SUMMARY
The serotype distribution and susceptibility to 14 antimicrobial agents of 526 isolates of Shigella spp. from four hospitals in Sun county, Henan province, China during 2001–2008, were analysed to identify associations of serotypes with resistance trends. S. flexneri was the most frequent species (92·4%), the remainder was S. sonnei. The prevalent serotype of S. flexneri was 2a (26·7%). Almost all (>99%) isolates were resistant to tetracycline, nalidixic acid and pipemidic acid; >80% were resistant to chloramphenicol, amoxicillin and co-trimoxazole but less than 5% were resistant to polymyxin B, furazolidone, cefotaxime and gentamicin. S. flexneri showed statistically significant higher resistance than S. sonnei to amoxicillin, ampicillin, chloramphenicol and ciprofloxacin but resistance to co-trimoxazole was more common in S. sonnei than in S. flexneri. These results emphasize that monitoring of emerging resistance in Shigella isolates is essential for timely and appropriate recommendations for antimicrobial therapy.
Key words: China, epidemiology, resistance, serotypes, Shigella
INTRODUCTION
Acute dysentery caused by Shigella spp. continues to be a frequent cause of enteritis in developing countries [1–3]. In China, shigellosis is the sixth most common cause of death from infectious disease, accounting for up to 1·7 million episodes of bacillary dysentery annually, with about 200 000 patients admitted to hospitals [4, 5]. Four species are recognized, namely S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. Except for S. sonnei, each species contains multiple serotypes based on the structure of the O antigen [6]. Until recently at least 47 serotypes of all Shigella have been identified, of which 15 belong to S. flexneri [7]. In China, S. flexneri serotype 2a was the most prevalent but other serotypes such as 1a, 3a and variant X are also of major importance [8–11]. Serological typing of S. flexneri and antimicrobial resistance monitoring have long been used for the epidemiological characterization of strains. Prompt appropriate antimicrobial treatment may shorten the duration of clinical symptoms and carriage and reduce the spread of infection [12]. However, in recent years Shigella isolates have become progressively more resistant to most of the first-line drugs used [13, 14] with the outcome that tetracycline, sulfonamides, ampicillin and co-trimoxazole are no longer recommended for empirical treatment [15]. The emergence of such resistance poses a major difficulty in the choice of an appropriate antimicrobial for treatment due to shifts in the prevalence of the different serotypes and changes in the resistance patterns [16]. Knowledge of the distribution of Shigella serotypes in clinical isolates is therefore of epidemiological importance. The major objective of this study was to analyse the patterns and trends in antimicrobial resistance in Shigella isolated from a rural area of China, and to describe the distribution of Shigella serotypes associated with resistant phenotypes.
METHODS
Shigella isolates
Shigella isolates (n = 526) were recovered from 2485 faecal samples from patients with diarrhoea in four rural hospitals of Henan province, China during 2001–2008 (see Supplementary Table S1 for resistance patterns). Fresh faecal specimens were collected by swabbing mucous or blood from stool of study participants of all ages. Samples were inoculated into Cary–Blair medium and all isolates were identified according to standard microbiological and biochemical methods [17], and typed by slide agglutination test with Shigella polyvalent grouping (Mast Group Ltd, UK) and monovalent antisera (Denka Seiken Co. Ltd, Japan).
Antimicrobial susceptibility testing
Susceptibility to antimicrobial agents was determined by the disc diffusion method, as recommended by the Clinical and Laboratory Standards Institute (CLSI) [18]. The antibiotics used were cefamezin (CFZ, 30 μg), cefotaxime (CTX, 30 μg), amoxicillin (AMC, 25 μg), ampicillin (AMP, 10 μg), gentamicin (GM, 10 μg), chloramphenicol (C, 30 μg), tetracycline (TE, 30 μg), co-trimoxazole (SMZ, 25 μg), polymyxin B (PB, 300 μg), nalidixic acid (NAL, 30 μg), pipemidic acid (PI, 30 μg), ciprofloxacin (CIP, 5 μg), tobramycin (TOB, 10 μg), and furazolidone (F, 10 μg). Escherichia coli ATCC 25922 was used as the control strain for susceptibility tests. Designation of isolates as susceptible, intermediately resistant, or resistant was based on CLSI guidelines, but those showing intermediate zones of growth inhibition were interpreted as resistant.
