- Email: [email protected]
Confirmation of meningococcal disease by urinary antigen testing
CONCISE COMMUNICATIONS
Confirmation of meningococcal disease by urinary antigen testing S. C. Clarke, J. Reid, L. Thom and G. F. S. Edwards Scottish Meningococcus and Pneumococcus Reference Laboratory, House on the Hill, Stobhill Hospital, Glasgow G21 3UW, UK
Tel/Fax: þ44 141201 3836
E-mail: [email protected]
The meningococcus is an important cause of morbidity and mortality and a rapid laboratory diagnosis is required through accurate, non-culture-based methods. Body fluids that are easily obtainable are preferred for this route of diagnosis and urine is the specimen of choice as it can be obtained non-invasively. Urine samples were tested from patients with suspected meningococcal disease and tested by latex agglutination and PCR. It was shown that urinary PCR is not useful for the laboratory confirmation of MD but latex agglutination testing may be useful in certain settings prior to confirmatory testing by a reference laboratory. Keywords Urine, meningococci, antigen, polymerase chain reaction Accepted 3 July 2001
The meningococcus is one of the main causes of meningitis, particularly in countries where conjugate vaccines against Haemophilus influenzae type b disease have been introduced, and is an important cause of morbidity and mortality [1,2]. The search for new therapeutic and diagnostic methods therefore continues, with the aims of reducing the morbidity and mortality associated with meningococcal disease (MD), and performing effective surveillance of the disease. Although polysaccharide vaccines have been available for the prevention of a number of serogroups of MD, these vaccines have generally had a short duration of protection and could not be used in young children. New conjugate vaccines are now available for the prevention of serogroup C MD [3,4], but there are no conjugate vaccines yet available for the prevention of other invasive meningococcal serogroups. As technology improves, new methods are becoming available for the laboratory confirmation of MD. These include PCR and DNA sequencing methods [5,6]. Automation is also becoming increasingly used as it becomes affordable [7]. However, most of these methods are limited to specialised laboratories and therefore result in reporting delays. To enable a rapid diagnosis of MD to be made local diagnostic microbiology laboratories require access to quick but accurate methods [8]. Owing to the common use of antibiotics prior to hospital admission [9], non-culture confirmation of disease is important, although every effort should be made to gain a culture confirmation. Methods are therefore required that can provide a rapid, accurate and non-culture diagnostic route to confirm a clinical suspicion of MD. Body fluids that are easily obtainable are preferred for this route of diagnosis, and urine is the specimen of choice, because it can usually be obtained non-invasively. As all PCR requests for the laboratory confirmation of MD in Scotland are forwarded to the Scottish Meningococcus and Pneumococcus Reference Laboratory (SMPRL), and there is a delay
due to postal and testing time, testing for urinary antigen would be a rapid and cost-effective screening method for MD in a local diagnostic laboratory. Urines that are positive by latex agglutination could then be forwarded to the reference laboratory for further testing. Two preliminary studies have been performed for the rapid detection of meningococcal antigen in urine [10,11], but the number of samples used was small. Here we describe the usefulness of latex agglutination and PCR testing on unconcentrated and concentrated urine for the laboratory confirmation of MD. A request was made to all diagnostic microbiology laboratories throughout Scotland to send urine samples from patients suspected of having MD. Urines were taken at the onset of illness and sent to the SMPRL for testing. All testing was performed on unconcentrated and concentrated urine. Unconcentrated urine was boiled for 5 min Concentration of urine was initially performed with 5 mL, using the commercially available Millipore Minicon B15 concentration system (Amicon, Millipore, Watford, UK), according to the manufacturer’s instructions. However, this was found to result in inhibition of the PCR reaction, and was therefore replaced with the Vivapore 5 (Sartorius, Epsom, Surrey, UK), a similar method that could be used for comparison. After concentration, the urine was again boiled for 5 min Unconcentrated and concentrated urines were tested for the presence of meningococcal antigen using the Wellcogen latex agglutination test (Abbot Diagnostics, Maidenhead, UK). Urines that were positive for serogroups A, C, Yand W135 by latex agglutination were tested further by coagglutination to determine the individual serogroup [12]. Unconcentrated and concentrated urines were also tested for the presence of meningococcal antigen, using PCR to detect the insertion element IS1106, as previously described [13,14]. Between August 1999 and July 2000, a total of 133 urines were received from 128 patients and tested for the presence of
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases
566 Clinical Microbiology and Infection, Volume 7 Number 10, October 2001
Table 1 Positive results from antigen testing of unconcentrated and concentrated urine by latex agglutination and PCR
Urine
Latex serogroup
Unconcentrated PCR
Concentrated PCR
1 2 3 4 5 6 7 8 9
B B B B C C B C Negative
Negative Negative Negative Negative Negative Negative Negative Negative Negative
Negative Negative Inhibitor present Negative Inhibitor present Negative Negative Negative Positive
meningococcal antigen as described. The first 59 urines were tested by the Millipore Minicon B15 method, and eight urines were positive for meningococcal antigen by latex agglutination, as previously reported [11]. Five of these were serogroup B, and three were serogroup C. The remaining 51 urines were negative by latex agglutination. Only one urine of these 51 was positive by PCR after concentration (urine 9, Table 1), and it had been negative by latex agglutination. Further testing on this patient by a meningococcal outer membrane protein (OMP) serum antibody ELISA method suggested that the patient did not have MD. PCR inhibition factors were present in eight (14%) unconcentrated urines and 19 (32%) concentrated urines. Owing to the high number of urines possessing these inhibition factors after concentration using the Millipore system, the concentration technique was replaced with the Vivapore 5 system. A further 74 urines were tested by latex agglutination and PCR. No urines were positive by either latex agglutination or PCR when unconcentrated or concentrated samples were used. Inhibition factors were again common, being found in 37 (50%) of samples. Summarised results are shown in Table 2. Antigen detection tests are routinely used by the SMPRL and can provide sensitive and specific methods for the confirmation of MD [6]. Blood or cerebrospinal fluid are the samples routinely used for antigen detection, because urine has never been evaluated for its usefulness. However, it is well known that latex agglutination tests, although highly sensitive, often produce false positives, particularly in the presence of proteins normally found in urine [15]. Latex agglutination could be used as a screening assay, followed by the PCR test as a more sensitive and specific assay, with the possibility of confirming the Table 2 PCR inhibition information using two commercially available concentration systems Commercial system
Unconcentrated
Concentrated
Minicon B15 Vivapore 15
8 (16%) 15 (20%)
19 (37%) 37 (50%)
serogroup of infection using the siaD PCR method [16]. In this study, 133 urine samples from 128 patients with suspected MD were analyzed. Concentration of the urine did not affect the latex agglutination result. Three of the latex agglutinationpositive urines were confirmed by other methods, while the other five were not confirmed, either because other tests were negative or because no other samples were received. Latex agglutination of urine for the confirmation of MD may therefore be useful as an urgent measure for confirming and obtaining the serogroup of the infecting meningococcus in local diagnostic laboratories where PCR testing is not available. Further testing and confirmation may then be achieved at a reference laboratory, where other tests using samples other than urine, such as whole blood or cerebrospinal fluid, may be used. The urinary PCR test was not useful for the laboratory confirmation of MD. All but one of the urines tested were negative for the insertion element IS1106, using both unconcentrated and concentrated urine. The concentrated urine that was positive by PCR was not confirmed by other methods and may have been a false-positive result. The concentration of urine using either commercial system increased the number of urines that exhibited factors resulting in inhibition of the PCR reaction. These factors may cause such inhibition by reducing the amount of available magnesium ions in the PCR reaction mix [17]. Although this can be counteracted by increasing the magnesium ion concentration, the variability in the amount of inhibitor may result in a less rigid PCR assay for clinical diagnostic use. Normally, the IS1106 PCR assay is very useful for the laboratory confirmation of MD using other body fluids, such as whole blood or cerebrospinal fluid [6]. Although falsepositive results using this gene target have been reported [18], this was generally not a problem in this study. True positives can often be confirmed by other slightly less sensitive PCR assays that detect the ctrA and siaD genes, respectively [5,16], although this was not the case for this positive.
