|Year : 2008 | Volume
| Issue : 1 | Page : 54-57
Role of enteric fever in ileal perforations: An overstated problem in tropics?
MR Capoor1, D Nair1, MS Chintamani2, J Khanna2, P Aggarwal1, D Bhatnagar2
1 Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi - 110 029, India
2 Department of Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi - 110 029, India
|Date of Submission||29-May-2007|
|Date of Acceptance||27-Jul-2007|
Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Purpose: To determine the role of enteric fever in ileal perforations. Methods: A prospective cohort of 47 patients of ileal perforation was subjected to clinical examination and investigations for APACHE II scoring. Blood, ulcer edge biopsy, mesenteric lymph node and peritoneal aspirate were subjected to culture to determine the predominant aerobic bacterial isolate and its antibiogram. Results: Seven patients (14.9%) required intensive care and seven (14.9%) developed septicaemia. Mortality was 17%. Highest isolation rate was seen in ulcer edge (70.2%) followed by lymph node (66%) culture. The bacterial spectrum was Escherichia coli (23.4%), Enterococcus faecalis (21.3%), Salmonella enterica serovar Typhi (6.3%), Salmonella enterica serovar Paratyphi A (4.2%), etc. Conclusions: Enteric fever organisms are not the predominant causative agents of ileal perforations. Culture of ulcer edge biopsy, lymph node is crucial for aetiological diagnosis. The use of APACHE II triaging and prescription of antimicrobials based on the local pattern of susceptibility profile of the aetiological agent is recommended.
Keywords: Enteric, ileal, management, perforations, typhoid
|How to cite this article:|
Capoor M R, Nair D, Chintamani M S, Khanna J, Aggarwal P, Bhatnagar D. Role of enteric fever in ileal perforations: An overstated problem in tropics?. Indian J Med Microbiol 2008;26:54-7
|How to cite this URL:|
Capoor M R, Nair D, Chintamani M S, Khanna J, Aggarwal P, Bhatnagar D. Role of enteric fever in ileal perforations: An overstated problem in tropics?. Indian J Med Microbiol [serial online] 2008 [cited 2019 Oct 18];26:54-7. Available from: http://www.ijmm.org/text.asp?2008/26/1/54/38859
Enteric fever is endemic in developing countries, including India. The incidence of intestinal perforation in cases of typhoid fever is about 2-3%.  Widal test, although done routinely, has been found to be non-specific and difficult to interpret in areas where typhoid fever is endemic.  Diagnosis of typhoid is rarely confirmed and in the majority of cases of enteric perforation, only a conjectural diagnosis is based on the circumstantial evidence of terminal ileal, antimesenteric perforation in an adult running fever for two weeks. In India, typhoid is seen in 8-50% cases of gastrointestinal perforation. There is paucity of information from India on aetiology, morbidity and mortality in this regard. ,
The proximal intestinal perforations are more common in India as compared to the distal intestinal perforations, which are more frequent in developed countries. Site and aetiological factors of perforations also show geographical variations.  Therefore, there is a need to study this problem, especially in a typhoid-endemic country like India, where the burden of ileal perforations is high and there is convincing evidence that surgical intervention and definitive antibiotic therapy can decrease mortality. ,,
This study was undertaken to determine the aetiological diagnosis, appropriate therapeutic approach of ileal perforation and to re-visit the concept of 'enteric perforation'.
| ~ Materials and Methods|| |
The present study was conducted in a 1570-bed tertiary care centre in North India. A prospective cohort of 47 patients of ileal perforations was included in the study from July 2003 to July 2004. All patients underwent a thorough clinical examination and relevant investigations for APACHE II scoring. Blood for culture was collected prior to initiation of antibiotics. Pre-operative resuscitation included intravenous fluids, intravenous antibiotics and correction of electrolyte derangement etc., as indicated. Adequate urine output, normal serum electrolytes and urea were included as indicators of adequate resuscitation. Based on the APACHE II scorings, patients were triaged into three management groups [Table - 1]. 
Exploratory laparotomy was performed in all patients after adequate resuscitation, by a midline incision. The operative findings were recorded and the amount of pus and faecal material were estimated and drained after collecting a sample for culture. Edge of the perforation was excised and sent to microbiology laboratory in normal saline. A draining mesenteric lymph node (LN) was also excised and transported in normal saline for culture. Peritoneal aspirate (5-10 mL) from around the ulcer was aspirated. Based on APACHE II triaging, appropriate surgery was performed. The peritoneal cavity was lavaged thoroughly with 2-3 L of normal saline.  Drains were placed in the right paracolic gutter and the pelvic cavity.