Statistical analysis
The database software programme SPSS v. 13.0 (SPSS Inc., USA) was used for statistical analysis and all data entry was performed in duplicate. For the comparison of mean rank differences in resistance to each drug for each year with serotypes, the study (2001–2008) was divided into eight groups and serotypes into 16 groups. For non-parametric tests, the Kruskal–Wallis one-way analysis of variance was employed to compare the mean rank differences in resistance to each drug for each year and for different serotypes. A P value of <0·05 was considered statistically significant.
RESULTS
Serotypes distribution
Two Shigella spp. were identified in the 526 isolates; S. flexneri was by far the most frequent species, accounting for 92·4% with S. sonnei accounting for the remainder. Each of the 15 serotypes of S. flexneri were identified with serotypes 2a (130/486, 26·7%) and 4c (121/486, 24·9%) being the most common (Table 1). The incidence of S. sonnei fluctuated over the study period from no isolates recovered in three of the eight years to 13 isolates in 2006. The prevalent serotypes of S. flexneri also varied from 2001 to 2008 with 3a being the most frequent in 2001 (42·1%) but 2a was consistently the most common type from 2006 to 2008. Four serotypes (1c, 5, 5a, 6a) were represented by one or two isolates only (Table 1).
Table 1.
The serotype distribution of Shigella isolates during 2001–2008
| Serotype | 2001 (n = 19) | 2002 (n = 49) | 2003 (n = 144) | 2004 (n = 60) | 2005 (n = 80) | 2006 (n = 55) | 2007 (n = 56) | 2008 (n = 63) | Total (n = 526) |
|---|---|---|---|---|---|---|---|---|---|
| S. flexneri | 19 (100) | 49 (100) | 137 (95·1) | 51 (85) | 80 (100) | 42 (76·4) | 50 (89·3) | 58 (92·1) | 486 (92·4) |
| F1a | 1 (5·3) | 5 (10·2) | 8 (5·6) | 4 (6·7) | 12 (15) | 8 (14·5) | 10 (17·9) | 11 (17·5) | 59 (12·1) |
| F1b | 0 | 1 (2) | 6 (4·2) | 0 | 0 | 0 | 1 (1·8) | 0 | 8 (1·6) |
| F1c | 0 | 0 | 0 | 0 | 0 | 1 (1·8) | 0 | 0 | 1 (0·2) |
| F2a | 5 (26·3) | 15 (30·6) | 43 (29·9) | 6 (10) | 14 (17·5) | 11 (20) | 17 (30·3) | 19 (30·2) | 130 (26·7) |
| F2b | 0 | 1 (2) | 1 (0·7) | 5 (8·3) | 4 (5) | 7 (12·7) | 6 (10·7) | 6 (9·5) | 30 (6·2) |
| F2ab | 0 | 0 | 1 (0·7) | 0 | 4 (5) | 2 (3·6) | 0 | 2 (3·6) | 9 (1·9) |
| F3a | 8 (42·1) | 7 (14·3) | 0 | 0 | 0 | 0 | 0 | 0 | 15 (3·1) |
| F4 | 0 | 0 | 0 | 0 | 1 (1·3) | 2 (3·6) | 0 | 6 (5·5) | 9 (1·9) |
| F4c | 0 | 0 | 51 (35·4) | 11 (18·3) | 36 (45) | 4 (7·3) | 10 (17·9) | 9 (14·3) | 121 (24·9) |
| F5 | 0 | 2 (4·1) | 0 | 0 | 0 | 0 | 0 | 0 | 2 (0·4) |
| F5a | 0 | 1 (2) | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0·2) |
| F5b | 4 (21·1) | 14 (28·6) | 1 (0·7) | 0 | 1 (1·3) | 0 | 0 | 0 | 20 (4·1) |
| F6a | 1 (5·3) | 0 | 0 | 0 | 0 | 1 (1·8) | 0 | 0 | 2 (0·4) |
| Fx | 0 | 3 (6·1) | 16 (11·1) | 20 (33·3) | 7 (8·8) | 5 (9·1) | 5 (8·9) | 4 (6·3) | 60 (12·3) |
| Fy | 0 | 0 | 10 (6·9) | 5 (8·3) | 1 (1·3) | 1 (1·8) | 1 (1·8) | 1 (1·6) | 19 (3·9) |
| S. sonnei | 0 | 0 | 7 (4·9) | 9 (15) | 0 | 13 (23·6) | 6 (10·7) | 5 (7·9) | 40 (7·6) |
Numbers within parentheses indicate percentage in the current year.
