Acute diarrhea with blood: diagnosis and drug treatment / Diarreia aguda com sangue: diagnóstico e tratamento medicamentoso

Abstract Objective To restate the epidemiological importance of Shigella in acute diarrhea with blood, providing an overview of the treatment and stressing the need for the correct indication of antibiotic therapy. Sources of Data A search was carried out in the Medline and Scopus databases, in addition to the World Health Organization scientific documents and guidelines, identifying review articles and original articles considered relevant to substantiate the narrative review. Synthesis of Data Different pathogens have been associated with acute diarrhea with blood; Shigella was the most frequently identified. The manifestations of shigellosis in healthy individuals are usually of moderate intensity and disappear within a few days. There may be progression to overt dysentery with blood and mucus, lower abdominal pain, and tenesmus. Conventional bacterial stool culture is the gold standard for the etiological diagnosis; however, new molecular tests have been developed to allow the physician to initiate targeted antibacterial treatment, addressing a major current concern caused by the increasing resistance of Shigella. Prevention strategies include breastfeeding, hygiene measures, health education, water treatment, and the potential use of vaccines. Conclusions Acute diarrhea is an important cause of mortality in children under 5 years and shigellosis is the leading cause of acute diarrhea with blood worldwide. The current concern is the increase in microbial resistance to the recommended antibiotics, which brings an additional difficulty to therapeutic management. Although no vaccine is yet available against Shigella, several candidates are undergoing clinical trials, and this may be the most cost-effective preventative measure in future.

Resumo Objetivo Reiterar a importância epidemiológica da Shigella na diarreia aguda com sangue, fornecer uma visão geral do tratamento e ressaltar a necessidade da correta indicação da antibioticoterapia. Fontes dos dados Realizada pesquisa nos bancos de dados Medline e Scopus, além de documentos científicos e diretrizes da Organização Mundial da Saúde, com a identificação de artigos de revisão e artigos originais considerados relevantes para fundamentar a revisão do tipo narrativa. Síntese dos dados Diferentes patógenos têm sido associados à diarreia aguda com sangue, a Shigella é o mais frequente. As manifestações da shigelose em indivíduos saudáveis são geralmente de intensidade moderada e desaparecem em poucos dias. Pode haver progressão para disenteria franca com sangue e muco, dor em abdome inferior e tenesmo. A coprocultura bacteriana convencional é o padrão-ouro para o diagnóstico etiológico, porém novos testes moleculares foram desenvolvidos, os quais permitem ao médico iniciar tratamento antibacteriano direcionado, sanar uma grande preocupação atual, devido à crescente resistência da Shigella. Estratégias de prevenção incluem aleitamento, medidas de higiene, educação em saúde, tratamento da água e o potencial uso de vacinas. Conclusões A diarreia aguda é uma importante causa de mortalidade em crianças com menos de cinco anos e a shigelose é a principal causa de diarreia aguda com sangue em todo o mundo. A preocupação atual é o aumento da resistência microbiana aos antibióticos preconizados, o que traz uma dificuldade adicional ao manejo terapêutico. Embora ainda não exista vacina disponível para Shigella, várias candidatas estão em fase de testes clínicos, podem futuramente ser a medida preventiva mais custo-efetiva.

Dysentery by CTX-M Type ESBL Producing Shigella flexneri / Disentería por Shigella flexneri productora de BLEE tipo CTX-M

According to the World Health Organization, diarrheal infections cause 525 000 deaths of children under five years of age every year, and shigellosis. Shigellosis is a relevant cause of dysentery, which increases the morbidity and mortality in pediatric patients. Therefore, emergingthe emergence of antimicrobial resistant strains of Shigella is a concerningworrisome problem worldwide. We report the case of a 7-year-old patient with acute dysentery caused by CTX-M Type ESBL Producing Shigella flexneri, being. This was the first case treated in the Specialties Hospital of Specialties of the Armed Forces N°1, in Quito, Ecuador. The antibiogram demonstrated sensibilityshowed sensitivity to ampicillin-sulbactam. As a result, after five days of microbiologically directed treatment, the patient improved his condition without relapse. Proper clinical diagnoses and accurate laboratory studies like stool culture and antibiogram are crucial to givingindicate an appropriate therapy in infections caused by Shigella and other enteric bacilli(AU)

