Occurrence of shigellosis in the young and elderly in rural China: results of a 12-month population-based surveillance study

In 2002, population- and treatment center-based surveillance was used to study the disease burden of shigellosis in rural Hebei Province in the People's Republic of China. A total of 10,105 children with diarrhea or dysentery were enrolled. Infants were treated most frequently for diarrhea (1,388/1,000/year) followed by children < or = 5 years old (618/1,000/year). Shigellosis was treated most often in children 3-4 years old (32/1,000/year) and people > 60 years of age (7/1,000/year). Fifty-six percent (184 of 331) Shigella isolates were detected in patients who had non-bloody diarrhea. Shigella flexneri was identified in 93% of 306 isolates. The most common S. flexneri serotypes were 1a (34%), X (33%), and 2a (28%). More than 90% of the Shigella isolates were resistant to cotrimoxazole and nalidixic acid, but remained susceptible to ciprofloxacin, norfloxacin, and gentamicin. Widespread resistance to antibiotics adds urgency to the development and use of vaccines to control shigellosis.     

Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam

Shigellosis is an important cause of infectious diarrhea in Vietnam, caused mainly by Shigella flexneri. This study provides for the first time in the international literature, data on the development of antimicrobial resistance in Shigella between 1988 to 1998, including data reported to the National Program for Surveillance of Antimicrobial Resistance (NPSAR). Our studies show that about 80% of the Shigella strains tested were resistant to ampicillin, chloramphenicol, oxytetracycline, trimethoprim and sulfonamides. This combination of drugs was also the most common antibiogram among multiple-resistant S. flexneri (57%). Resistance to tetracyclines, sulfonamides and, in particular trimethoprim (p<0.001), increased during the study period. Our findings indicate that tetracyclines and co-trimoxazole (a combination of a sulfonamide and trimethoprim), which are recommended and commonly used drugs for the treatment of shigellosis in Vietnam, may have limited therapeutic effect. In contrast to neighboring countries, low percentages of resistance were found to nalidixic acid and norfloxacin (3-5%) and no resistance was found to ciprofloxacin, indicating that nalidixic acid with its low cost and safety in children could be recommended for the treatment of shigellosis. The NPSAR provides a useful picture of the levels and development of antimicrobial resistance in Vietnam and should receive continued support for further improvement by increasing the number of provinces covered, the numbers of isolates tested from rural areas, and the communication of results to medical practitioners and others prescribing and/or selling antimicrobials.     

Emergence of antimicrobial-resistant shigellosis in Oregon.

Ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) are currently considered acceptable empirical therapy for shigellosis in developed countries. However, there are few recently reported studies on antimicrobial resistance among shigellae isolated in the United States. We examined the epidemiology of shigellosis and the antimicrobial susceptibility of Shigella species isolated in Oregon from July 1995 through June 1998. Of 430 isolates, 410 were identified to the species level: Shigella sonnei accounted for 55% of isolates, and Shigella flexneri, for 40%. The overall annual incidence of shigellosis was 4.4 cases per 100,000 population. Children aged <5 years (annual incidence, 19.6 cases per 100,000 population) and Hispanics (annual incidence, 28.4 cases per 100,000 population) were at highest risk. Of 369 isolates tested, 59% were resistant to TMP-SMZ, 63% were resistant to ampicillin, 1% were resistant to cefixime, and 0.3% were resistant to nalidixic acid; none of the isolates were resistant to ciprofloxacin. Thirteen percent of the isolates had multidrug resistance to ampicillin, chloramphenicol, streptomycin, sulfisoxazole, and tetracycline. Infections due to multidrug-resistant shigellae are endemic in Oregon. Neither ampicillin nor TMP-SMZ should be considered appropriate empirical therapy for shigellosis any longer; when antibiotics are indicated, a quinolone or cefixime should be used.     

