14% were resistant to quinolones and 5% displayed resistance to ceftriaxone. Most of these strains (32/42) were isolated from children in the southern and central regions of Israel. Clonality and significant relatedness was confirmed by PFGE and wgMLST. The presence of macrolide resistance genes among the different species and lineages reflects the transmissible nature of these genes. The emergence of DSA-Shigella reinforces the necessity to establish clinical breakpoints that would warrant routine testing, reporting and surveillance for this drug of choice.

Topics: Azithromycin; Drug Resistance, Bacterial; Dysentery, Bacillary; Genes, Bacterial; Genotype; Humans; Israel; Shigella flexneri; Shigella sonnei

Molecular characterization of virulence and antimicrobial resistance profiles were determined for Shigella species isolated from children with diarrhea in Fortaleza, Brazil. Fecal specimens were collected along with socioeconomic and clinical data from children with moderate to severe diarrhea requiring emergency care. Shigella spp. were isolated by standard microbiological techniques, and we developed 4 multiplex polymerase chain reaction assays to detect 16 virulence-related genes (VRGs). Antimicrobial susceptibility tests were performed using disk diffusion assays. S. flexneri and S. sonnei were the predominant serogroups. S. flexneri was associated with low monthly incomes; more severe disease; higher number of VRGs; and presence of pic, set, and sepA genes. The SepA gene was associated with more intense abdominal pain. S. flexneri was correlated with resistance to ampicillin and chloramphenicol, whereas S. sonnei was associated with resistance to azithromycin. Strains harboring higher numbers of VRGs were associated with resistance to more antimicrobials. We highlight the correlation between presence of S. flexneri and sepA, and increased virulence and suggest a link to socioeconomic change in northeastern Brazil. Additionally, antimicrobial resistance was associated with serogroup specificity in Shigella spp. and increased bacterial VRGs.

Topics: Ampicillin; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Brazil; Chloramphenicol; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Dysentery, Bacillary; Humans; Multiplex Polymerase Chain Reaction; Serine Proteases; Shigella flexneri; Shigella sonnei; Virulence

Horizontal gene transfer has played a role in developing the global public health crisis of antimicrobial resistance (AMR). However, the dynamics of AMR transfer through bacterial populations and its direct impact on human disease is poorly elucidated. Here, we study parallel epidemic emergences of multiple Shigella species, a priority AMR organism, in men who have sex with men to gain insight into AMR emergence and spread. Using genomic epidemiology, we show that repeated horizontal transfer of a single AMR plasmid among Shigella enhanced existing and facilitated new epidemics. These epidemic patterns contrasted with slighter, slower increases in disease caused by organisms with vertically inherited (chromosomally encoded) AMR. This demonstrates that horizontal transfer of AMR directly affects epidemiological outcomes of globally important AMR pathogens and highlights the need for integration of genomic analyses into all areas of AMR research, surveillance and management.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Dysentery, Bacillary; Gene Transfer, Horizontal; Genome-Wide Association Study; Homosexuality, Male; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Phenotype; Phylogeny; Plasmids; Shigella; Time Factors; Young Adult

Antimicrobial overuse contributes to antimicrobial resistance. Empiric use of antimicrobials for diarrheal illness is warranted only in a minority of cases, because of its self-limiting nature and multifactorial etiology. This study aims to describe the factors contributing to antimicrobial overuse for diarrheal disease among children less than 5 years of age in rural Bangladesh. A total of 3,570 children less than 5 years of age presenting with diarrhea in a tertiary level hospital were enrolled in the study. The rate of antimicrobial use at home was 1,395 (39%), compared with 2,084 (89%) during a hospital visit. In a multivariate analysis, factors associated with antimicrobial use at home included residence located more than 5 miles from a hospital; use of zinc and oral rehydration salts at home; vomiting; greater than 10 stools per 24 hours; diarrheal duration greater than 3 days; and rotavirus diarrhea (

Topics: Anti-Infective Agents; Azithromycin; Bangladesh; Child, Preschool; Cross-Sectional Studies; Diarrhea; Dysentery, Bacillary; Erythromycin; Feces; Female; Humans; Infant; Male; Multivariate Analysis; Prescription Drug Overuse; Risk Factors; Rotavirus Infections; Rural Population; Serotyping; Shigella; Tertiary Care Centers; Time Factors