Patients less than 12 years of age, those with gastric, duodenal, appendicular or colonic perforations and those who died before resuscitation and surgery were excluded from the study.
All samples were processed as per standard procedures. Blood cultures were processed by automation (BacT alert 3D system, bioMιrieux, France) to hasten culture recovery. The biopsy specimens (ulcer edge and draining LN) and peritoneal fluid were cultured in brain heart infusion-based blood agar, McConkey Agar for pyogenic and MB/BacT bottles (bioMιrieux, France) for Mycobacterium tuberculosis culture. For LN culture, core culture was performed. Organisms isolated from the blood or LN were considered clinically significant. If blood and lymph node culture was sterile, culture from ulcer edge biopsy was considered of probable significance. Isolates cultured only from peritoneal fluid were considered of doubtful significance.
Isolates were identified based on cultural characteristics, biochemical reactions and serotyping, wherever indicated.
Antimicrobial susceptibility of the isolates was performed on Mueller Hinton agar by Kirby Bauer disk diffusion method as per NCCLS 2004 guidelines.  For Gram negative isolates, ampicillin (10 μg), cotrimoxazole (1.25/23.75 μg), nalidixic acid (30 μg), ciprofloxacin (5 μg), ofloxacin (5 μg), cefixime (5 μg), ceftriaxone (30 μg), cefuroxime (30 μg), amikacin (30 μg), cefoperezone/sulbactum (70/30 μg), meropenem (10 μg), piperacillin/tazobactam (100/10 μg) disks were used. For gram positive isolates, penicillin (10 U), oxacillin (1 μg), erythromycin (15 μg), gentamicin (10 μg), ciprofloxacin (5 μg), vancomycin (30 mg), teicoplanin (30 mg), clindamycin (2 mg) disks were used. For Enterococcus faecalis , high-level gentamicin (120 μg) was used along with other aforementioned antimicrobials for Gram positive organisms.
Based on the sensitivity of the isolates, the antibiotics were changed if required.
| ~ Results|| |
There were 36 (76.6%) males and 11 (23.4%) females. Their age ranged from 13 to 46 years with a mean age of 27.3 years (±6.72 years). Most of the patients presented with a short duration of fever with mean of 6.67 days (±2.58 days, range 4-16 days). Seven patients (14.9%) required ICU admission in the post-operative period. Seven patients (14.9%) developed septicaemia and eight (17%) patients died. The outcome was compared between three APACHE II groups as detailed in [Table - 2]. APACHE II Group III patients had lower duration of fever, higher mortality and morbidity, and frequently required ICU care.
Blood culture was positive in 13 (27.7%) patients. Ulcer edge was positive in 33 (70.2%) patients. Lymph node culture was positive in 31 (66%) patients. Peritoneal fluids grew organism in 57.4%, but contaminants were seen in 20 (42.5%) patients. The contaminants included Diphtheroids , aerobic spore bearer and Micrococci . The bacterial spectrum in enteric perforations was Escherichia More Details coli 11 (23.4%), Enterococcus faecalis 10 (21.3%), Klebsiella pneumoniae 7 (14.9%), Citrobacter freundii 7 (14.9%), Enterobacter spp. 3 (6.3%), Salmonella More Details enterica serovar Typhi 3 (6.3%), Staphylococcus aureus 3 (6.3%), Salmonella enterica serovar Paratyphi A 2 (4.2%), Acinetobacter and alpha- haemolytic Streptococci in 2 (4.2%) patients each. Histopathological examination of the ulcer edge biopsy revealed ulcer edge with loss of intestinal epithelium and surrounded by acute inflammatory response. All the biopsies were negative for Mycobacterium tuberculosis culture.
The antibiotic susceptibility pattern of the isolates is depicted in [Table - 3],[Table - 4].
| ~ Discussion|| |
The mortality rate from ileal perforations remains high in developing countries, despite improvement in critical care and timely surgical intervention.  This is attributed to delayed presentation of the patient owing to inappropriate prescription, over-the-counter availability of antimicrobials and poor infection control practices.