Comparison of norfloxacin versus nalidixic acid in therapy of acute urinary tract infections

Thirty-seven adult patients with acute urinary tract infections (UTI) were randomized to receive either a seven day (lower UTI) or a 14 day (upper UTI) course of norfloxacin 400 mg orally twice daily, or nalidixic acid 1 g orally four times per day. Mean age, underlying disease and infecting organisms were similar in the two groups. Nine patients in the norfloxacin group and seven in the nalidixic acid group had presumptive evidence of upper UTI. Overall, 12 patients had antibody-coated bacteria-positive infections. The infecting organisms were: Escherichia coli (27), coagulase-negative staphylococci (four), Citrobacter freundii (three), Klebsiella pneumoniae (three), and Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Enterobacter agglomerans, Streptococcus agalactiae, Enterococcus faecalis (one of each). All of the organisms were susceptible to norfloxacin, while 81% were susceptible to nalidixic acid. The effects on the periurethral and anal canal flora were similar in both groups. Five patients in each group experienced adverse clinical effects. The cure rates for norfloxacin and nalidixic acid were 79 and 83%, respectively. There were two failures, two relapses and four reinfections in the norfloxacin group. In the nalidixic acid group, there were two failures, one relapse and four reinfections. One of the failure patients in the nalidixic acid group developed resistance to the drug, and two of the four reinfections were due to organisms resistant to nalidixic acid. In this patient population it was concluded that nalidixic acid may be as effective as norfloxacin in the treatment of acute, symptomatic UTI.     

Isolation of Shigella species and their resistance patterns to a panel of fifteen antibiotics in mid and far western region of Nepal

ObjectiveTo determine the antimicrobial resistance patterns of Shigella species to the most commonly used antibiotics in mid and far western part of Nepal.MethodsStool samples were collected from 458 patients who came from mid and far western region of Nepal, attending OPD & IPD Departments of Nepalgunj Medical College, Nepal, between the periods of September 2011 to March 2013. Standard microbiological procedures were used for isolation and identification of Shigella species while the disc diffusion test was used to determine the antimicrobial resistance patterns of the recovered isolates.ResultsA total of 65 isolates were identified as Shigella species. Shigella flexneri, Shigella dysenteriae, Shigella boydii and Shigella sonnei were accounted respectively for 43.07%, 27.69%, 21.53% and 7.69% of the total number of Shigella isolated. Resistances to nalidixic acid (95.38%), ampicillin (84.62%), co-trimoxazole (81.54%) and ciprofloxacin (46.15%) were observed. Greater number of isolates (38.46%) was recovered from those aged 1-10 years. This was statistically significant (P<0.05), compared to the other age groups.ConclusionsThe study revealed the endemicity of shigellosis with Shigella flexneri as the predominant serogroup. Children were at a higher risk of severe shigellosis. The results also suggest that nalidixic acid, ampicillin, co-trimoxazole and ciprofloxacin should not be used empirically as the first line drugs in the treatment of shigellosis. Periodic analysis of resistance patterns is necessary for the appropriate selection of empirical antimicrobial therapy.     

Surveillance for antimicrobial resistance profiles among Shigella species isolated from a semirural community in the northern administrative area of santiago, chile

Variations in antibiotic resistance patterns were studied among 178 Shigella strains isolated from 1997 to 2001 in children less than five years of age with acute diarrhea from Colina, a semi-rural community in Santiago, Chile. The minimal inhibitory concentration of several commonly used antibiotics was determined by the agar dilution method. Shigella strains showed high rates of resistance to ampicillin (82%), cotrimoxazole (65%), tetracycline (53%), and chloramphenicol (49%). Furthermore, 51% of the strains showed resistance patterns to multiple antibiotics. Only 9% of the strains were resistant to amoxicillin-clavulanic acid and no resistance was observed to ciprofloxacin, nalidixic acid, or cefotaxime. Continuous monitoring of resistance patterns in Shigella is essential for establishing and updating guidelines for antibiotic treatment in shigellosis.     