To examine antimicrobial susceptibility patterns and predictors of resistance among Shigella isolates in New South Wales (NSW), Australia during 2013-14 with emphasis on azithromycin.. Cross-sectional analysis of all shigellosis cases (160) notified to public health authorities in NSW, Australia was performed.. Among 160 Shigella isolates tested, 139 (86.9%) were susceptible to azithromycin, 104 (65.0%) to ciprofloxacin and 38 (23.7%) to co-trimoxazole. Ciprofloxacin resistance was 1.9 times more common in infections acquired in Australia compared with those acquired overseas, while azithromycin resistance was 8.5 times more common in males.. We recommend ongoing reconsideration of guidelines for the treatment of shigellosis based on emerging resistance patterns. First-line therapy may need to be reconsidered based on local resistance rates due to common resistance to co-trimoxazole and ciprofloxacin. We recommend culture and susceptibility testing for suspected and proven shigellosis. Azithromycin susceptibility breakpoints for Shigella species may need to be species specific.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Australia; Azithromycin; Child; Child, Preschool; Ciprofloxacin; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; Female; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; New South Wales; Practice Guidelines as Topic; Shigella; Young Adult

The aim of this study was to detect the decreased susceptibility to azithromycin (DSA) and associated mechanisms in Shigella from China. Three hundred and ninety-two Shigella isolates, including 134 Shigella flexneri and 258 Shigella sonnei isolates, were examined for minimum inhibitory concentrations (MICs) and zone sizes to azithromycin by broth microdilution and disk diffusion methods, respectively. The MICs were compared with corresponding zone diameters to find whether there was uniformity between both tests. Twelve macrolide-resistant genes located on mobile elements were determined for the DSA isolates by PCR, and chromosomal efflux pump activity was analyzed using Phe-Arg-β-naphthylamide inhibition test and quantitative real-time PCR. Shigella isolates displayed MICs of 0.125-512 μg/ml and zone sizes of 6-26 mm against azithromycin. There were 80 (20.4%) isolates to be DSA. No significant difference was found between the DSA rates of S. flexneri and S. sonnei isolates (p = 0.052). There was an intimate relativity between MICs and zone diameters (p < 0.001). Only the plasmid-borne mphA conferring high-level DSA was detected in 55.0% (44/80) DSA-Shigella isolates. This study highlighted the prevalence of DSA-Shigella and mphA in the region studied. Clinical laboratories and clinicians should pay attention to the elevated azithromycin MICs in Shigella spp.

Topics: Anti-Bacterial Agents; Arginine; Azithromycin; Bacterial Proteins; Biological Transport; China; Drug Resistance, Bacterial; Dysentery, Bacillary; Gene Expression; Humans; Microbial Sensitivity Tests; Phosphotransferases (Alcohol Group Acceptor); Plasmids; Shigella flexneri; Shigella sonnei

Approximately 20% of Shigella isolates tested in New York City, New York, USA, during 2013-2015 displayed decreased azithromycin susceptibility. Case-patients were older and more frequently male and HIV infected than those with azithromycin-susceptible Shigella infection; 90% identified as men who have sex with men. Clinical interpretation guidelines for azithromycin resistance and outcome studies are needed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Coinfection; Drug Resistance, Bacterial; Dysentery, Bacillary; Female; HIV Infections; Homosexuality, Male; Humans; Infant; Infant, Newborn; Male; Middle Aged; New York City; Shigella; Young Adult

Topics: Australia; Azithromycin; Drug Resistance, Bacterial; Dysentery, Bacillary; Humans

Topics: Anti-Bacterial Agents; Azithromycin; Canada; Ciprofloxacin; Coinfection; Drug Resistance, Bacterial; Dysentery, Bacillary; History, 21st Century; HIV Infections; Humans; Microbial Sensitivity Tests; Population Surveillance; Shigella flexneri