R EFER E NCE S 1. Achtman M. Global epidemiology of meningococcal disease. Meningococcal Dis 1995; 7: 159–75. 2. Noah N, Henderson B. Surveillance of bacterial meningitis in Europe 1997/98. London: Public Health Laboratory Service, 1998. 3. Chief Medical Officer. Introduction of immunisation against group C meningococcal infection. PAL51979. Health Department, Scotland, 1999. 4. Chief Medical Officer. Start of the New Meningococcal C Conjugate Vaccine Immunisation Programme. PL/CMO/99/4. London: Department of Health, England and Wales, 1999. 5. Guiver M, Borrow R, Marsh J et al. Evaluation of the Applied Biosystems automated Taqman polymerase chain reaction system for the detection of meningococcal DNA. FEMS Immunol Med Microbiol 2000; 28: 173–9. 6. Clarke SC, Edwards GFS. Guidance for requests and interpretation of services provided by the Scottish Meningococcus and
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Concise Communications
7.
8.
9. 10.
11. 12.
Pneumococcus Reference Laboratory. SCIEH Weekly Rep 2000; 34: 228–32. Clarke SC, Diggle MA, Reid JA, Thom L, Edwards GFS. Introduction of an automated service for the laboratory confirmation of meningococcal disease in Scotland. J Clin Pathol 2001; 54: 556–7. Gray SJ, Sobanski MA, Kaczmarksi EB et al. Ultrasound-enhanced latex immunoagglutination and PCR as complementary methods for non-culture-based confirmation of meningococcal disease. J Clin Microbiol 1999; 37: 1797–801. Cartwright K, Reilly S, White D, Stuart J. Early treatment with parenteral penicillin in meningococcal disease. Br Med J 1992; 305: 484. al-Wali W, Hughes C. Urine antigen detection can be quicker than PCR in the diagnosis of meningococcal disease. J Hosp Infect 1998; 40: 326–8. Clarke SC. Urinary antigen diagnosis of meningococcal disease. Br J Biomed Sci 2000; 57: 153–5. Eldridge J, Sutcliffe EM, Abbott JD, Jones DM. Serological grouping of meningococci and detection of antigen in cerebrospinal fluid by coagglutination. Med Lab Sci 1978; 35: 63–6.
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13. Ni H, Knight AI, Cartwright K, Palmer WH, McFadden J. Polymerase chain reaction for diagnosis of meningococcal meningitis. Lancet 1992; 340: 1432–4. 14. Newcombe J, Cartwright K, Palmer WH, McFadden J. PCR of peripheral blood for diagnosis of meningococcal disease. J Clin Microbiol 1996; 34(7): 1637–40. 15. Weinberg GA, Storch GA. Preparation of urine samples for use in commercial latex agglutination tests for bacterial antigens. J Clin Microbiol 1985; 21: 899–901. 16. Borrow R, Claus H, Guiver M et al. Non-culture diagnosis and serogroup determination of meningococcal B and C infection by a sialyltransferase (SiaD) PCR ELISA. Epidemiol Infect 1997; 118: 111–17. 17. Abu Al-Soud W, Ra˚dstro¨ m P. Purification and characterization of PCR-inhibitory components in blood cells. J Clin Microbiol 2001; 39: 485–93. 18. Borrow R, Guiver M, Sadler F et al. False positive diagnosis of meningococcal infection by the IS1106 PCR ELISA. FEMS Microbiol Lett 1998; 162: 215–18.
Pyogenic hepatic abscess: clues for diagnosis in the emergency room J. L. Herna´ndez and C. Ramos Department of Internal Medicine, Hospital Marque´ s de Valdecilla, Santander, Spain E-mail: [email protected] The objective of this paper is to describe the clinical and diagnostic characteristics of patients with pyogenic hepatic abscesses evaluated in the emergency room, and to know whether it is feasible to make an early diagnosis based on any of these characteristics. The setting was an urban, tertiary-care teaching hospital. This was a retrospective study of 63 adult patients admitted to our institution because of pyogenic liver abscesses from January 1991 to December 1998. Keywords Liver abscess, emergency care, diagnosis Accepted 8 June 2001
Clin Microbiol Infect 2001: 7: 567–570 IN T R ODUC T ION Pyogenic hepatic abscess (PHA) represents an infrequent and sometimes life-threatening entity [1]. Its recognition has clearly improved in the last decade through the development of more sensitive and specific imaging techniques, such as ultrasonography (US) and computed tomography (CT), with their relevant therapeutic implications [2,3]. Standard treatment protocols usually recommend a combination of drainage and antimicrobial therapy, although no specific antibiotic schemes have been defined due to the lack of large, prospective studies [4]. Diagnosing PHA in an initial stage remains a difficult task today, frequently due to the paucity of the presenting symptoms Corresponding author and reprint requests: Jose´ Luis Herna´ ndez, Department of Internal Medicine, Hospital Marque´ s de Valdecilla, University of Cantabria, 39008 Santander, Spain E-mail: [email protected]
or the radiological features. However, several studies have confirmed that an early diagnosis is associated with improved survival [5–7]. This study will describe the clinical and diagnostic characteristics of patients with PHA evaluated at a first-step hospital level, the emergency room (ER). PAT IE N T S AND ME T HOD S The medical records of all adult patients admitted between January 1991 and December 1998 at the Marque´ s de Valdecilla University Hospital, and discharged with a diagnosis of PHA, were reviewed. This is an 1100-bed tertiary-care center that serves as the reference hospital for a population of 500 000, and as the first-level hospital for an area including about 350 000 inhabitants in Northern Spain. Therefore, this population can be regarded as an unselected sample of this entity in our area.