Incidence of bacterial enteropathogens among hospitalized diarrhea patients from Orissa, India

Bacteriological analysis of 1,551 stool/rectal swabs from all age groups of diarrhea patients of different hospitals of Orissa from January 2004 to December 2006 was carried out using standard procedures. Among all enteropathogens isolated in 886 culture-positive samples, Escherichia coli constituted 75.5%, including 13.2% pathogenic E. coli; Vibrio cholerae O1 constituted 17.3%; V. cholerae O139, 1%; Shigella spp., 4.5% (Shigella flexneri type 6, 2.9%, S. dysenteriae type I, 0.7%, S. sonnei, 0.6%, and S. boydii, 0.3%); Salmonella spp., 0.7%; and Aeromonas spp., only 2.0%. The isolation of bacterial enteropathogens was highest during July, 2005, followed by September, 2006. The prevalence of shigellosis in this region was relatively low. Cholera cases were more frequent during the rainy seasons. The dominance of V. cholerae O1 Inaba over Ogawa serotypes was observed in 2005, whereas this trend was reversed in 2006. The resistance profile of V. cholerae O1 was co-trimoxazole (Co), furazolidone (Fr), and nalidixic acid (Na); for Aeromonas spp., it was ampicillin (A), Fr, ciprofloxacin (Cf), Na, norfloxacin (Nx), and Co. Pathogenic E. coli strains were resistant to A, Fr, Co, streptomycin (S), Cf, Na, Nx, and neomycin (N); Shigella spp. were resistant to Fr, Na, Co, and S; and Salmonella spp. were resistant to A and Fr. Active surveillance should be continued among diarrhea patients to look for different enteropathogens and to define the shifting antibiogram patterns in this region.     

Analysis of fecal leukocytes and erythrocytes in Shigella infections in urban Bangladesh

We evaluated the usefulness of enumeration of fecal leukocytes and erythrocytes in making an early diagnosis of Shigella infection, where Shigella is a leading cause of invasive diarrhea. Stool specimens from 561 invasive diarrhea patients were submitted for microscopic examination. A presumptive diagnosis of shigellosis based on microscopic examination was made in 389 of them; 227 had stool cultures positive for Shigella spp (Shigella patients). One hundred sixty-two patients with no detectable Shigella infection (non-Shigella invasive diarrhea cases) served as a comparison group. Two hundred twenty-seven randomly selected Shigella patients and 227 non-Shigella infectious diarrhea cases from the surveillance system database of the hospital constituted another group for comparative evaluation. The stool specimens of the patients were examined under the microscope, and isolation, biochemical characterization and serotyping of Shigella were performed. In comparison with non-Shigella invasive diarrhea cases, the presence of >50 WBC/hpf in association with any number of RBC in the fecal sample had a modest sensitivity of 67%, specificity of 59%, positive predictive value of 70%, negative predictive value of 56%, accuracy of 64%, and positive likelihood ratio of 1.6 in predicting shigellosis. Comparison between Shigella and non-Shigella infectious diarrhea patients revealed the presence of >20 WBC/hpf was a less accurate predictor of shigellosis (sensitivity 51%, specificity 88%, positive predictive value 81%, negative predictive value 64%, accuracy 69%, and positive likelihood ratio 4.1). Direct microscopical examination of stool specimens for the presence of WBC and RBC may facilitate the early diagnosis of shigellosis, and may be a cheap alternative to stool culture in this setting.     

Antimicrobial resistance of Shigella isolates in Bangladesh, 1983-1990: increasing frequency of strains multiply resistant to ampicillin, trimethoprim-sulfamethoxazole, and nalidixic acid.

The susceptibility to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) was determined for 15,824 isolates of Shigella obtained from patients attending a treatment center in Dhaka, Bangladesh, from 1983 through 1990 and for 520 isolates obtained during community surveys from 1988 through 1990. Susceptibility to nalidixic acid was determined for isolates obtained after 1985. In 1983 13% of isolates were resistant to ampicillin, 23.5% to TMP-SMZ, and 0.8% to both drugs. By 1990 51.2% of isolates obtained at the Diarrhea Treatment Centre were resistant to ampicillin, 47.7% to TMP-SMZ, and 40.5% to both drugs (for comparison with figures for 1983, P less than .001). Resistance to nalidixic acid increased from 0.8% in 1986 to 20.2% in 1990 (P less than .001). In 1990 71.5% of Shigella dysenteriae type 1 isolates were resistant to ampicillin, 68.5% to TMP-SMZ, 67.7% to both drugs, and 57.9% to nalidixic acid. The resistance pattern of isolates obtained during community surveillance was similar to that of Treatment Centre isolates. In Bangladesh ampicillin and TMP-SMZ are no longer useful for treatment of infection with any species of Shigella, and nalidixic acid is no longer useful for treatment of infections due to S. dysenteriae type 1.     