Patients in this series were young adult and males. Similar findings were also seen in prior reports. ,, These occurred most frequently during the early 2 nd or even the 1 st week of illness, but not in the 3 rd week as has been previously described. 
In this study Group III, patients of APACHE II triaging had lower duration of fever, higher mortality and morbidity and frequently required ICU care. This was also corroborated by previous reports; however, the duration of fever was longer (>14 days).  Lower duration of fever reflects a more virulent infection from the onset.
In the current study, the highest isolation rate was seen from the ulcer edge (70.2%) followed by lymph node (66%) culture. A previous study found the highest rate of isolation from LN despite prior antimicrobial treatment. The bacteria in these sites are less affected by antibiotic treatment than in blood, despite the considerably higher volume of blood sample. All the more, this is useful as many patients in the developing countries are treated with antibiotics before presenting to the hospital. In our study, the blood culture was positive in 27.7% patients only. Furthermore, the incidence of enteric fever isolates was less (10.5%). This is attributed to the fact that the isolation of enteric fever isolates from blood and bone marrow is difficult in patients suffering from gut perforations than with other complications.  In a prior study, blood culture has been found to detectserotype Typhi in 44-83% of patients with typhoid fever;  however, the number of organisms, stage of the disease, type of culture medium used, incubation period and presence of inhibitors in blood, limit its positivity. Moreover, in an endemic area, high prevalence of antibody titres and anamnestic response seen on any febrile illness limit the usefulness of widal test. 
Escherichia coli (23.4%) was the predominant isolate in our study as compared to enteric fever organisms (10.5%). Similar findings were corroborated by previous studies. , Although the reports of ileal perforations are many, studies showing aetiological diagnosis confirmed by culture of blood sample or lymph node aspirate or ulcer edge or peritoneal fluid are scarce. 
The APACHE II score is of value in predicting outcome and in stratification of patients with intra-abdominal infection as it is independently associated with the rate of mortality. Therefore, it was adopted by Surgical Infection Society as the best available method of risk stratification in intra-abdominal infections.  Our own experience in using APACHE II triaging to decide the modality of surgery especially in performing ileostomy in the majority of Group II and Group III patients and comparing the outcomes with other units in our institute had shown significant reduction in mortality in Group II patients. 
The intra-abdominal infections are caused by endogenous bacteria of gut. The small bowel shows 10 3 to 10 4 CFU/mL of organisms, with a change in composition of flora near the ileocaecal valve. In the distal ileum, gram negative organisms dominate gram positive species, with aerobic gram negative organisms consistently present along with anaerobic bacteria.  Although E. coli and Bacillus fragilis are considered the most significant intra-abdominal pathogens, the data indicates that this is true of only lower GI spillage.  For community-acquired infections, perforations beyond proximal ileum are caused by anaerobic organism. Therefore, keeping this in mind, anaerobic culture was not done in the current study and in patients who were initiated on metronidazole to avoid post-operative anaerobic infections. Tuberculosis was also ruled out by acute presentation of patients and by histopathological and culture examination.
As per the guidelines of the Infectious Disease Society of America and the Surgical Infection Society 2003,  therapy depends on whether intra-abdominal infections are community acquired or nosocomial. For patients with community-acquired infections of mild to moderate severity, agents with narrow spectrum of activity, such as cefuroxime plus metronidazole or quinolones plus metronidazole are preferable. Patients with severe infects may benefit from regimens with broad-spectrum antimicrobials like combination drugs or carbapenems or extended spectrum cephalosporins plus metronidazole. Nosocomial infections include more resistant organisms. For these infections, complex multidrug regimens are recommended. In this series, the empirical antibiotics were prescribed as per the aforementioned guidelines and were changed as per sensitivity pattern.
The mortality rate of 17.7% in the current series is slightly higher than other studies,  as the majority of patients had a APACHE II and III score requiring resection anastomosis with illeostomy, resuscitation or ICU care.