We report an outbreak of azithromycin-nonsusceptible Shigella flexneri 3a infection in Taiwan associated with men who have sex with men. The bacterial strains belonged to the sublineage A of a recently reported outbreak lineage associated with men who have sex with men, characterized by reduced azithromycin susceptibility and circulation in shigellosis low-risk regions.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Disease Outbreaks; Drug Resistance, Bacterial; Dysentery, Bacillary; Homosexuality, Male; Humans; Male; Sexually Transmitted Diseases; Shigella flexneri; Taiwan; Young Adult

Topics: Adult; Aged; Australia; Azithromycin; Disease Outbreaks; Drug Resistance, Bacterial; Dysentery, Bacillary; Homosexuality, Male; Humans; Male; Middle Aged; Young Adult

Topics: Azithromycin; Drug Resistance, Bacterial; Dysentery, Bacillary; Female; Humans; Male; Sexually Transmitted Diseases

Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK.. We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships.. We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated atypical infection patterns (eg, reinfection).. We identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM.. Wellcome Trust (grant number 098051).

Topics: Adolescent; Adult; Aged; Azithromycin; Child; Child, Preschool; Cross-Sectional Studies; Disease Outbreaks; Drug Resistance, Bacterial; Dysentery, Bacillary; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Phylogeny; Risk; Sexually Transmitted Diseases; Shigella flexneri; Travel; United Kingdom; Young Adult

Increasing rates of shigellosis among adult males, particularly men who have sex with men (MSM), have been documented in the United States, Canada, and Europe, and MSM appear to be at greater risk for infection with shigellae that are not susceptible to ciprofloxacin or azithromycin. Azithromycin is the first-line empiric antimicrobial treatment for shigellosis among children and is a second-line treatment among adults. Isolates collected in 2014 in two U.S. cities from outbreaks of shigellosis displayed highly similar pulsed-field gel electrophoresis (PFGE) patterns and decreased susceptibility to azithromycin (DSA). This report summarizes and compares the findings from investigations of the two outbreaks, which occurred among MSM in metropolitan Minneapolis-St. Paul, Minnesota, and Chicago, Illinois.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Chicago; Disease Outbreaks; Drug Resistance, Bacterial; Dysentery, Bacillary; Electrophoresis, Gel, Pulsed-Field; Homosexuality, Male; Humans; Male; Middle Aged; Minnesota; Shigella sonnei; Young Adult

Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Dysentery, Bacillary; HIV Infections; Humans; Male; Shigella flexneri; Treatment Failure

Bacteria of the genus Shigella cause approximately 500,000 illnesses each year in the United States. Diarrhea (sometimes bloody), fever, and stomach cramps typically start 1-2 days after exposure and usually resolve in 5-7 days. For patients with severe disease, bloody diarrhea, or compromised immune systems, antibiotic treatment is recommended, but resistance to traditional first-line antibiotics (e.g., ampicillin and trimethoprim-sulfamethoxazole) is common. For multidrugresistant cases, azithromycin, the most frequently prescribed antibiotic in the United States, is recommended for both children and adults. However, not all Shigellae are susceptible to azithromycin. Nonsusceptible isolates exist but are not usually identified because there are no clinical laboratory guidelines for azithromycin susceptibility testing. However, to monitor susceptibility of Shigellae in the United States, CDC's National Antimicrobial Resistance Monitoring System (NARMS) has, since 2011, routinely measured the azithromycin minimum inhibitory concentration (MIC) for every 20th Shigella isolate submitted from public health laboratories to CDC, as well as outbreak-associated isolates. All known U.S. Shigella isolates with decreased susceptibility to azithromycin (DSA-Shigella), and the illnesses caused by them, are described in this report.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Bacterial; Dysentery, Bacillary; Female; Homosexuality, Male; Humans; Infant; Male; Middle Aged; Shigella; United States; Young Adult

During 2012-2013 in Montreal, Canada, 4 locally acquired Shigella spp. pulse types with the mph(A) gene and reduced susceptibility to azithromycin were identified from 9 men who have sex with men, 7 of whom were HIV infected. Counseling about prevention of enteric sexually transmitted infections might help slow transmission of these organisms.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Coinfection; Drug Resistance, Bacterial; Dysentery, Bacillary; Female; Genes, Bacterial; Homosexuality, Male; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Phosphotransferases (Alcohol Group Acceptor); Public Health Surveillance; Quebec; Sexually Transmitted Diseases; Shigella