Antimicrobial resistance of Shigella isolates in the USA: the importance of international travelers

A nationwide sample of Shigella isolates was collected and tested for resistance to 12 antimicrobial agents to assess the prevalence and epidemiologic correlates of antimicrobial resistance in Shigella. Of the isolates, 32% were resistant to ampicillin, 7% to trimethoprim-sulfamethoxazole, and 0.4% to nalidixic acid. Fifty (20%) of 252 isolates were associated with foreign travel. The best predictor of clinically important resistance was a history of foreign travel: 20% of isolates from foreign travelers showed trimethoprim-sulfamethoxazole resistance, compared with only 4% of isolates from those without such a history. Quinolone resistance was not identified in travel-related isolates, and quinolones may be more appropriate for initial therapy of travel-related shigellosis than is trimethoprim-sulfamethoxazole.     

Antimicrobial use in children under five years with diarrhea in a central region province, Thailand

This cross-sectional study aimed to estimate the prevalence of appropriate antimicrobial prescribing for treating childhood diarrhea within the public hospital system in a central region province, Thailand. Reported are findings of a prospective clinical audit of 424 cases treated by 38 physicians. Appropriate use of antimicrobials was defined as prescribing antimicrobials for managing an invasive bacterial-type, bloody diarrhea or not prescribing antimicrobials for managing a watery-type or non-bloody diarrhea. Among 424 cases with diarrhea, 12.5% were invasive bacterial-type. Of the 66 diarrheal episodes in which stool samples were cultured, 7 stool specimens were positive, two with Shigella sonnei, two with Vibrio cholerae Ogawa and three with E. coli. Based on the presence of mucus and blood in stools, 27.4% of 424 cases received appropriate antimicrobial drugs. Cotrimoxazole was the most commonly prescribed drug (51%), followed by colistin sulfate (15.3%), norfloxacin (11%), and nalidixic acid (0.5%). The average number of antimicrobials per case of inpatients was higher than outpatients (1.15 vs 0.84, p < 0.001). There was a trend toward prescribing norfloxacin in childhood diarrhea. The Ministry of Public Health should continue providing effective interventions aimed at improving physicians' knowledge of diarrhea treatment. Similar efforts should be directed toward improving caretakers' knowledge about home care for childhood diarrhea and encouraging widespread correct use of oral rehydration therapy (ORT) in the community. Hopefully, such activities will help reduce the inappropriate use of antimicrobial agents in treating diarrheal disease.     

Presumptive shigellosis: clinical and laboratory characteristics of Bangladeshi patients

The aim of the study was to examine some selected clinical and laboratory parameters in distinguishing non-Shigella invasive diarrhoeas from culture-confirmed Shigella cases. We conducted a clinic-based, cross-sectional study at the Dhaka Hospital of ICDDR,B located in Bangladesh. In total, 389 patients of all age groups and of both genders, with a history of diarrhoea of less than 96 h and presence of visible blood and/or mucus in the stool were presumed to have shigellosis and enrolled in the study. Shigella was isolated from faecal cultures in 227 (58.4%) patients. The remaining 162 (41.6%) patients did not have Shigella isolated from their faecal cultures and constituted the comparison group. Another 238 randomly selected patients with non-Shigella diarrhoea from the Diarrhoeal Disease Surveillance System database of the Dhaka Hospital constituted another comparison group. Cases of culture-proven Shigella were similar to non-Shigella invasive diarrhoeal patients with presumptive shigellosis with regard to several biosocial variables. The nutritional status of children with shigellosis was significantly inferior to those with non-Shigella diarrhoea. The presence of macrophages more than 5/HPF in stool microscopic examination was significantly more frequent among patients infected with Shigella. Empirical antimicrobial therapy for shigellosis might be considered for malnourished diarrhoeal children presenting with history of visible blood and/or mucus in stool, and children older than 1 y of age. Further studies are needed in different geographical settings to identify clinical and laboratory parameters that could help identify patients with shigellosis.     