Epidemiological characteristics
Shigella-positive patients ranged from age 2 months to 83 years (mean 18·6 years), and 54·6% were male. Infants and children from ages 0 to 10 years accounted for 55·2% of S. sonnei and 34·9% of S. flexneri cases; 20·6% of S. flexneri and 13·8% of S. sonnei isolates were from subjects aged >50 years. All isolates were recovered between May and October in the study years.
Resistant trends and profiles
Table 2 shows that >99% of all isolates were resistant to tetracycline, nalidixic acid and pipemidic acid, and >80% were resistant to chloramphenicol, amoxicillin, ampicillin and co-trimoxazole. Most isolates were susceptible to cefotaxime and gentamicin (resistance <5%), and polymyxin B and furazolidone (resistance <0·5%). Resistance to cefamezin and cefotaxime emerged in 2003, and fluctuated greatly (2·1–30·4%) in the following years. There was a significant overall decrease in resistance for amoxicillin, ampicillin, chloramphenicol and co-trimoxazole and conversely there was a significant increase in resistance to cefamezin, cefotaxime and ciprofloxacin. All isolates were resistant to two or more agents and 50 different susceptibility patterns were recorded ranging in frequency from single isolates to three patterns together accounting for 68·7% of isolates. Common resistance patterns included a combination of ampicillin, amoxicillin, chloramphenicol, tetracycline, co-trimoxazole, nalidixic acid and pipemidic acid.
Table 2.
Resistant trends of Shigella strains to different antibiotics
| Drugs | 2001 (n = 19) | 2002 (n = 49) | 2003 (n = 144) | 2004 (n = 60) | 2005 (n = 80) | 2006 (n = 55) | 2007 (n = 56) | 2008 (n = 63) | Total (n = 526) | P |
|---|---|---|---|---|---|---|---|---|---|---|
| CFZ | 0 | 0 | 3 (2·1) | 0 | 4 (5) | 3 (5·5) | 17 (30·4) | 10 (15·9) | 37 (7·0) | 0·000* |
| CTX | 0 | 0 | 3 (2·1) | 0 | 2 (2·5) | 3 (5·5) | 5 (8·9) | 5 (7·9) | 18 (3·4) | 0·024* |
| AMC | 18 (94·7) | 45 (91·8) | 133 (92·4) | 51 (85) | 76 (95) | 41 (74·5) | 48 (85·7) | 57 (90·5) | 469 (89·2) | 0·017† |
| AMP | 18 (94·7) | 46 (93·9) | 133 (92·4) | 51 (85) | 80 (100) | 41 (74·5) | 51 (91·1) | 62 (98·4) | 482 (91·6) | 0·000† |
| GM | 0 | 2 (4·1) | 3 (2·1) | 0 | 8 (10) | 1 (1·8) | 6 (10·7) | 4 (6·3) | 24 (4·6) | n.s. |