Topics: Anti-Bacterial Agents; Azithromycin; Child; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; Female; Humans; Male; Microbial Sensitivity Tests; Shigella sonnei; United States

In May 2012, the Los Angeles County Department of Public Health's Acute Communicable Disease Control Unit and Environmental Health, Food, and Milk Program investigated an outbreak of shigellosis associated with a private bridge club. This investigation documented the first known transmission of Shigella sonnei with decreased susceptibility to azithromycin in the United States.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Disease Outbreaks; Drug Resistance, Bacterial; Dysentery, Bacillary; Female; Humans; Los Angeles; Male; Microbial Sensitivity Tests; Middle Aged; Shigella sonnei

The aim of this study was to develop and analyze in vitro azithromycin (AZM)-resistant mutants of Escherichia coli and Shigella boydii. Three clinical isolates of E. coli and one S. boydii isolated from feces samples collected from children under 5 years of age with diarrhea in Lima, Peru were inoculated onto Mueller-Hinton plates containing increasing serial dilutions of AZM ranging from their specific minimal inhibitory concentration (2 or 4 mg/l) to 64 mg/l. From these plates, 16 AZM-resistant mutants were selected to determine the stability of the resistance and the presence of cross resistance with other antibiotics. The role of Phe-Arg-β-Naphthylamide (PAβN)-inhibitible efflux pumps as well as the presence of mutations in the rplV, rplD, and rrlH (23S rRNA) genes and alterations in the outer membrane profiles were determined in these 16 mutants. The rate of mutation ranged from < 2.70×10(-10) to 2.17×10(-7) for E. coli and from < 9.58×10(-10) to 1.05×10(-8) for S. boydii. E. coli mutants showed an increase in the AZM-MIC up to sixfold with one strain achieving a MIC >256 mg/l. In contrast, S. boydii only presented increases of up to twofold in MIC levels. All the strains obtained, but one showed stable AZM resistance. In the presence of PAβN, the AZM MICs decreased to parental levels in Shigella mutants, while no MIC returned to parental levels among the E. coli mutants. No cross resistance to other classes of antibiotics was found. These results show the relevance of PAβN-inhibitible efflux pumps in the basal levels and development of AZM resistance. Further studies to characterize the remaining unidentified mechanisms of AZM resistance are needed.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Dipeptides; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Dysentery, Bacillary; Escherichia coli; Escherichia coli Infections; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Mutation; Shigella boydii

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Shigella sonnei; United States

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; Female; Fluoroquinolones; Humans; Shigella flexneri; Travel

To investigate azithromycin susceptibility in Shigella sonnei in the United States, we examined the azithromycin minimum inhibitory concentrations (MICs) of outbreak and routine human S. sonnei isolates. Isolate susceptibility clustered at 8 mg/L, but three isolates displayed higher MICs (>64  mg/L) to azithromycin. All three isolates contained a plasmid-encoded mphA gene, known to encode a macrolide-2'-phosphotransferase enzyme. Transformation of the mphA gene into Escherichia coli DH10B allowed the transfer of decreased susceptibility to azithromycin. Although these isolates might traditionally be defined as resistant, there are no established breakpoints for resistance to confirm that treatment of these isolates with azithromycin would fail, which complicates susceptibility screening.