Según la Organización Mundial de la Salud, las infecciones diarreicas provocan 525 000 muertes de niños menores de cinco años de edad cada año. La shigelosis es una causa importante de disentería que aumenta la morbilidad y mortalidad de los pacientes pediátricos. Es por eso que el surgimiento de cepas de Shigella resistentes a los antibióticos es un preocupante problema a nivel mundial. Presentamos el caso de un paciente de 7 años de edad con disentería aguda provocada por Shigella flexneri productora de BLEE tipo CTX-M. Se trata del primer caso tratado en el Hospital de Especialidades de las Fuerzas Armadas Nº 1, en Quito, Ecuador. El antibiograma mostró sensibilidad a la combinación ampicilina/sulbactam. Al cabo de cinco días de tratamiento microbiológico, el paciente mejoró su estado y no se produjeron recaídas. Un diagnóstico clínico correcto, así como estudios precisos de laboratorio como los cultivos de heces y los antibiogramas, son vitales para indicar una terapia apropiada en las infecciones causadas por Shigella y otros bacilos entéricos(AU)

The importance of integrons for development and propagation of resistance in Shigella: the case of Latin America

Abstract In Latin America, the disease burden of shigellosis is found to coexist with the rapid and rampant spread of resistance to commonly used antibiotics. The molecular basis of antibiotic resistance lies within genetic elements such as plasmids, transposons, integrons, genomic islands, etc., which are found in the bacterial genome. Integrons are known to acquire, exchange, and express genes within gene cassettes and it is hypothesized that they play a significant role in the transmission of multidrug resistance genes in several Gram-negative bacteria including Shigella. A few studies have described antibiotic resistance genes and integrons among multidrug resistant Shigella isolates found in Latin America. For example, in Brazil, Bolivia, Chile, Costa Rica and Peru, class 1 and class 2 integrons have been detected among multidrug resistant strains of Shigella; this phenomenon is more frequently observed in S. flexneri isolates that are resistant to trimethoprim, sulfamethoxazole, streptomycin, ampicillin, chloramphenicol, and tetracycline. The gene cassette sul2, which is frequently detected in Shigella strains resistant to the sulfonamides, suggests that the sulfonamide-resistant phenotype can be explained by the presence of the sul2 genes independent of the integron class detected. It is to be noted that sul3 was negative in all isolates analyzed in these studies.The high frequency of sulfonamide (as encoded by sul2) and trimethoprim resistance is likely to be a result of the recurrent use of trimethoprim sulfamethoxazole as a popular regimen for the treatment of shigellosis. The observed resistance profiles of Shigella strains confirm that ampicillin and trimethoprim-sulfamethoxazole are ineffective as therapeutic options. In-depth information regarding antibiotic resistance mechanism in this pathogen is needed in order to develop suitable intervention strategies. There is a pressing need for regional and local antimicrobial resistance profiling of Shigella to be included as a part of the public health strategy.

Shigella in Brazilian children with acute diarrhoea: prevalence, antimicrobial resistance and virulence genes

Diarrhoeal disease is still considered a major cause of morbidity and mortality among children. Among diarrhoeagenic agents, Shigella should be highlighted due to its prevalence and the severity of the associated disease. Here, we assessed Shigella prevalence, drug susceptibility and virulence factors. Faeces from 157 children with diarrhoea who sought treatment at the Children's Hospital João Paulo II, a reference children´s hospital in Belo Horizonte, state of Minas Gerais, Brazil, were cultured and drug susceptibility of the Shigella isolates was determined by the disk diffusion technique. Shigella virulence markers were identified by polymerase chain reaction. The bacterium was recovered from 10.8% of the children (88.2% Shigella sonnei). The ipaH, iuc, sen and ial genes were detected in strains isolated from all shigellosis patients; set1A was only detected in Shigella flexneri. Additionally, patients were infected by Shigella strains of different ial, sat, sen and set1A genotypes. Compared to previous studies, we observed a marked shift in the distribution of species from S. flexneri to S. sonnei and high rates of trimethoprim/sulfamethoxazole resistance.

Antimicrobial resistance in Shigella - rapid increase & widening of spectrum in Andaman Islands, India.