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568 Clinical Microbiology and Infection, Volume 7 Number 10, October 2001
Data were obtained by a retrospective review of clinical charts of patients with PHA, selected through the computerised database of the Admissions and Clinical Documentation Department. PHA was defined on the evidence of one or more liver collections without radiological characteristics of malignancy, in US or CT studies, along with the identification of pus or bacteria, either microscopically or by culture [5]. For the purposes of the study, patients were divided into two different groups. Those patients in whom a diagnosis of PHA was reached in the ER, constituted group A. Group B contained those patients in whom PHA was not detected in the ER evaluation. The median follow-up of patients was 12 months. Data on recurrence and mortality were also collected. PHA-related mortality included both mortality resulting directly from the abscess and mortality from a treatment complication. Continuous variables are expressed as mean standard deviation and are analysed using the Mann–Whitney test. Pearson’s w2 test or Fisher exact test (when expected frequencies were <5) were used to compare qualitative variables between both groups. The level of significance was established at 5% for all the calculations. R E SULT S General features There were 63 patients with PHA during the study period. Of these, 11 (17.5%) were correctly diagnosed in the ER (group A), and 52 (82.5%) were admitted without a specific diagnosis (group B). The mean age at admission was 59.8 16.5 years for the whole sample. In group A, the mean age was 49.3 8.8 years, and in group B it was 61.9 15.3 years (P ¼ 0.03). There were 26 patients older than 65 years. Of these, diagnosis was only suspected in two cases (7.7%). In the group of patients younger than 65 years (37 cases), PHA was suspected in nine patients (24.3%). The ratios of males to females were 1.2 : 1.0 in the group of patients with PHA diagnosed at ER (group A), and 1.7 : 1.0 in group B. The mean duration of symptoms before ER evaluation was 8.8 8.2 days versus 12.6 14.5 in groups A and B respectively.
Table 1 Main clinical manifestations and physical examination findings of the patients
Features
Group A n (%)
Group B n (%)
Fever Abdominal pain Chills Asthenia Anorexia Weight loss Ascites Jaundice Hepatomegaly
7 (63.3) 4 (36.4) 5 (45.5) 4 (36.4) 2 (18.2) 2 (18.2) ^ 5 (45.5) 2 (18.2)
41 (78.8) 24 (46.2) 17 (32.7) 14 (26.9) 12 (23.1) 11 (21.2) 2 (3.8) 11 (21.2) 11 (21.2)
In group B, hepatomegaly was detected more frequently than in group A (Table 1). No statistically significant difference was detected between the groups, although there was a trend towards a greater presence of jaundice at admission in group A patients (P ¼ 0.09). Predisposing conditions Table 2 shows the predisposing conditions found in both groups of patients. A past medical history of orthotopic liver transplantation (P ¼ 0.001) or biliary tract disease (P ¼ 0.05) favored a diagnosis of PHA in the ER. Globally, antecedent hepatobiliary disorders (including orthotopic liver transplantation), lead to a higher index of suspicion in the ER clinicians (P ¼ 0.004). Some form of immunosuppression was detected in five out of 11 patients in group A, and in seven out of 45 in group B (P ¼ 0.02). Other predisposing conditions found in our patients were as follows: alcoholism (two cases); recent (in the previous week) abdominal surgery (two patients); chronic brucellosis (one case); steroidal and immunosuppressive therapy (one patient with rheumatoid arthritis and one case of systemic vasculitis, respectively). Radiological findings A radiograph of the chest showed a greater number of patients with laminar atelectasis (P ¼ 0.09), and pleural effusion Table 2 Main predisposing conditions of patients with PHA
Presenting symptoms and physical examination The chief complaint in the ER was fever; seven cases (63.3%) in group A, and 41 (78.8%) in group B. Fever was noticed by 22 of 26 patients older than 65 years. Abdominal pain was reported more frequently by group B patients (24 cases versus four in group A). Chills were noticed by five patients (45.5%) in group A, and by 17 (32.7%) individuals in group B. During the physical examination, jaundice was noted in five patients of group A (45.5%), and only in 11 (21.2%) of group B.
Predisposing conditions
Group A n (%)
Group B n (%)
P value
HIV infection Liver transplant recipient Biliary tract disease Concomitant neoplasma Diabetes mellitus
^ 5 (45.5) 5 (45.5) ^ ^
5 (9.6) 2 (3.8) 9 (17.3) 5 (9.6) 9 (17.3)
NS 0.001 0.05 NS NS
a Cholangiocarcinoma (three cases), colorectal neoplasms (two patients). HIV, human immunodeficiency virus; NS, not significant.
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Concise Communications
Table 3 Chest X-ray findings in both groups of patients
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Table 4 Microbiological findings in the whole sample
Radiograph of the chest
Group A n (%)
Group B n (%)
Micro-organism group
n (%)
Atelectasis Pleural effusion Elevated right hemidiaphragm
3 (27.3) 6 (54.5) 1 (9.1)
4 (7.7) 15 (28.8) 5 (9.6)
Gram negative
22 (34.9)
Gram positive
11 (17.5)
Anaerobes
5 (7.9)
(P ¼ 0.1) in group A than in group B (see Table 3). Globally, radiological alterations (atelectasis, pleural effusion, or elevated right hemidiaphragm) on plain chest films were more frequent in the patients correctly diagnosed in the ER (P ¼ 0.05). Abdominal US was performed in all the cases diagnosed in the ER (Figure 1). PHA were multiple in five cases (45.5%) of group A (Figure 2), and in 25 (48.1%) of group B patients. In group A, there was one case (9.1%) of concomitant splenic
None
Most frequent species (n) Escherichia coli (8) Klebsiella pneumoniae (7) Enteroccoccus faecalis (4) Viridans streptococci (3) Prevotella spp. (2) Bacteroides fragilis (1)
25 (39.7)
abscesses, and six of these cases (11.5%) in group B. Ascites was demonstrated in two patients in each group (18.2% versus 3.8%, P < 0.001) using US, but it was clinically detected only in group B patients (both with a previous diagnosis of cholangiocarcinoma). Laboratory parameters No difference was found in the hematological values or in the liver function tests of both groups of patients. Only a trend towards a greater increase of the erythrocyte sedimentation rate was noted in the group A patients in comparison to group B (84 versus 60 mm/h; P ¼ 0.07). Microbiological data The causative micro-organisms did not differ between the groups; enteric Gram-negative bacilli being the most frequently isolated. Table 4 shows the main microbiological data of the whole sample.