| TOB | 1 (5·3) | 2 (4·1) | 3 (2·1) | 4 (6·7) | 12 (15) | 2 (3·6) | 3 (5·4) | 11 (17·5) | 38 (7·2) | n.s. |
| C | 19 (100) | 48 (98) | 134 (93·1) | 51 (85) | 80 (100) | 55 (100) | 48 (85·7) | 57 (90·5) | 492 (93·5) | 0·000† |
| TE | 19 (100) | 48 (98) | 144 (100) | 59 (98·3) | 79 (98·8) | 55 (100) | 54 (96·4) | 63 (100) | 521 (99·0) | n.s. |
| SMZ | 19 (100) | 40 (81·6) | 130 (90·3) | 47 (78·3) | 65 (81·3) | 45 (81·8) | 34 (60·7) | 42 (66·7) | 422 (80·2) | 0·000† |
| PB | 0 | 0 | 1 (0·7) | 0 | 0 | 0 | 0 | 0 | 1 (0·2) | n.s. |
| NAL | 18 (95) | 49 (100) | 144 (100) | 60 (100) | 80 (100) | 55 (100) | 56 (100) | 63 (100) | 525 (99·8) | n.s. |
| PI | 18 (95) | 49 (100) | 144 (100) | 60 (100) | 80 (100) | 55 (100) | 56 (100) | 63 (100) | 525 (99·8) | n.s. |
| CIP | 0 | 2 (4·1) | 16 (11·1) | 19 (31·7) | 28 (35) | 16 (29·1) | 22 (39·3) | 36 (57·1) | 139 (26·4) | 0·000* |
| F | 0 | 0 | 0 | 0 | 1 (1·3) | 0 | 0 | 0 | 1 (0·2) | n.s. |
AMP, Ampicillin; AMC, amoxicillin; C, chloramphenicol; CFZ, cefamezin; CIP, ciprofloxacin; CTX, cefotaxime; F, furazolidone; GM, gentamicin; NAL, nalidixic acid; PB, polymyxin B; PI, pipemidic acid; SMZ, co-trimoxazole; TE, tetracycline; TOB, tobramycin.
n, Total number of strains; n.s., not significant.
Numbers within parentheses indicate percentage.
Statistically significant increase mean rank in resistance to the antibiotic in question during the years of comparison.
Significantly decreasing.
The percentages of S. flexneri and S. sonnei resistant to antibiotics are given in Table 3. The proportion of isolates with resistance to specific drugs varied by species. S. flexneri showed higher resistance than S. sonnei to amoxicillin (96·1% vs. 2·5%, P < 0·05), ampicillin (97·1% vs. 25%, P < 0·05), chloramphenicol (97·5% vs. 20·0%, P < 0·05), and ciprofloxacin (21·8% vs. 5·0%, P < 0·05), but resistance to co-trimoxazole, cefamezin, and gentamicin was more common in S. sonnei than S. flexneri isolates. Overall S. flexneri serotype 1b strains compared to other serotypes showed the least resistance to ampicillin, amoxicillin, chloramphenicol, nalidixic acid and pipemidic acid; one isolate only of variant Y showed resistance to polymyxin B and furazolidone.
Table 3.