Background & objectives: Shigellosis is known to be a major cause of acute childhood diarrhoea in Andaman & Nicobar Islands, India. Rapid emergence of antibiotic resistance warrants continuous monitoring of sensitivity pattern of bacterial isolates. We report here the salient findings of an ongoing study on shigellosis in Andaman Islands, India, with regards to change in drug resistance pattern during the past one decade. Method: During 2006-2009, stools samples from 412 paediatric diarrhoea patients were collected and processed for isolation and identification of Shigella spp. Susceptibility to 22 antimicrobial drugs was tested and MICs were determined for 3rd generation cephalosporins, quinolones, amoxicillin-clavulanic acid combination and gentamicin. Drug susceptibility pattern of these isolates were compared with that of 33 isolates obtained during 2000-2002. Results: Shigella isolates were recovered from 50 of 412 stool samples processed. Resistance to ampicillin, nalidixic acid, tetracycline and ciprofloxacin was observed in 100, 96, 94 and 82 per cent of the isolates, respectively. The frequency of resistance to these drugs was significantly (P<0.001) higher than that observed during 2000-2002. Resistance to seven drugs was observed in 2000-2002, whereas resistance to 21 drugs was seen during 2006-2009. The number of drug resistance pattern increased from 13 in 2000-2002 to 43 in 2006-2009. Resistance to newer generation fluoroquinolones, 3rd generation cephalosporins and augmentin, which was not observed during 2000-2002, appeared during 2006-2009. Interpretation & conclusions: The frequency of resistance among Shigella isolates has increased substantially between 2000-2002 and 2006-2009 and the spectrum of resistance has widened. At present, the option for antimicrobial therapy in shigellosis in Andaman is limited to a small number of drugs. Continuous local monitoring of resistance patterns is necessary for the appropriate selection of empirical antimicrobial therapy.

Ceftriaxone resistant Shigella Flexneri, an emerging problem.

Shigellosis is a disease of public health importance in developing countries. It may cause self-limited diarrhea to severe dysentery. Emergence of multi drug resistant (MDR) strains is a growing concern globally. Ceftriaxone and ciprofloxacin are the drugs of choice for MDR cases. Here, we report a case of MDR Shigella flexneri from an immunocompromised patient. The strain was resistant to ceftriaxone [minimum inhibitory concentration (MIC) ≥ 64 μg/ml], limiting the treatment option. Simultaneously, the strain was also found to be resistant to ciprofloxacin (MIC ≥ 4 μg/ml). However, it was susceptible to ceftazidime (MIC 4 μg/ml). This is the first case of ceftriaxone resistant Shigella spp. reported from our hospital.

Surveillance of antibiotic susceptibility pattern among shigella flexneri strain isolated in Nagpur district during three years period, January 2009-January 2012.

Objective : In the few cases of childhood dirrhea that require the antimicrobial therapy, the correct choice of the drug depends on detailed previous knowledge of local strains and pattern of antimicrobial resistance. Shigellosis is one of the most improtant examples of this group of intestinal infections. In order to establish such parameters in Nagpur city, this study was carried out to determine the antimcrobial resistance profile of Shigella flexneri isolated from patients suffering from diahhrea admitted to Various hoapitals in Nagpur district, India. Materials and Methods: The study included 110 stool samples collected from patients during the 3 year period. All the isolates were characterized and confirmed by VITEK® 2 GN ID cards and antimicrobial susceptibility was tested by VITEK® 2 AST test cards. Results: We received 73 positive cultures of S. flexneri out of 110 stool samples during three year periods of January 2009 to January 2012. S. flexneri strains presented a high resistance rate to Ampicillin (100%), Chloramphenicol (76.71%), Trimethoprime-sulfamethaxazole (TMP-SMZ) (68.49%) and low resistance to third- and fourth-generation Cephalosporin. None of the isolates was found to be resistant to Ciprofloxacin (MIC ≥ 4), Norfloxacin (MIC ≥12), and Nalidixic acid (MIC ≥30). Conclusion: Our results provide data on antimicrobial resistance to choose a proper antibiotic for the treatment of Shigellosis in our country. According to current findings, Quinolones and Cephalosporins are the drug of choice for the diarrheic patients. In conclusion, systematic monitoring is needed to identify changes in the antimicrobial resistance.

Extended-spectrum beta-lactamase production in sbigella flexneri

Emergence of multidrug-resistant strains of Shigella is a growing concern across the globe. Third-generation cephalosporins are used for treating infections caused by multidrug-resistant Shigellae. However, resistance to these cephalosporin antibiotics due to extended-spectrum beta-lactamases, has emerged as a new problem. So far extended-spectrum beta-lactamases producing Shigella has not been reported from Pakistan. We report such a case in Shigella flexneri from an 8-year old girl with acute dysentery

Prevalence of Shigella serogroups and their antimicrobial resistance patterns in southern Trinidad.