In vitro selection of Escherichia coli mutants with decreased susceptibility to norfloxacin

In 10 clinical isolates of Escherichia coli the frequency of spontaneous mutation to high levels of resistance to nalidixic acid was greater than 300-fold higher than that to norfloxacin. Norfloxacin resistant mutants could not be detected (mutation frequency: less than 10(-12). However, nalidixic acid resistant mutants of E. coli developed decreased susceptibility to norfloxacin at a rate of approximately 10(-9). Mutants with decreased susceptibility to norfloxacin could also be obtained when the same clinical isolates of E. coli were exposed to norfloxacin in 2 steps. However, mutants with MIC values greater than 8 micrograms/ml for norfloxacin were never obtained even after repeated exposure. Widespread use of cinoxacin or nalidixic acid may select resistant strains and reduce the efficacy of norfloxacin and other 4-quinolones.     

Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled study. Swedish Study Group.

OBJECTIVE: To evaluate the clinical and microbiologic efficacy and safety of norfloxacin for acute diarrhea. DESIGN: Double-blind, placebo-controlled, randomized clinical multicenter trial. SETTING: Six departments of infectious disease. PARTICIPANTS: Patients 12 years of age or older with a history of acute diarrhea lasting 5 or fewer days. Eighty-five percent of patients (511/598) were evaluable for efficacy. Of these evaluable patients, 70% had traveled abroad within the previous 6 weeks. INTERVENTIONS: Patients received either norfloxacin, 400 mg, or placebo twice daily for 5 days. MEASUREMENTS: Enteric pathogens were isolated in 51% of the evaluable patients: Campylobacter species in 29%, Salmonella species in 16%, Shigella species in 3.5%, and other pathogens in 2.6%. RESULTS: Norfloxacin had a favorable overall effect compared with placebo (cure rate, 63% compared with 51%; P = 0.003). There were statistically favorable effects in culture-positive patients, patients with salmonellosis, and severely ill patients but not in culture-negative patients or patients with campylobacteriosis or shigellosis. A significant difference was noted between norfloxacin and placebo in median time to cure among all evaluable patients (3 compared with 4 days, P = 0.02) and in patients with campylobacteriosis (3 compared with 5 days, P = 0.05) but not in patients. Culture-positive, but not culture-negative patients, in the norfloxacin group had significantly fewer loose stools per day compared with patients in the placebo group from day 2 onward (P less than or equal to 0.01). Norfloxacin was significantly less effective than placebo in eliminating Salmonella species on days 12 to 17 (18% compared with 49%, P = 0.006), whereas the opposite was true for Campylobacter species (70% compared with 50%, P = 0.03). In six of nine patients tested, norfloxacin-resistant Campylobacter species (MIC, greater than or equal to 32 micrograms/mL) appeared after norfloxacin treatment. CONCLUSION: Empiric treatment reduced the intensity and, to some extent, the duration of symptoms of acute diarrhea. The effect was restricted to patients who had bacterial enteropathogens or who were severely ill. The clinical usefulness of this treatment is limited by the fact that norfloxacin seems to delay the elimination of salmonella and to induce resistance in campylobacter.     

Comparison of the efficacy of ceftibuten and norfloxacin in the treatment of acute gastrointestinal infection in children

A prospective randomized study was conducted at an infectious disease hospital in Thailand. Ceftibuten was compared with norfloxacin, both given orally for five days for treatment of acute gastroenteritis in children. One hundred and seventy cases were included in the study. Eighty-eight cases were treated with ceftibuten and eighty-two cases with norfloxacin. The baseline characteristics of the patients in both treatment groups were similar. The results showed that mean durations of diarrhea in the ceftibuten and norfloxacin groups were 2.48 days and 2.29 days, respectively, but there was no statistically significant difference between the two groups (p > 0.05). There were Salmonella spp and Shigella spp isolated in both treatment groups and all were susceptible to both antibiotics. The mean durations of Salmonella diarrhea in the ceftibuten and norfloxacin groups were 2.7 and 2.2 days, respectively, while those of Shigella diarrhea were 2.3 days and 2.0 days, respectively. There were no statistically significant differences in either comparison (p > 0.05). Neither complications nor clinical relapses were observed after both antibiotics' treatment.     

C reactive protein and prealbumin as markers of disease activity in shigellosis.