The resistant phenotypes of Shigella serotypes
| Drugs | Serotype | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F1a (n = 59) | F1b (n = 8) | F1c (n = 1) | F2a (n = 130) | F2b (n = 30) | F2ab (n = 9) | F3a (n = 15) | F4 (n = 9) | F4c (n = 121) | F5 (n = 2) | F5a (n = 1) | F5b (n = 20) | F6 (n = 2) | Fx (n = 60) | Fy (n = 19) | Flexneri (n = 486) | Sonnei (n = 40) | P | |
| CFZ | 4 (6·8) | 1 (12·5) | 0 | 9 (6·9) | 4 (13·3) | 1 (11·1) | 1 (6·7) | 0 | 5 (3·8) | 0 | 0 | 1 (5) | 0 | 2 (3·3) | 2 (10·5) | 30 (6·2) | 7 (17·5) | 0·007 |
| CTX | 2 (3·4) | 0 | 0 | 5 (3·8) | 3 (10) | 1 (11·1) | 0 | 0 | 2 (1·5) | 0 | 0 | 0 | 0 | 1 (1·6) | 1 (5·3) | 15 (3·1) | 2 (5) | n.s. |
| AMC | 57 (96·6) | 4 (50) | 1 (100) | 127 (97·7) | 30 (100) | 8 (88·8) | 14 (93·3) | 9 (100) | 118 (97·7) | 2 (100) | 1 (100) | 17 (85) | 2 (100) | 60 (100) | 18 (94·7) | 468 (96·1) | 1 (2·5) | 0·000 |
| AMP | 57 (96·6) | 4 (50) | 1 (100) | 127 (97·7) | 30 (100) | 9 (100) | 14 (93·3) | 9 (100) | 120 (99·2) | 2 (100) | 1 (100) | 20 (100) | 2 (100) | 58 (96·7) | 18 (94·7) | 472 (97·1) | 10 (25) | 0·000 |
| GM | 2 (3·4) | 0 | 0 | 4 (3·1) | 0 | 0 | 0 | 0 | 4 (3) | 0 | 0 | 0 | 0 | 2 (3·3) | 0 | 12 (2·4) | 12 (30) | 0·000 |
| C | 57 (96·6) | 7 (87·5) | 1 (100) | 125 (96·2) | 30 (100) | 9 (100) | 15 (100) | 9 (100) | 118 (97·7) | 2 (100) | 1 (100) | 20 (100) | 2 (100) | 60 (100) | 18 (94·7) | 474 (97·5) | 8 (20) | 0·000 |
| TE | 59 (100) | 8 (100) | 1 (100) | 128 (98·5) | 30 (100) | 9 (100) | 15 (100) | 9 (100) | 121 (100) | 2 (100) | 1 (100) | 20 (100) | 2 (100) | 58 (96·7) | 19 (100) | 482 (99·2) | 39 (97·5) | n.s. |
| SMZ | 41 (69·5) | 4 (50) | 0 | 100 (77) | 21 (70·0) | 7 (77·8) | 13 (86·7) | 5 (55·5) | 108 (89·3) | 1 (50) | 1 (100) | 15 (75) | 2 (100) | 42 (70) | 14 (73·7) | 374 (77·0) | 39 (97·5) | 0·002 |
| PB | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (5·3) | 1 (0·2) | 0 | n.s. |
| NAL | 57 (96·6) | 7 (87·5) | 1 (100) | 126 (97) | 30 (100) | 9 (100) | 15 (100) | 9 (100) | 118 (97·7) | 2 (100) | 1 (100) | 20 (100) | 2 (100) | 60 (100) | 18 (94·7) | 475 (97·7) | 40 (100) | n.s. |
| PI | 57 (96·6) | 7 (87·5) | 1 (100) | 126 (97) | 30 (100) | 9 (100) | 15 (100) | 9 (100) | 118 (97·7) | 2 (100) | 1 (100) | 20 (100) | 2 (100) | 60 (100) | 18 (94·7) | 475 (97·7) | 40 (100) | n.s. |
| CIP | 21 (35·6) | 1 (12·5) | 0 | 64 (49·2) | 8 (26·7) | 1 (11·1) | 0 | 2 (22·2) | 22 (18·3) | 0 | 0 | 0 | 0 | 13 (21·7) | 3 (15·8) | 135 (27·8) | 2 (5) | 0·002 |
| F | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (5·3) | 1 (0·2) | 0 | n.s. |
| TOB | 5 (8·5) | 1 (12·5) | 0 | 9 (6·9) | 4 (13·3) | 1 (11·1) | 1 (6·7) | 0 | 9 (7·6) | 0 | 0 | 1 (5) | 0 | 4 (6·7) | 1 (5·3) | 36 (7·4) | 2 (5) | n.s. |
AMP, Ampicillin; AMC, amoxicillin; C, chloramphenicol; CFZ, cefamezin; CIP, ciprofloxacin; CTX, cefotaxime; F, furazolidone; GM, gentamicin; NAL, nalidixic acid; PB, polymyxin B; PI, pipemidic acid; SMZ, co-trimoxazole; TE, tetracycline; TOB, tobramycin.
n, Total number of strains; n.s., not significant.