The serogroup distribution and antimicrobial susceptibility patterns of Shigella isolates obtained from stool specimens of persons with acute diarrhoea in community-based studies from southern Trinidad during 1997-2006 were reviewed. Of the 5,187 stool specimens, 392 (8%) were positive for Shigella organisms. From these 392 isolates, 88.8% were recovered from children aged >0-10 year(s). Shigella sonnei was the most frequently-isolated serogroup (75%), followed by S. flexneri (19%), S. boydii (4.1%), and S. dysenteriae (1.8%). S. flexneri was the major isolate among the >20-30 years age-group. The most common drug resistance among all age-groups was to ampicillin. All strains of S. flexneri, S. boydii, and S. dysenteriae were fully susceptible to aztreonam, gentamicin, and ciprofloxacin. S. sonnei, the most common species isolated, showed resistance to all antibiotics tested. The data showed that, throughout the study period, the resistance to commonly-used drugs was relatively low. Since resistance to several drugs seems to be emerging, continuous monitoring of resistance patterns is mandatory for the appropriate selection of empiric antimicrobial drugs in the therapy of suspected cases of shigellosis.

Increasing spectrum in antimicrobial resistance of Shigella isolates in Bangladesh: resistance to azithromycin and ceftriaxone and decreased susceptibility to ciprofloxacin.

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.

Shigella isolates of Nepal: changes in the incidence of shigella subgroups and trends of antimicrobial susceptibility pattern.

OBJECTIVES: Shigellosis is an important cause of bloody diarrhoea in all age groups, especially in children. A retrospective study was done to analyse the pattern of shigella isolates and the antimicrobial susceptibility trend of these shigella isolated at different hospitals of Nepal from Jan, 2003- Dec, 2005. MATERIALS AND METHODS: A total of 118 Shigella species isolated at nine different hospital laboratories of Nepal were reported to National Public Health Laboratory during January, 2003- December 2005 .The isolates were tested for the confirmation of identification and antimicrobial susceptibility pattern by standard bacteriological techniques. RESULTS: Of the 118 Shigella isolates reported, Shigella flexneri 51 (43.22%) was the predominant of the four species followed by Shigella dysenteriae 49(41.52 %) , Shigella boydii (7.62%) and Shigella sonnei (7.62%).But the yearly distribution of the Shigella isolates in 2003 and 2004 showed that Shigella dysenteriae was the most common of the four species. In 2005, a shift in the species was noted as Sh flexneri replaced Sh dysenteriae and became the most prevalent species. The percentage of Shigella dysenteriae type-1 among all Shigella dysenteriae were 66.66 % in 2003, 44.44 % in 2004 and 60 % in 2005. Individual or multiple resistances to Ampicillin, Nalidixic acid, and/or Cotrimoxazole was seen in all the four species of Shigella. 33% of the total Shigella isolates reported were multi drug resistant (showing resistance to 3 or more antibiotics at a time). Shigella dysenteriae type-1(Sd 1) isolates resistant to ciprofloxacin were also encountered in the present study .Of the total 25 Shigella dysenteriae type 1 isolates reported, 18(72%) were ciprofloxacin resistant . All the Shigella isolates were however sensitive to Ceftriaxone and Azithromycin. CONCLUSION: Distribution of different species of Shigella and their antibiotic susceptibility profile may vary from one geographical location to another and may also change with time. Systematic monitoring of the species and serotypes of Shigellae and their antimicrobial susceptibility can help to guide therapy and reveal periodic epidemics due to Sd 1, which may have acquired resistance to antibiotics that have previously been effective. Key words: Dysentery, Shigella, Shigella dysenteriae type-1, Antimicrobial resistance.

[ trend of antibiotic resistance in shigellosis and the diagnostic value of erythrocyte sedimentation rate for its differentiation from viral gastroenteritides in aliasghar children hospital, Tehran [1996-2006]]

As a common infectious disease in childhood, shigellosis has a variety of seasonal and microbiologic patterns and there is a concerning trend of resistance in various parts of the world and even a single country. Inappropriate empiric therapy for any acute episode of gastroenteritis, which might be based on lab studies, could potentially lead to even further resistance. In this report, the erythrocyte sedimentation rate was studied in patients with acute gastroenteritis. Medical records of 117 patients were reviewed in this study. The mean and standard deviation of some of the acute phase inflammatory indicators were compared in two groups of shigellosis and viral gastroenteritides using independent samples t test. The mean age of the patients was 49 months, and almost half of them were male. Shigella sonnei was the commonest species isolated from these patients. Shigellosis was found to be more frequent during August to October. After 2001, resistance to ampicillin and cotrimoxazole was observed in 75% and 90% of isolates respectively. A few cases were resistant to third generation of cephalosporins [<3%]. In shigellosis, the erythrocyte sedimentation rate was significantly higher than viral gastroenteritis. Empiric use of cotrimoxazole is no longer recommended in children suspicious of contracting shigellosis in Tehran. To avoid unnecessary prescription of antibiotics for acute gastroenteritis, a normal result of erythrocyte sedimentation rate might be helpful