Figure 1 Abdominal ultrasonography showing a large and heterogeneous hepatic collection.
Outcome The length of stay of group A patients was 45.0 50.4 days, and 34.3 22.1 days in the group B. There were two cases of recurrent PHA in the group of patients diagnosed in the ER, and seven in group B. Two out of 11 patients (18.2%) in group A, and seven out of 52 (13.5%) patients in group B, died. DI SC US S ION
Figure 2 Contrast enhanced CT-scan showing two multiloculated hepatic abscesses affecting both lobes.
Based upon the lack of specificity of clinical symptoms and signs, as well as laboratory parameters, diagnosing PHA remains a difficult task for the clinician. This is particularly important in the ER, since the time for a patient’s evaluation is often limited. A diagnosis of suspicion of PHA was made in the ER in nearly one-sixth of our patients. The patients correctly diagnosed at admission were younger than the patients undiagnosed. Thus, in this study, age was an important clue when deciding to request an US examination in patients suspected of having a PHA. PHA was traditionally considered as a subacute entity, with a median of symptom duration before admission of over 2 weeks
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[8]. However, in our series the median duration of symptoms prior to ER evaluation was 9 days in the group A patients. It has been suggested that the underlying condition may influence the presentation in an individual patient [9]. In our study this may be explained, at least in part, by the greater presence of liver transplantation recipients in group A. The presence of fever or abdominal pain in these patients, probably leads to a prompt medical consultation. A past medical history of orthotopic liver transplantation or biliary tract disorders, also led to a higher index of suspicion by the ER clinicians. In fact, 10 out of 11 patients correctly diagnosed had one of these conditions. The combination of fever and right upper quadrant pain, classically associated with PHA, was only found in 19 (30.1%) patients in our series, reflecting the non-specific nature of clinical presentation in many cases, and the difficulty of an early diagnosis [10]. Physical examination data were not helpful for the physicians in the ER in most of the cases. In this regard, a classical sign such as jaundice was present in only one-quarter of our cases. However, it was the only feature that led to a more accurate diagnosis (45.5% of group A vesrus 21.2% of group B), although its importance did not reach statistical significance in our study, probably due to the size of the sample. Chest radiographs showed laminar atelectasis in nearly onethird of the group A patients, associated with right pleural effusion in half of them. These findings are consistent with those previously published in the literature [10]. In the setting of a patient with a clinical suspicion of PHA, these chest X-ray abnormalities probably reinforced the diagnosis, as our study suggest. At admission, the presence of multiple abscesses in the US study did not correlate with a more accurate diagnosis, although they were more frequently detected in immunosuppressed patients, as the literature states [8,10]. According to the chest X-ray findings, there were no differences in the accuracy of the diagnosis of suspicion between the groups, although radiographic abnormalities were more frequent in the group with multiple PHA, particularly laminar atelectasis and pleural effusion. The higher rate of immunosuppression added to the fact that hematogenous spread was predominant in this group, may explain the remarkable incidence of splenic abscesses in these patients. Laboratory parameters were not helpful to the ER clinicians to increase their index of suspicion for PHA. Retrospectively, causative micro-organisms were not different between both groups, and no severity patterns could be related to the etiological agent at admission. There was no association between a correct diagnosis in the ER and the length of stay, nor with the rates of recurrence or mortality. The most important determinant of mortality in our patients, appeared to be the presence of severe underlying diseases, as Seeto and Rockey have already pointed out [5].
In this regard, we found a higher rate of immunosuppressed patients in group A, which could certainly affect the length of stay and the prognosis in our series. The two main limitations of our study are the size of the sample and its retrospective nature. However, in the case of PHA, large and prospective studies are lacking and, to our knowledge, none of them are focused on the accuracy of diagnosis in the ER. In summary, diagnosing PHA in the ER remains a challenging problem for the clinician owing to the paucity of the symptoms and signs. In this study, we have found a subgroup of patients with a high index of suspicion for PHA at admission; younger, immunosuppressed, and with a past medical history of biliary tree disorders. Conversely, an early diagnosis was a difficult task in elderly patients. Therefore, the first evaluation of an occult liver abscess may be improved by a history directed to identification predisposing conditions, mainly immunosuppression and hepatobiliary disorders. The presence of right atelectasis or pleural effusion in the chest radiograph could reinforce this suspicion in most of the patients, even in the absence of the classical clinical features. In these cases, an abdominal US or CT study would be strongly advised. ACK NOW L EDGME N T S Part of this work was present at the XXV World Congress of Internal Medicine in Cancun, Mexico, June 2000. R EFER E NCE S 1. Hansen PS, Schonheyder HC. Pyogenic hepatic abscess. A 10-year population-based retrospective study. APMIS 1998; 106: 396–402. 2. Jimenez E, Tiberio G, Sanchez J, Jimenez FJ, Jimenez G. Pyogenic hepatic abscesses: 16 years experience in its diagnosis and treatment. Enferm Infecc Microbiol Clin 1998; 16: 307–11. 3. Koneru S, Peskin GW, Sreenivas V. Pyogenic hepatic abscess in a community hospital. Am Surg 1994; 60: 278–81. 4. Hashimoto L, Hermann R, Grundfest-Broniatowski S. Pyogenic hepatic abscess: results of current management. Am Surg 1995; 61: 407–11. 5. Seeto RK, Rockey DC. Pyogenic liver abscess. Changes in etiology, management and outcome. Medicine (Baltimore) 1996; 75: 99–113. 6. Huang CJ, Pitt HA, Lipsett PA et al. Pyogenic hepatic abscess. Changing trends over 42 years. Ann Surg 1996; 223: 600–7. 7. Chou F, Sheen-Chen S, Chen Y, Chen M. Single and multiple pyogenic liver abscesses: clinical course, etiology, and results of treatment. World J Surg 1997; 21: 384–9. 8. Bamberger DM. Outcome of medical treatment of bacterial abscesses without therapeutic drainage. Review of cases reported in the literature. Clin Infect Dis 1996; 23: 592–603. 9. Smoger SH, Mitchell CK, McClave SA. Pyogenic liver abscesses: a comparison of older and younger patients. Age Ageing 1998; 27: 443–8. 10. Johannsen EC, Sifri CD, Madoff LC. Pyogenic liver abscesses. Infect Dis Clin North Am 2000; 14: 547–63.