This study provides reappraisal into the microbiology and pathology of enteric perforation. It underscores the need for ulcer edge biopsy and lymph node culture for aetiological diagnosis. It may be inferred that even in a typhoid-endemic country like India, the ileal perforations behave like secondary peritonitis of any other aetiology. , Since ileal perforations are the most common surgical emergencies managed by a resident trainee in India, we recommend the use of APACHE II triaging and prescription of antimicrobials based on the local pattern of susceptibility profile and not empirical use of antityphoid drugs.
| ~ References|| |
|1.||Meier DE, Imediegwu OO, Tarpley JL. Perforated typhoid enteritis: Operative experience with 108 cases. Am J Surg 1989;157:423-7. |
|2.||Chaudhary R, Shanker S, Nisar N, Dey AB. Recent advances in the diagnosis of enteric fever. Trop Gastroenterol 1995;16:8-12. |
|3.||Agarwal S, Gera N. Tuberculosis: An underestimated cause of ileal perforation. J Indian Med Assoc 1996;94:341-52. |
|4.||Jhobta RS, Attri AK, Kaushik R, Sharma R, Jhobta A. Spectrum of perforation peritonitis in India: Review of 504 consecutive cases. World J Emerg Surg 2006;1:26. |
|5.||Mosdell DM, Morris DM, Voltura A. Antibiotic treatment for surgical peritonitis. Ann Surg 1991;214:543-9. |
|6.||Falagas ME, Barefoot L, Griffith J, Ruthazar R, Snydman DR. Risk factors leading to clinical failure in the treatment of intra-abdominal of skin/soft tissue infection. Eur J Ciln Microbiol Infect Dis 1996;15:913-21. |
|7.||Basten JPV, Stockenbrugger R. Typhoid perforation: A review of literature since 1960. Trop Geogr Med 1994;46:336-9. |
|8.||Chintamani MS, Borah C, Krishna SV, Mishra A, Bhatnagar D, et al . APACHE-II triaging in the optimum management of small bowel perforations. Trop Doctor 2001;31:198-201. |
|9.||Bosscha K, Van Vroonhoven Th. JMV, Van der Werken Ch. Surgical management of severe secondary peritonitis. Br J Surg 1999;86:1371-7. |
|10.||CLSI. Performance standards for antimicrobial susceptibility testing, CLSI Document Wayne PA, CLSI. 2004 (M100-516, 16 th Informational supplement). |
|11.||Sharma L, Gupta S, Soni AS, Sikora SS, Kapoor V. Generalized peritonitis in India: The Tropical spectrum. Jpn J Surg 1991;21:272-7. |
|12.||Christie AB. Infectious diseases: Epidemiology and clinical practice. 3 rd ed. Churchill Livingstone: Edinburgh; 1980. p. 80. |
|13.||Wain J, Bay PV, Vinh H, Duong NM, Diep TS, Walsh AL, et al . Quantitation of bacteria in bone marrow from patients with typhoid fever: Relationship between counts and clinical features. J Clin Microbiol 2001;39:1571-6. |
|14.||Levine MM, Grados O, Gilman RH, Woodwards WE, Solis-Plaza R, Waldman W. Diagnostic value of the widal test in areas endemic for typhoid fever. Am J Trop Med Hyg 1978;27:795-800. |
|15.||Bhansali SK. Gastrointestinal perforations: A Clinical study of 96 cases. J Postgrad Med 1967;13:1-12. |
|16.||Brook I. Microbiology and management of intra-abdominal infection in children. Pediatr Int 2003;45:123-9. |
|17.||Nystom PO, Bax R, Dellinger EP, Dominioni L, Knaus WA, Meakins JL. Proposed definitions for diagnosis, severity scoring, stratification and outcome for trials on intra-abdominal infection: Joint Working Party of SIS North America and Europe. World J Surg 1990;14:148-58. |
|18.||Simon GL, Gorbach SL. The human intestinal microflora. Dig Dis Sci 1986;31:147s-62s. |
|19.||Walker AP, Krepel CJ, Gohr CM, Edmiston CE. Microflora of abdominal sepsis: Locus of infection. J Clin Microbiol 1994;32:557-8. |
|20.||Solomkin JS, Mazuski JE, Baron EJ, Sawyer RG, Nathens AB, DiPiro JP. Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis 2003;37:997-1005. |
|21.||Lawrence KR, Adra M, Schwaitzberg SD. An overview of the pathophysiology and treatment of secondary peritonitis. Formulary 2003;38:102-11. |
|22.||Montravers P, Gauzit R, Muller C. Emergence of antibiotic resistant bacteria in cases of peritonitis after intra-abdominal surgery affects the efficacy of empirical antibiotic therapy. Clin Infect Dis 1996;23:486-94. |
[Table - 1], [Table - 2], [Table - 3], [Table - 4]
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