Numbers within parentheses indicate percentage.
DISCUSSION
The distribution of Shigella spp. appears to vary with geographical region. For example, a national survey in the USA reported that 80% of more than 1500 isolates were S. sonnei with 18% S. flexneri; S. boydii and S. dysenteriae together accounted for <2% of isolates [19]. However, in developing countries such as in sub-Saharan Africa [20], S. flexneri often predominates and surveys report frequencies of 73% in Peru [21] and >60% in Kolkata, India [22]. These differences are most likely associated with socio-economic factors, geography, and population density. The predominance of S. flexneri 2a has also been reported elsewhere [23, 24]. In the present study, this serotype along with 4c and variant X ranked in the top three most common S. flexneri serotypes during the period 2001–2008 and serotype 2a has remained dominant since 2006. Five serotypes of S. flexneri were detected at the start of the survey in 2001 and eight in 2008. The fluctuation of serotypes over the survey may explain the high incidence of dysentery in the study area but social and public health factors cannot be discounted. Nevertheless, these changes in serotype prevalence underscore the importance of surveillance monitoring as part of public health strategies for reducing the incidence of shigellosis and, moreover, provide important data relevant to vaccine development.
The development of resistance to antimicrobial drugs by Shigella necessitates a continuous surveillance programme. It is clear from the study that treatment of infections caused by S. flexneri in this province of China was compromised by widespread resistance to ampicillin, amoxicillin, chloramphenicol and tetracycline, the drugs most widely used for treatment of shigellosis. Resistance to these drugs remained high and relatively steady over the survey period, with only minor fluctuations. It may be possible to reverse this trend of resistance as was achieved in Israel where an almost complete ban on the use of chloramphenicol for the treatment of shigellosis brought about a steady decrease in the number of Shigella strains resistant to this drug, reaching almost zero with a concomitant increase in susceptibility [25]. Our study indicated that resistance of Shigella isolates to cefamezin, cefotaxime and ciprofloxacin is increasing significantly, as in the USA [26], and multidrug resistance is common. Recently, third-generation cephalosporin resistance in Shigella isolates has rapidly emerged in India and in parts of China [27, 28] and this is most likely due to overuse of these agents in healthcare and other sectors such as agriculture owing to a lack of legislative guidelines limiting their use [11]. On the other hand, our data suggest that cephalosporins still have a place along with polymyxin B for the treatment of shigellosis in this region of China, but the finding of ceftriaxone-resistant strains of S. flexneri early in the survey as well as reports from Shenyang in 2000 and in France in 1995 [29, 30] suggest that cephalosporins should be used with caution.
The data show that the resistant phenotypes were also serotype-specific. Overall, S. flexneri was more frequently resistant to ampicillin, amoxicillin, chloramphenicol and ciprofloxacin, alone or in combination, than S. sonnei. A possible explanation is that S. sonnei infections are clinically less severe than S. flexneri, and most cases would not receive antimicrobial therapy thus negating the selective pressure from antibiotic therapy as shown by several other studies [10, 31–33]. Interestingly, resistance to co-trimoxazole was more common in S. sonnei than S. flexneri isolates but the reason for this is unknown. However, a major limitation of comparing the susceptibilities of the two species is the great discrepancy between the number of isolates of each species; 12 times more isolates of S. flexneri than S. sonnei were examined. Severe gastroenteritis, some of which is due to Shigella, is often treated empirically with ciprofloxacin especially in the community. As a consequence the finding of more than one-quarter of S. flexneri isolates to be resistant to ciprofloxacin compromises its empirical use for treatment of shigellosis [13, 22]. Therefore, treatment for severe shigellosis, especially in children and the immunosuppressed, must be guided by continued surveillance data of emerging resistance in Shigella isolates and these data should inform timely and appropriate recommendations for antimicrobial therapy.
