Indian Journal of Medical Microbiology Medknow Publications on behalf of Indian Association of Medical Microbiology ISSN: 0255-0857 EISSN: 1998-3646 Vol. 26, Num. 1, 2008, pp. 54-57

Indian Journal of Medical Microbiology, Vol. 26, No. 1, January-March, 2008, pp. 54-57

Original Article

Role of enteric fever in ileal perforations: An overstated problem in tropics?

Capoor MR, Nair D, Chintamani MS, Khanna J, Aggarwal P, Bhatnagar D

Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi - 110 029
Correspondence Address:Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi - 110 029, deepthinair2@gmail.com

Date of Submission: 29-May-2007
Date of Acceptance: 27-Jul-2007

Code Number: mb08011

Abstract

Keywords: Enteric, ileal, management, perforations, typhoid

Enteric fever is endemic in developing countries, including India. The incidence of intestinal perforation in cases of typhoid fever is about 2-3%. ^[1] Widal test, although done routinely, has been found to be non-specific and difficult to interpret in areas where typhoid fever is endemic. ^[2] 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. ^[3],[4]

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. ^[3] 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. ^[5],[6],[7]

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]. ^[8]

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. ^[9] 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. ^[10] 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 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 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. ^[4] 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. ^[3],[4],[11] 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. ^[12]

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). ^[12] 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. ^[13] In a prior study, blood culture has been found to detectserotype Typhi in 44-83% of patients with typhoid fever; ^[2] 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. ^[14]

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. ^[15],[16] 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. ^[15]

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. ^[17] 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. ^[8]

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. ^[18] 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. ^[19] 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, ^[20] 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, ^[4] 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. ^[21],[22] 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

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