Current status of anti-diarrheal and anti-secretory drugs in the management of acute childhood diarrhea.

Each year 1.8 million children die due to diarrheal diseases. Indiscriminate use of antibiotics has resulted in increasing resistance to commonly used antibiotics. Moreover the recent outbreaks of shigella and cholera have revealed multi-drug resistance strains. There is a need for review of recommended antibiotics for shigellosis. From recent data it emerges that fluoroquinolones should be the first line of therapy and cephalosporins to be used as the second line. Among the anti-cholera antibiotics, tetracyclines which were the drug of choice for adults, has the advantage of high sensitivity and low cost. Single dose doxycycline would have minimal side effects, hence can be the drug of choice even in children. We should not allow the business pressures to force usage of probiotics and racecadotril as their role in the management of acute diarrhea is yet to be established. Nitazoxanide has high efficacy against Cryptosporodial diarrhea only. Strict adherence to the recommendations for the management of acute childhood diarrhea is needed or else we dilute the effect of standard management.

Shigellosis : challenges & management issues.

Infectious diseases kill about 11 million children each year while acute diarrhoeal diseases account for 3.1 million deaths in children under 5 yr of age, of which 6,00,000 deaths annually are contributed by shigellosis alone. Shigellosis, also known as acute bacillary dysentery, is characterized by the passage of loose stools mixed with blood and mucus and accompanied by fever, abdominal cramps and tenesmus. It may be associated with a number of complications of which haemolytic uraemic syndrome is the most serious. Shigellosis is caused by Shigella spp. which can be subdivided into four serogroups namely S.sonnei, S.boydii, S.flexneri and S.dysenteriae. Organisms as low as 10-100 in number can cause the disease. Shigellosis can occur in sporadic, epidemic and pandemic forms. Epidemics have been reported from Central American countries, Bangladesh, Sri Lanka, Maldives, Nepal, Bhutan, Myanmar and from the Indian subcontinent, Vellore, eastern India and Andaman and Nicobar islands. Plasmid profile of shigellae in Kolkata has shown a correlation between presence of smaller plasmids and shigellae serotypes- indicating epidemiological changes of the species. Diagnosis of shigellosis is essentially clinical. Laboratory diagnosis includes stool culture and polymerase chain reaction (PCR). Treatment includes use of an effective antibiotic, rehydration therapy (if there is dehydration) and appropriate feeding during and after an episode of shigellosis. Hand-washing is the single most important strategy for prevention of transmission of shigellosis from person to person. A safe and effective vaccine should be developed against the more important circulating strains i.e., S. dysenteriae type 1 and S. flexneri 2a.

Prevalence and pattern of antimicrobial resistance of Shigella species among patients with acute diarrhoea in Karaj, Tehran, Iran.

The study was carried out to determine the prevalence and pattern of antimicrobial resistance of Shigella species among patients with acute diarrhoea in Karaj, Tehran, Iran. The study included all acute diarrhoea patients who visited the hospitals and treatment centres of Karaj during November 2001-October 2002. Of 734 stool samples collected from patients with acute diarrhoea and analyzed for Shigella spp., 123 (16.8%) yielded Shigella spp. (7.5% Shigella flexneri, 5.2% S. sonnei, 2.6% S. dysenteriae, and 1.5% S. boydii). Of the Shigella isolates, 90.8% were resistant to one or more antimicrobial agent(s), and 87.8% were multidrug resistant. The most common resistance was to tetracycline (73.5%), trimethoprim-sulphamethoxazole (70.4%), and amoxicillin-clavulanic acid (50.0%). Resistance to cefixime, ciprofloxacin, ceftriaxone, and nalidixic acid was observed in 6.1%, 3.1%, 2.0%, and 1.0% of the isolates respectively. These findings suggest that Shigella spp. may be an important aetiological agent of diarrhoea with a high rate of drug resistance in this region, which requires further study.