Supplementary Material
Supplementary information supplied by authors.
ACKNOWLEDGEMENTS
The Center for Disease Control and Prevention of Henan province supported this study. We thank Malika Humphries and Julie King for help with the English text.
Supplementary material
For supplementary material accompanying this paper visit https://doi.org/10.1017/S0950268812002543.
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DECLARATION OF INTEREST
None.
REFERENCES
- 1.Hou F, et al. Trends of antibiotic resistance in strains of Shigella isolated in Beijing over 8 years. Journal of Chinese Pharmaceutical Sciences 2002; 11: 51–54. [Google Scholar]
- 2.Megan ER, et al. A large, multiple-restaurant outbreak of infection with Shigella flexneri serotype 2a traced to tomatoes. Clinical Infectious Diseases 2006; 42: 163–169. [DOI] [PubMed] [Google Scholar]
- 3.Opintan J, Newman MJ. Distribution of serogroups and serotypes of multiple drug resistant Shigella isolates. Ghana Medical Journal 2007; 41: 8–29. [PMC free article] [PubMed] [Google Scholar]
- 4.Wang X Y, et al. Trend and disease burden of bacillary dysentery in China (1991–2000). Bulletin of the World Health Organization 2006;84: 561–568. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Huang ZJ, et al. Analysis on the character of the death because of infection disease in the disease surveillance 2000, China. Disease Surveillance 2002; 17: 265–266. [Google Scholar]
- 6.Simmons DA, Romanowska E. Structure and biology of Shigella flexneri O antigens. Journal of Medical Microbiology 1987; 23: 289–302. [DOI] [PubMed] [Google Scholar]
- 7.WHO. Generic protocol to estimate the burden of Shigella diarrheal and dysenteric mortality (www.who.int/gpv-documents/). Geneva: World Health Organization, 1999. [Google Scholar]
- 8.Qu F, et al. Distribution and antimicrobial resistance of Shigella isolates isolated from diarrhea patients between 1993 and 2002 in Beijing. Chinese Journal of Antibiotics 2004; 29: 671–674. [Google Scholar]
- 9.Li H, Huan JX, Long J. Analysis of serotypes and resistance of Shigella isolates. International Medicine & Health Guidance News 2007; 13: 67–70. [Google Scholar]
- 10.Yu HL, et al. Analysis on the status of Shigella isolates. Antimicrobial resistance though data from the National Shigellosis Surveillance System in China in 2005. Chinese Journal of Epidemiology 2007; 28: 370–373. [PubMed] [Google Scholar]
- 11.Xia S, et al. Prevalence and characterization of human Shigella infections in Henan Province, China, in 2006. Journal of Clinical Microbiology 2011; 49: 232–242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Salam MA, Bennish ML. Antimicrobial therapy for shigellosis. Reviews of Infectious Diseases 1991; 13: 332–341. [DOI] [PubMed] [Google Scholar]
- 13.Haukka K, Siitonen A. Emerging resistance to newer antimicrobial agents among Shigella isolated from Finnish foreign travelers. Epidemiology and Infection 2007; 20: 1–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.El-Gendy AM, et al. Genetic diversity and antibiotic resistance in Shigella dysenteriae and Shigella boydii strains isolated from children aged <5 years in Egypt. Epidemiology and Infection 2012;2: 229–230. [DOI] [PubMed] [Google Scholar]
- 15.Niyogi SK. Shigellosis. Journal of Microbiology 2005;43: 133–143. [PubMed] [Google Scholar]
- 16.Kotloff KL, et al. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bulletin of the World Health Organization 1999; 77: 651–666. [PMC free article] [PubMed] [Google Scholar]
- 17.WHO. Programme for control of diarrhoeal disease. In Manual for Laboratory Investigation of Acute Enteric Infections, CDD/83.3, Rev. 1. Geneva: World Health Organization, 1987. [Google Scholar]