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 7, 565–570
Confirmation of meningococcal disease by urinary antigen testing S. C. Clarke, J. Reid, L. Thom and G. F. S. Edwards Scottish Meningococcus and Pneumococcus Reference Laboratory, House on the Hill, Stobhill Hospital, Glasgow G21 3UW, UK
Tel/Fax: þ44 141201 3836
E-mail: [email protected]
The meningococcus is an important cause of morbidity and mortality and a rapid laboratory diagnosis is required through accurate, non-culture-based methods. Body fluids that are easily obtainable are preferred for this route of diagnosis and urine is the specimen of choice as it can be obtained non-invasively. Urine samples were tested from patients with suspected meningococcal disease and tested by latex agglutination and PCR. It was shown that urinary PCR is not useful for the laboratory confirmation of MD but latex agglutination testing may be useful in certain settings prior to confirmatory testing by a reference laboratory. Keywords Urine, meningococci, antigen, polymerase chain reaction Accepted 3 July 2001
The meningococcus is one of the main causes of meningitis, particularly in countries where conjugate vaccines against Haemophilus influenzae type b disease have been introduced, and is an important cause of morbidity and mortality [1,2]. The search for new therapeutic and diagnostic methods therefore continues, with the aims of reducing the morbidity and mortality associated with meningococcal disease (MD), and performing effective surveillance of the disease. Although polysaccharide vaccines have been available for the prevention of a number of serogroups of MD, these vaccines have generally had a short duration of protection and could not be used in young children. New conjugate vaccines are now available for the prevention of serogroup C MD [3,4], but there are no conjugate vaccines yet available for the prevention of other invasive meningococcal serogroups. As technology improves, new methods are becoming available for the laboratory confirmation of MD. These include PCR and DNA sequencing methods [5,6]. Automation is also becoming increasingly used as it becomes affordable [7]. However, most of these methods are limited to specialised laboratories and therefore result in reporting delays. To enable a rapid diagnosis of MD to be made local diagnostic microbiology laboratories require access to quick but accurate methods [8]. Owing to the common use of antibiotics prior to hospital admission [9], non-culture confirmation of disease is important, although every effort should be made to gain a culture confirmation. Methods are therefore required that can provide a rapid, accurate and non-culture diagnostic route to confirm a clinical suspicion of MD. Body fluids that are easily obtainable are preferred for this route of diagnosis, and urine is the specimen of choice, because it can usually be obtained non-invasively. As all PCR requests for the laboratory confirmation of MD in Scotland are forwarded to the Scottish Meningococcus and Pneumococcus Reference Laboratory (SMPRL), and there is a delay
due to postal and testing time, testing for urinary antigen would be a rapid and cost-effective screening method for MD in a local diagnostic laboratory. Urines that are positive by latex agglutination could then be forwarded to the reference laboratory for further testing. Two preliminary studies have been performed for the rapid detection of meningococcal antigen in urine [10,11], but the number of samples used was small. Here we describe the usefulness of latex agglutination and PCR testing on unconcentrated and concentrated urine for the laboratory confirmation of MD. A request was made to all diagnostic microbiology laboratories throughout Scotland to send urine samples from patients suspected of having MD. Urines were taken at the onset of illness and sent to the SMPRL for testing. All testing was performed on unconcentrated and concentrated urine. Unconcentrated urine was boiled for 5 min Concentration of urine was initially performed with 5 mL, using the commercially available Millipore Minicon B15 concentration system (Amicon, Millipore, Watford, UK), according to the manufacturer’s instructions. However, this was found to result in inhibition of the PCR reaction, and was therefore replaced with the Vivapore 5 (Sartorius, Epsom, Surrey, UK), a similar method that could be used for comparison. After concentration, the urine was again boiled for 5 min Unconcentrated and concentrated urines were tested for the presence of meningococcal antigen using the Wellcogen latex agglutination test (Abbot Diagnostics, Maidenhead, UK). Urines that were positive for serogroups A, C, Yand W135 by latex agglutination were tested further by coagglutination to determine the individual serogroup [12]. Unconcentrated and concentrated urines were also tested for the presence of meningococcal antigen, using PCR to detect the insertion element IS1106, as previously described [13,14]. Between August 1999 and July 2000, a total of 133 urines were received from 128 patients and tested for the presence of
ß 2001 Copyright by the European Society of Clinical Microbiology and Infectious Diseases
566 Clinical Microbiology and Infection, Volume 7 Number 10, October 2001
Table 1 Positive results from antigen testing of unconcentrated and concentrated urine by latex agglutination and PCR
Urine
Latex serogroup
Unconcentrated PCR
Concentrated PCR
1 2 3 4 5 6 7 8 9
B B B B C C B C Negative
Negative Negative Negative Negative Negative Negative Negative Negative Negative
Negative Negative Inhibitor present Negative Inhibitor present Negative Negative Negative Positive
meningococcal antigen as described. The first 59 urines were tested by the Millipore Minicon B15 method, and eight urines were positive for meningococcal antigen by latex agglutination, as previously reported [11]. Five of these were serogroup B, and three were serogroup C. The remaining 51 urines were negative by latex agglutination. Only one urine of these 51 was positive by PCR after concentration (urine 9, Table 1), and it had been negative by latex agglutination. Further testing on this patient by a meningococcal outer membrane protein (OMP) serum antibody ELISA method suggested that the patient did not have MD. PCR inhibition factors were present in eight (14%) unconcentrated urines and 19 (32%) concentrated urines. Owing to the high number of urines possessing these inhibition factors after concentration using the Millipore system, the concentration technique was replaced with the Vivapore 5 system. A further 74 urines were tested by latex agglutination and PCR. No urines were positive by either latex agglutination or PCR when unconcentrated or concentrated samples were used. Inhibition factors were again common, being found in 37 (50%) of samples. Summarised results are shown in Table 2. Antigen detection tests are routinely used by the SMPRL and can provide sensitive and specific methods for the confirmation of MD [6]. Blood or cerebrospinal fluid are the samples routinely used for antigen detection, because urine has never been evaluated for its usefulness. However, it is well known that latex agglutination tests, although highly sensitive, often produce false positives, particularly in the presence of proteins normally found in urine [15]. Latex agglutination could be used as a screening assay, followed by the PCR test as a more sensitive and specific assay, with the possibility of confirming the Table 2 PCR inhibition information using two commercially available concentration systems Commercial system
Unconcentrated
Concentrated
Minicon B15 Vivapore 15
8 (16%) 15 (20%)
19 (37%) 37 (50%)
serogroup of infection using the siaD PCR method [16]. In this study, 133 urine samples from 128 patients with suspected MD were analyzed. Concentration of the urine did not affect the latex agglutination result. Three of the latex agglutinationpositive urines were confirmed by other methods, while the other five were not confirmed, either because other tests were negative or because no other samples were received. Latex agglutination of urine for the confirmation of MD may therefore be useful as an urgent measure for confirming and obtaining the serogroup of the infecting meningococcus in local diagnostic laboratories where PCR testing is not available. Further testing and confirmation may then be achieved at a reference laboratory, where other tests using samples other than urine, such as whole blood or cerebrospinal fluid, may be used. The urinary PCR test was not useful for the laboratory confirmation of MD. All but one of the urines tested were negative for the insertion element IS1106, using both unconcentrated and concentrated urine. The concentrated urine that was positive by PCR was not confirmed by other methods and may have been a false-positive result. The concentration of urine using either commercial system increased the number of urines that exhibited factors resulting in inhibition of the PCR reaction. These factors may cause such inhibition by reducing the amount of available magnesium ions in the PCR reaction mix [17]. Although this can be counteracted by increasing the magnesium ion concentration, the variability in the amount of inhibitor may result in a less rigid PCR assay for clinical diagnostic use. Normally, the IS1106 PCR assay is very useful for the laboratory confirmation of MD using other body fluids, such as whole blood or cerebrospinal fluid [6]. Although falsepositive results using this gene target have been reported [18], this was generally not a problem in this study. True positives can often be confirmed by other slightly less sensitive PCR assays that detect the ctrA and siaD genes, respectively [5,16], although this was not the case for this positive.