To evaluate serum C reactive protein (CRP) and prealbumin concentrations as markers of disease activity in shigellosis this study serially measured serum concentrations of CRP and prealbumin in 39 patients infected with Shigella spp, and a comparison group of 10 patients infected with Vibrio cholerae serotype 01. On admission, patients with shigellosis had significantly higher median concentrations of CRP (109 v 5 mg/l; p < 0.01) and significantly lower median concentrations of prealbumin (16 v 23 mg/l; p < 0.01) than did patient with cholera. Among Shigella spp infected patients, CRP concentrations were significantly lower, and prealbumin concentrations significantly higher, on study days 3 and 5 when compared with admission values. Among Shigella spp infected patients, those in whom treatment failed had higher admission CRP concentrations than those in whom treatment was successful (p = 0.142). An admission CRP concentration > or = 110 mg/l had a 70% sensitivity and a 61% specificity in predicting failure of treatment among patients infected with Shigella spp; the predictive value of a positive and negative test was 14% and 96% respectively. In summary, acute shigellosis elicits an acute phase response, the magnitude of which predicts clinical outcome.     

Hemolytic uremic syndrome associated with shigellosis: report of two cases

Two patients with hemolytic uremic syndrome admitted to Udornthani Hospital, Thailand, were reported. The preceding illness was shigellosis. The stool culture was positive for Shigella dysenteriae in one patient and Shigella flexneri in another. The management was successful with peritoneal dialysis in one and symptomatic treatment in another. Both patients had complete recovery.     

The relative importance of Shigella in the aetiology of childhood gastroenteritis in Saudi Arabia.

The role of shigella infection in childhood gastroenteritis was studied over a 2-year period. Shigella species were found in the faecal specimens of 70 (1%) of 7369 children with gastroenteritis, but in only 1 (0.1%) of 1130 controls. S. flexneri was the commonest isolate (51%), followed by S. sonnei (37%). Most shigella species were isolated during the winter. The prevalence of shigellosis was highest for children 1-5 years of age but equal for both sexes. Fever, abdominal cramps, vomiting, and bloody diarrhoea were the predominant clinical features. Of the shigella isolates, 73% were resistant to cotrimoxazole, 43% to ampicillin, and 41% to chloramphenicol. One-third of isolates were resistant to greater than or equal to 3 antibiotics. All isolates were susceptible to nalidixic acid. The illness was mild and self-limiting and most patients recovered without antimicrobial therapy.     

Urine bactericidal activity of pefloxacin versus norfloxacin in healthy female volunteers after a single 800-mg oral dose

Summary In an open randomised crossover study the antibacterial activity of pefloxacin and norfloxacin was assessed in the urine after a single 800-mg oral dose in 14 healthy female volunteers. Pefloxacin demonstrated lower peak concentrations in the urine than norfloxacin (mean, 217.2 mg/l versus 492.9 mg/l as determined by the microbiological assay) but pefloxacin was present over a longer period of time in sufficient concentrations than norfloxacin. Mean urine levels of at least 2 mg/l were present for 7 days after pefloxacin administration and 2 days after norfloxacin administration as determined by the microbiological assay. Overall, the urinary recovery of pefloxacin and norfloxacin amounted to 49.3% and 25.1%, respectively, of the total administered dose. The average urine bactericidal activity against the five test organisms was as follows: against reference strainEscherichia coli ATCC 25922 susceptible to nalidixic acid (Nal-S) for 5 days with pefloxacin and 2 days with norfloxacin; against three clinical isolates, one strain each ofE. coli resistant to nalidixic acid (Nal-R),Klebsiella pneumoniae Nal-R, andStaphylococcus saprophyticus, for 3 days with pefloxacin and 24 h with norfloxacin; and against a clinical isolate ofEnterococcus faecalis for 2 days with pefloxacin and 12 h with norfloxacin. In conclusion, pefloxacin as a single dose proved to have sufficiently high and long-lasting urine bactericidal activity against urinary pathogens. These findings support the results of a meta-analysis of seven clinical trials in patients with uncomplicated lower UTI, demonstrating a single oral dose of 800 mg pefloxacin to be as effective as a conventional treatment with comparative drugs [21].