- 18.CLSI. Performance standards for antimicrobial susceptibility testing; approved standard, 14th edn, document M100-S14. Wayne, PA: Clinical and Laboratory Standards Institute, 2004. [Google Scholar]
- 19.Sivapalasingam S, et al. High prevalence of antimicrobial resistance among Shigella isolates in the United States tested by the National Antimicrobial Resistance Monitoring System from 1999 to 2002. Antimicrobial Agents and Chemotherapy 2006; 50: 49–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Ram PK, et al. Analysis of data gaps pertaining to Shigella infections in low and medium human development index countries, 1984–2005. Epidemiology and Infection 2007; 136: 577–603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Fernandez PM, et al. Molecular epidemiology of Shigella flexneri in a diarrhea-endemic area of Lima, Peru. Epidemiology and Infection 2004; 132: 303–316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Pazhani GP, et al. Species diversity and antimicrobial resistance of Shigella spp. isolated between 2001 and 2004 from hospitalized children with diarrhea in Kolkata (Calcutta), India. Epidemiology and Infection 2005; 133: 1089–1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Vasilev V, et al. Variability of Shigella flexneri serotypes in Israel during a period of two years: 2000 and 2001. Epidemiology and Infection 2004; 132: 51–56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Khan AI, et al. Shigella serotypes among hospitalized patients in urban Bangladesh and their antimicrobial resistance. Epidemiology and Infection 2004; 132: 773– 777. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Mates A, Eyny D, Philo S. Antimicrobial resistance trends in Shigella serogroups isolated in Israel, 1990–1995. European Journal of Clinical Microbiology & Infectious Diseases 2000; 19: 108–111. [DOI] [PubMed] [Google Scholar]
- 26.Folster JP, et al. Decreased susceptibility to ciprofloxacin among Shigella isolates in the United States, 2006 to 2009. Antimicrobial Agents and Chemotherapy 2011; 55: 1758–1760. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Bhattacharya D, et al. Rapid emergence of third-generation cephalosporin resistance in Shigella spp. isolated in Andaman and Nicobar Islands, India. Microbial Drug Resistance 2011; 17: 329–332. [DOI] [PubMed] [Google Scholar]
- 28.Qiu S, et al. Emergence of resistance to fluoroquinolones and third-generation cephalosporins in Shigella flexneri subserotype 1c isolates from China. Clinical Microbiology and Infection 2012; 18: 95–98. [DOI] [PubMed] [Google Scholar]
- 29.Chen J, et al. Analysis on the distribution and resistance of Shigella serotypes during the three years in Shen Yang. Occupation and Health 2002; 18: 38–41. [Google Scholar]
- 30.Fortineau N, et al. SHV-type extended-spectrum beta-lactamase in a Shigella flexneri clinical isolate. Journal of Antimicrobial Chemotherapy 2001; 47: 685–688. [DOI] [PubMed] [Google Scholar]
- 31.Jos B, et al. Antimicrobial resistance and serotypes of Shigella isolates in Kigali, Rwanda (1983 to 1993): increasing frequency of multiple resistance. Diagnostic Microbiology and Infectious Disease 1997; 28: 165–171. [DOI] [PubMed] [Google Scholar]
- 32.Gu B, et al. Comparison of the prevalence and changing resistance to nalidixic acid and ciprofloxacin of Shigella between Europe-America and Asia-Africa from 1998 to 2009. International Journal of Antimicrobial Agents. Published online: 4 April 2012. doi: 10.1016/j.ijantimicag.2012.02.005. [DOI] [PubMed] [Google Scholar]
- 33.Zhang W, et al. Wide dissemination of multidrug-resistant Shigella isolates in China. Journal of Antimicrobial Chemotherapy 2011; 66: 2527–2535. [DOI] [PubMed] [Google Scholar]
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