R EFER E NCE S 1. Achtman M. Global epidemiology of meningococcal disease. Meningococcal Dis 1995; 7: 159–75. 2. Noah N, Henderson B. Surveillance of bacterial meningitis in Europe 1997/98. London: Public Health Laboratory Service, 1998. 3. Chief Medical Officer. Introduction of immunisation against group C meningococcal infection. PAL51979. Health Department, Scotland, 1999. 4. Chief Medical Officer. Start of the New Meningococcal C Conjugate Vaccine Immunisation Programme. PL/CMO/99/4. London: Department of Health, England and Wales, 1999. 5. Guiver M, Borrow R, Marsh J et al. Evaluation of the Applied Biosystems automated Taqman polymerase chain reaction system for the detection of meningococcal DNA. FEMS Immunol Med Microbiol 2000; 28: 173–9. 6. Clarke SC, Edwards GFS. Guidance for requests and interpretation of services provided by the Scottish Meningococcus and
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Concise Communications
7.
8.
9. 10.
11. 12.
Pneumococcus Reference Laboratory. SCIEH Weekly Rep 2000; 34: 228–32. Clarke SC, Diggle MA, Reid JA, Thom L, Edwards GFS. Introduction of an automated service for the laboratory confirmation of meningococcal disease in Scotland. J Clin Pathol 2001; 54: 556–7. Gray SJ, Sobanski MA, Kaczmarksi EB et al. Ultrasound-enhanced latex immunoagglutination and PCR as complementary methods for non-culture-based confirmation of meningococcal disease. J Clin Microbiol 1999; 37: 1797–801. Cartwright K, Reilly S, White D, Stuart J. Early treatment with parenteral penicillin in meningococcal disease. Br Med J 1992; 305: 484. al-Wali W, Hughes C. Urine antigen detection can be quicker than PCR in the diagnosis of meningococcal disease. J Hosp Infect 1998; 40: 326–8. Clarke SC. Urinary antigen diagnosis of meningococcal disease. Br J Biomed Sci 2000; 57: 153–5. Eldridge J, Sutcliffe EM, Abbott JD, Jones DM. Serological grouping of meningococci and detection of antigen in cerebrospinal fluid by coagglutination. Med Lab Sci 1978; 35: 63–6.
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13. Ni H, Knight AI, Cartwright K, Palmer WH, McFadden J. Polymerase chain reaction for diagnosis of meningococcal meningitis. Lancet 1992; 340: 1432–4. 14. Newcombe J, Cartwright K, Palmer WH, McFadden J. PCR of peripheral blood for diagnosis of meningococcal disease. J Clin Microbiol 1996; 34(7): 1637–40. 15. Weinberg GA, Storch GA. Preparation of urine samples for use in commercial latex agglutination tests for bacterial antigens. J Clin Microbiol 1985; 21: 899–901. 16. Borrow R, Claus H, Guiver M et al. Non-culture diagnosis and serogroup determination of meningococcal B and C infection by a sialyltransferase (SiaD) PCR ELISA. Epidemiol Infect 1997; 118: 111–17. 17. Abu Al-Soud W, Ra˚dstro¨ m P. Purification and characterization of PCR-inhibitory components in blood cells. J Clin Microbiol 2001; 39: 485–93. 18. Borrow R, Guiver M, Sadler F et al. False positive diagnosis of meningococcal infection by the IS1106 PCR ELISA. FEMS Microbiol Lett 1998; 162: 215–18.
Pyogenic hepatic abscess: clues for diagnosis in the emergency room J. L. Herna´ndez and C. Ramos Department of Internal Medicine, Hospital Marque´ s de Valdecilla, Santander, Spain E-mail: [email protected] The objective of this paper is to describe the clinical and diagnostic characteristics of patients with pyogenic hepatic abscesses evaluated in the emergency room, and to know whether it is feasible to make an early diagnosis based on any of these characteristics. The setting was an urban, tertiary-care teaching hospital. This was a retrospective study of 63 adult patients admitted to our institution because of pyogenic liver abscesses from January 1991 to December 1998. Keywords Liver abscess, emergency care, diagnosis Accepted 8 June 2001
Clin Microbiol Infect 2001: 7: 567–570 IN T R ODUC T ION Pyogenic hepatic abscess (PHA) represents an infrequent and sometimes life-threatening entity [1]. Its recognition has clearly improved in the last decade through the development of more sensitive and specific imaging techniques, such as ultrasonography (US) and computed tomography (CT), with their relevant therapeutic implications [2,3]. Standard treatment protocols usually recommend a combination of drainage and antimicrobial therapy, although no specific antibiotic schemes have been defined due to the lack of large, prospective studies [4]. Diagnosing PHA in an initial stage remains a difficult task today, frequently due to the paucity of the presenting symptoms Corresponding author and reprint requests: Jose´ Luis Herna´ ndez, Department of Internal Medicine, Hospital Marque´ s de Valdecilla, University of Cantabria, 39008 Santander, Spain E-mail: [email protected]
or the radiological features. However, several studies have confirmed that an early diagnosis is associated with improved survival [5–7]. This study will describe the clinical and diagnostic characteristics of patients with PHA evaluated at a first-step hospital level, the emergency room (ER). PAT IE N T S AND ME T HOD S The medical records of all adult patients admitted between January 1991 and December 1998 at the Marque´ s de Valdecilla University Hospital, and discharged with a diagnosis of PHA, were reviewed. This is an 1100-bed tertiary-care center that serves as the reference hospital for a population of 500 000, and as the first-level hospital for an area including about 350 000 inhabitants in Northern Spain. Therefore, this population can be regarded as an unselected sample of this entity in our area.
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568 Clinical Microbiology and Infection, Volume 7 Number 10, October 2001
Data were obtained by a retrospective review of clinical charts of patients with PHA, selected through the computerised database of the Admissions and Clinical Documentation Department. PHA was defined on the evidence of one or more liver collections without radiological characteristics of malignancy, in US or CT studies, along with the identification of pus or bacteria, either microscopically or by culture [5]. For the purposes of the study, patients were divided into two different groups. Those patients in whom a diagnosis of PHA was reached in the ER, constituted group A. Group B contained those patients in whom PHA was not detected in the ER evaluation. The median follow-up of patients was 12 months. Data on recurrence and mortality were also collected. PHA-related mortality included both mortality resulting directly from the abscess and mortality from a treatment complication. Continuous variables are expressed as mean standard deviation and are analysed using the Mann–Whitney test. Pearson’s w2 test or Fisher exact test (when expected frequencies were <5) were used to compare qualitative variables between both groups. The level of significance was established at 5% for all the calculations. R E SULT S General features There were 63 patients with PHA during the study period. Of these, 11 (17.5%) were correctly diagnosed in the ER (group A), and 52 (82.5%) were admitted without a specific diagnosis (group B). The mean age at admission was 59.8 16.5 years for the whole sample. In group A, the mean age was 49.3 8.8 years, and in group B it was 61.9 15.3 years (P ¼ 0.03). There were 26 patients older than 65 years. Of these, diagnosis was only suspected in two cases (7.7%). In the group of patients younger than 65 years (37 cases), PHA was suspected in nine patients (24.3%). The ratios of males to females were 1.2 : 1.0 in the group of patients with PHA diagnosed at ER (group A), and 1.7 : 1.0 in group B. The mean duration of symptoms before ER evaluation was 8.8 8.2 days versus 12.6 14.5 in groups A and B respectively.
Table 1 Main clinical manifestations and physical examination findings of the patients
Features
Group A n (%)
Group B n (%)
Fever Abdominal pain Chills Asthenia Anorexia Weight loss Ascites Jaundice Hepatomegaly
7 (63.3) 4 (36.4) 5 (45.5) 4 (36.4) 2 (18.2) 2 (18.2) ^ 5 (45.5) 2 (18.2)
41 (78.8) 24 (46.2) 17 (32.7) 14 (26.9) 12 (23.1) 11 (21.2) 2 (3.8) 11 (21.2) 11 (21.2)
In group B, hepatomegaly was detected more frequently than in group A (Table 1). No statistically significant difference was detected between the groups, although there was a trend towards a greater presence of jaundice at admission in group A patients (P ¼ 0.09). Predisposing conditions Table 2 shows the predisposing conditions found in both groups of patients. A past medical history of orthotopic liver transplantation (P ¼ 0.001) or biliary tract disease (P ¼ 0.05) favored a diagnosis of PHA in the ER. Globally, antecedent hepatobiliary disorders (including orthotopic liver transplantation), lead to a higher index of suspicion in the ER clinicians (P ¼ 0.004). Some form of immunosuppression was detected in five out of 11 patients in group A, and in seven out of 45 in group B (P ¼ 0.02). Other predisposing conditions found in our patients were as follows: alcoholism (two cases); recent (in the previous week) abdominal surgery (two patients); chronic brucellosis (one case); steroidal and immunosuppressive therapy (one patient with rheumatoid arthritis and one case of systemic vasculitis, respectively). Radiological findings A radiograph of the chest showed a greater number of patients with laminar atelectasis (P ¼ 0.09), and pleural effusion Table 2 Main predisposing conditions of patients with PHA
Presenting symptoms and physical examination The chief complaint in the ER was fever; seven cases (63.3%) in group A, and 41 (78.8%) in group B. Fever was noticed by 22 of 26 patients older than 65 years. Abdominal pain was reported more frequently by group B patients (24 cases versus four in group A). Chills were noticed by five patients (45.5%) in group A, and by 17 (32.7%) individuals in group B. During the physical examination, jaundice was noted in five patients of group A (45.5%), and only in 11 (21.2%) of group B.
Predisposing conditions
Group A n (%)
Group B n (%)
P value
HIV infection Liver transplant recipient Biliary tract disease Concomitant neoplasma Diabetes mellitus
^ 5 (45.5) 5 (45.5) ^ ^
5 (9.6) 2 (3.8) 9 (17.3) 5 (9.6) 9 (17.3)
NS 0.001 0.05 NS NS
a Cholangiocarcinoma (three cases), colorectal neoplasms (two patients). HIV, human immunodeficiency virus; NS, not significant.
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Table 3 Chest X-ray findings in both groups of patients
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Table 4 Microbiological findings in the whole sample
Radiograph of the chest
Group A n (%)
Group B n (%)
Micro-organism group
n (%)
Atelectasis Pleural effusion Elevated right hemidiaphragm
3 (27.3) 6 (54.5) 1 (9.1)
4 (7.7) 15 (28.8) 5 (9.6)
Gram negative
22 (34.9)
Gram positive
11 (17.5)
Anaerobes
5 (7.9)
(P ¼ 0.1) in group A than in group B (see Table 3). Globally, radiological alterations (atelectasis, pleural effusion, or elevated right hemidiaphragm) on plain chest films were more frequent in the patients correctly diagnosed in the ER (P ¼ 0.05). Abdominal US was performed in all the cases diagnosed in the ER (Figure 1). PHA were multiple in five cases (45.5%) of group A (Figure 2), and in 25 (48.1%) of group B patients. In group A, there was one case (9.1%) of concomitant splenic
None
Most frequent species (n) Escherichia coli (8) Klebsiella pneumoniae (7) Enteroccoccus faecalis (4) Viridans streptococci (3) Prevotella spp. (2) Bacteroides fragilis (1)
25 (39.7)
abscesses, and six of these cases (11.5%) in group B. Ascites was demonstrated in two patients in each group (18.2% versus 3.8%, P < 0.001) using US, but it was clinically detected only in group B patients (both with a previous diagnosis of cholangiocarcinoma). Laboratory parameters No difference was found in the hematological values or in the liver function tests of both groups of patients. Only a trend towards a greater increase of the erythrocyte sedimentation rate was noted in the group A patients in comparison to group B (84 versus 60 mm/h; P ¼ 0.07). Microbiological data The causative micro-organisms did not differ between the groups; enteric Gram-negative bacilli being the most frequently isolated. Table 4 shows the main microbiological data of the whole sample.
Figure 1 Abdominal ultrasonography showing a large and heterogeneous hepatic collection.
Outcome The length of stay of group A patients was 45.0 50.4 days, and 34.3 22.1 days in the group B. There were two cases of recurrent PHA in the group of patients diagnosed in the ER, and seven in group B. Two out of 11 patients (18.2%) in group A, and seven out of 52 (13.5%) patients in group B, died. DI SC US S ION
Figure 2 Contrast enhanced CT-scan showing two multiloculated hepatic abscesses affecting both lobes.
Based upon the lack of specificity of clinical symptoms and signs, as well as laboratory parameters, diagnosing PHA remains a difficult task for the clinician. This is particularly important in the ER, since the time for a patient’s evaluation is often limited. A diagnosis of suspicion of PHA was made in the ER in nearly one-sixth of our patients. The patients correctly diagnosed at admission were younger than the patients undiagnosed. Thus, in this study, age was an important clue when deciding to request an US examination in patients suspected of having a PHA. PHA was traditionally considered as a subacute entity, with a median of symptom duration before admission of over 2 weeks
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[8]. However, in our series the median duration of symptoms prior to ER evaluation was 9 days in the group A patients. It has been suggested that the underlying condition may influence the presentation in an individual patient [9]. In our study this may be explained, at least in part, by the greater presence of liver transplantation recipients in group A. The presence of fever or abdominal pain in these patients, probably leads to a prompt medical consultation. A past medical history of orthotopic liver transplantation or biliary tract disorders, also led to a higher index of suspicion by the ER clinicians. In fact, 10 out of 11 patients correctly diagnosed had one of these conditions. The combination of fever and right upper quadrant pain, classically associated with PHA, was only found in 19 (30.1%) patients in our series, reflecting the non-specific nature of clinical presentation in many cases, and the difficulty of an early diagnosis [10]. Physical examination data were not helpful for the physicians in the ER in most of the cases. In this regard, a classical sign such as jaundice was present in only one-quarter of our cases. However, it was the only feature that led to a more accurate diagnosis (45.5% of group A vesrus 21.2% of group B), although its importance did not reach statistical significance in our study, probably due to the size of the sample. Chest radiographs showed laminar atelectasis in nearly onethird of the group A patients, associated with right pleural effusion in half of them. These findings are consistent with those previously published in the literature [10]. In the setting of a patient with a clinical suspicion of PHA, these chest X-ray abnormalities probably reinforced the diagnosis, as our study suggest. At admission, the presence of multiple abscesses in the US study did not correlate with a more accurate diagnosis, although they were more frequently detected in immunosuppressed patients, as the literature states [8,10]. According to the chest X-ray findings, there were no differences in the accuracy of the diagnosis of suspicion between the groups, although radiographic abnormalities were more frequent in the group with multiple PHA, particularly laminar atelectasis and pleural effusion. The higher rate of immunosuppression added to the fact that hematogenous spread was predominant in this group, may explain the remarkable incidence of splenic abscesses in these patients. Laboratory parameters were not helpful to the ER clinicians to increase their index of suspicion for PHA. Retrospectively, causative micro-organisms were not different between both groups, and no severity patterns could be related to the etiological agent at admission. There was no association between a correct diagnosis in the ER and the length of stay, nor with the rates of recurrence or mortality. The most important determinant of mortality in our patients, appeared to be the presence of severe underlying diseases, as Seeto and Rockey have already pointed out [5].
In this regard, we found a higher rate of immunosuppressed patients in group A, which could certainly affect the length of stay and the prognosis in our series. The two main limitations of our study are the size of the sample and its retrospective nature. However, in the case of PHA, large and prospective studies are lacking and, to our knowledge, none of them are focused on the accuracy of diagnosis in the ER. In summary, diagnosing PHA in the ER remains a challenging problem for the clinician owing to the paucity of the symptoms and signs. In this study, we have found a subgroup of patients with a high index of suspicion for PHA at admission; younger, immunosuppressed, and with a past medical history of biliary tree disorders. Conversely, an early diagnosis was a difficult task in elderly patients. Therefore, the first evaluation of an occult liver abscess may be improved by a history directed to identification predisposing conditions, mainly immunosuppression and hepatobiliary disorders. The presence of right atelectasis or pleural effusion in the chest radiograph could reinforce this suspicion in most of the patients, even in the absence of the classical clinical features. In these cases, an abdominal US or CT study would be strongly advised. ACK NOW L EDGME N T S Part of this work was present at the XXV World Congress of Internal Medicine in Cancun, Mexico, June 2000. R EFER E NCE S 1. Hansen PS, Schonheyder HC. Pyogenic hepatic abscess. A 10-year population-based retrospective study. APMIS 1998; 106: 396–402. 2. Jimenez E, Tiberio G, Sanchez J, Jimenez FJ, Jimenez G. Pyogenic hepatic abscesses: 16 years experience in its diagnosis and treatment. Enferm Infecc Microbiol Clin 1998; 16: 307–11. 3. Koneru S, Peskin GW, Sreenivas V. Pyogenic hepatic abscess in a community hospital. Am Surg 1994; 60: 278–81. 4. Hashimoto L, Hermann R, Grundfest-Broniatowski S. Pyogenic hepatic abscess: results of current management. Am Surg 1995; 61: 407–11. 5. Seeto RK, Rockey DC. Pyogenic liver abscess. Changes in etiology, management and outcome. Medicine (Baltimore) 1996; 75: 99–113. 6. Huang CJ, Pitt HA, Lipsett PA et al. Pyogenic hepatic abscess. Changing trends over 42 years. Ann Surg 1996; 223: 600–7. 7. Chou F, Sheen-Chen S, Chen Y, Chen M. Single and multiple pyogenic liver abscesses: clinical course, etiology, and results of treatment. World J Surg 1997; 21: 384–9. 8. Bamberger DM. Outcome of medical treatment of bacterial abscesses without therapeutic drainage. Review of cases reported in the literature. Clin Infect Dis 1996; 23: 592–603. 9. Smoger SH, Mitchell CK, McClave SA. Pyogenic liver abscesses: a comparison of older and younger patients. Age Ageing 1998; 27: 443–8. 10. Johannsen EC, Sifri CD, Madoff LC. Pyogenic liver abscesses. Infect Dis Clin North Am 2000; 14: 547–63.
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