Topics: Anti-Bacterial Agents; Azithromycin; Disease Outbreaks; Drug Resistance, Bacterial; Dysentery, Bacillary; Humans; Microbial Sensitivity Tests; Phosphotransferases (Alcohol Group Acceptor); Plasmids; Polymerase Chain Reaction; Shigella sonnei; United States

The need to limit unnecessary antibiotic treatments and recent studies with unusual antibiotics in pediatrics (fluoroquinolones) or in digestive tract infections (azithromycin) have led to update the treatment of acute gastro-enteritis. In 2007, the European Society for Pediatric Infectious Diseases and the European Society for Gastroenterology Hepatology and Nutrition have issued guidelines. The proven shigellosis as well as the strong suspicion have to be treated promptly with antibiotics, mainly azithromycin. There is no argument to treat moderate salmonella gastroenteritis or carriage. However, the severe cases and those occurring in high risk patient must be treated (ciprofloxacin or ceftriaxone). It is recommended to treat diarrhoea due to Campylobacter jejuni in case of early diagnosis. The presumptive antibiotic treatment should be limited but can not be dismissed, in invasive cases gastro-enteritis, especially in traveller children.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Campylobacter Infections; Campylobacter jejuni; Ceftriaxone; Child; Ciprofloxacin; Diarrhea; Dysentery, Bacillary; Escherichia coli Infections; Gastroenteritis; Humans; Salmonella Infections

Topics: Adult; Anti-Bacterial Agents; Azithromycin; beta-Lactamases; beta-Lactams; Drug Resistance, Bacterial; Dysentery, Bacillary; Haiti; Humans; Male; Microbial Sensitivity Tests; Shigella sonnei; Travel

Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p < 0.01) and nalidixic acid (from 19% to 51%, p < 0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to > or =3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p < 0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] > or =32 microg/mL) and had 10-fold higher MIC90 (0.25 microg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 microg/mL) and nalidixic acid (MIC 128 micdrog/mL) and low to ceftriaxone (MIC 0.023 microg/mL). Conjugative R-plasmids-encoded extended-spectrum beta-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution.

Topics: Anti-Bacterial Agents; Azithromycin; Bangladesh; Ceftriaxone; Ciprofloxacin; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; Humans; Microbial Sensitivity Tests; Sentinel Surveillance; Shigella; Species Specificity; Treatment Outcome

Antimicrobial-resistant Shigella sonnei is a growing problem in the United States and poses treatment challenges particularly among children. Azithromycin is recommended as an alternative oral agent for shigellosis.. All isolates of Shigella submitted to Johns Hopkins clinical laboratory during the outbreak year (2002) were compared with a historical comparison group (1996-2000). Isolates were considered multiresistant if they were resistant to ampicillin and trimethoprim-sulfamethoxazole (TS). Selected outbreak and reference isolates were tested for azithromycin susceptibility by E-test, disk diffusion and broth dilution methods.. Between 1996-2000, among the 111 isolates submitted, 63% were from pediatric patients; 63% of isolates were resistant to ampicillin and 12% to TS. In 2002, among the 205 isolates submitted, 82% were from pediatric patients; 91% isolates were resistant to ampicillin and 67% to TS. The proportion of multiresistant isolates increased from 6% in 1996 to 65% in 2002 (P < 0.05). Azithromycin susceptibility by E-test and disk diffusion demonstrated 2 zones of inhibition for S. sonnei. Interpretation using the inner zone resulted in higher MICs (minimal inhibitory concentration) compared with the outer zones by E-test (P < 0.0001) and disk diffusion (P < 0.0001).. With increasing interest in using azithromycin for shigellosis, clinical laboratories should be aware of the interpretation difficulty caused by the dual-zone phenomenon seen with E-test and disk diffusion methods for S. sonnei.

Topics: Adolescent; Ampicillin; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Dysentery, Bacillary; Humans; Infant; Microbial Sensitivity Tests; Shigella sonnei; Trimethoprim, Sulfamethoxazole Drug Combination

In an outbreak of shigellosis in a kibbutz in Northeastern Israel, oral nalidixic acid failed clinically in 35% and microbiologically in 28.4% of 14 children as compared with no clinical and microbiologic failure in 25 children who were treated with oral azithromycin (P < 0.01 and 0.012, respectively). Thus azithromycin could be a suitable alternative to nalidixic acid.

Topics: Administration, Oral; Adolescent; Azithromycin; Child; Child, Preschool; Cohort Studies; Disease Outbreaks; Dose-Response Relationship, Drug; Drug Administration Schedule; Dysentery, Bacillary; Female; Follow-Up Studies; Humans; Infant; Israel; Male; Nalidixic Acid; Probability; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome