Radiologic tests for infectious disease diagnosis

Clinical Microbiology Newsletter I

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Vol. 16, No. 1

Jammry 1, 1994

Radiologic Tests for Infectious Disease Diagnosis Giles W. Boland, M.D. Department of Radiology Massachusetts General Hospital Harvard Medical School Boston, MA 02114

Advances in the microbiologic investigation and diagnosis of infectious disease have been paralleled in the last two decades by the rapid development of new radiologic techniques. These newer imaging modalities have significantly improved the sensitivity in the detection of the source and type of infection in sepsis patients. Imaging tests frequently provide the fh-st objective evidence that infection is present. Radiologic tests, therefore, play a key role in the diagnosis and follow-up of many infectious disease processes. Despite the dependence of clinicians on radiologic tests for the diagnosis of infectious disease, there are no truly specificimaging techniques for infections. All tests available to the radiologist either detect the presence of inflammation or detect macroscopic evidence of disease. Although this may suggest infection, other specific disease processes may have similar appearances. It is therefore essential that any abnormality detected by a radiologic test be correlated with the clinical f'mdings and results from other investigations. A further caveat to the use of imaging techniques is the trend toward the use of more expensive technology when basic radiologictestsmay suffice. A computed tomographic (CT) scan of the chest may identify precise pncumonic infiltration in the lung, but a chest x ray will provide similar informaC M N E E J 16(I)14,1994

tion at minimal cost and inconvenience to the patient. In addition, an understanding of the radiation doses involved in some of the newer technologies should lead to caution on behalf of the referring physician. For instance, the radiation dose received during a chest CT is over 1130times that of a chest x ray (1). Therefore, the newer technologies should be applied with caution and in cases where they are likely to provide significant additional information that may alter the management of the patient. Each available imaging test has inherent limitations in its clinical applicability. Imaging methods such as plain film radiography, contrast studies, CT, ultrasound, and magnetic resonance imaging (MRI) can generally detect only macroscopic anatomical changes. Radionuclide tests, in contrast, detect inflammation even if it is not associated with structural change. This article will discuss the radiologic tests available and their applications for investigating infection in specific organs. Radiologic Techniques For infections occurring outside the brain, the initial radiologic test when indicated isthe plain radiograph. Although it can provide accurate information about the type and site of infection in areas such as the chest, in other organs it is relatively insensitive--large structural or destructive changes need to have occurred before an abnormality is detected. It can, however, act as a baseline measure in the follow-up of diagnosed disease. The use of contrast agents can enhance detection and localElsevier

ization of infection and further define its extent. These include barium studies of the abdomen, which provide nonspecific evidence of infection ~ the small or large intestine; injection of water-soluble contrast agents into abscess cavities; and intravenous and intraarterial injection of contrast agents that can provide evidence of infection in areas such as the kidney or brain. Computed tomography has transformed the detection and management of infectious disease processes. It can provide precise cross-sectional information about the extent and site of infection and is the modality of choice for abscess detection with a sensitivity greater than 95% (2). It also provides anatomic information for planning aspiration or drainage (either radiologic or surgical) of abscess formation in any organ including the brain. The administra-

In This Issue

Radioiogic Tests for Infectious D sease V i a g u i s

...............

t

H o w newer imaging methods such as

computed tomographic ecan, ultrasound, magnetic resonance imaging, and radionuclide tests can enhance the diagnosis o f infection

Bacteremia Caused by TsukamureUa Species . . . . . . . . . . . .

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tion of intravenous contrast media may increase the sensitivity for the detection of areas of inflammation by identifying either a marked vascular component or an increase in capillary permeability into surrounding areas of inflammation. Ultrasound allows rapid noninvasive evaluation of the patient and it is most useful in abdominal imaging, particularly for suspected abscess collections. However, the sound beam is attenuated by overlying air in lung and bowel and by bony structures and is therefore limited for investigations within lung parenchyma and the brain and for deep inWaabdominal collections. Magnetic resonance imaging (MRI) is the newest and most expensive radiologic test available and is most useful for detection of abnormalities in the brain or musculoskeletal system. In other areas its use is limited by motion artifact from the lung, great vessels, and bowel. Compared with other imaging modalities, it provides superior definition of the extent of edema associated with infection. The administration of intravenous contrast media can be useful in a similar fashion to contrast-enhanced CT scans. Scintigraphic imaging of infection rests on identification of inflammation and cannot differentiate between infectious and noninfectious inflammatory disease. However, radiouuclide studies are generally more sensitive than other imaging modalities at detecting infection because they depend on white cell migration or changes in blood flow or permeability to show inflammation. The distribution of radioisotope paralIris the acute inflammatory response associated with infection and tends to he greater in acute sites of inflammation than in areas of chrouic inflammation. This high sensitivity is the chief strength of nuclear imaging. It is particularly helpful in the detection of infection in a patient with a fever of

unknown origin because it then directs attention to that region. To arrive at a meaningful clinical diagnosis, the site of the inflammation must then be correlated with an anatomic structure that may require additional imaging modalities such as CT or MRI. Radioisotopes available include 67Gallium, which after injection binds to circulating proteins (3) and is rapidly localized in areas of inflammation through increased capillary permeability. Leukocytes can be labeled with radioisotopes, and if there is marked white cell migration into a region of infection, radiolabeled white cells will provide a pictorial representation of the inflammatory response. White cells axe usually labeled with indium- 111 although 99mTechnetium-HMPAO-labeled white cells have recently been investigated but the ultimate role of this method is still uncertain. Finally, radionuclide-laheled antibodies to bacteria have been investigated. Only indium-111-labeled IgG has proved useful and further studies are awaited. Radiologic Imaging of Infections in Specific Organs The Brain There have been extensive recent reports as to the radiologic manifestations of HIV in the brain. In HIV encephalitis, CT and MR scans may be normal or show atrophy or white matter lesions. White matter lesions are hypodense on CT or hyperintense on T2-weighted MR images reflecting edematous changes. Normal MR scans are much more common in neurologically intact patients than in those with neurologic symptoms (87% versus 54%) (4). Symptomatic patients had more white matter lesions involving a larger area of the brain and involving infratentorial portions of the brain (4). Early recognition by MRI of HIV encephalitis is, however, diffieult at present and it is generally accepted

that radiologic findings lag behind clinical fmdings. Radioiogic findings that suggest demyelination are thought to be the result of a secondary inflammatory reaction to the basic pathological process of microglial nodule formation. The CT evaluation of HIV encephalitis is less sensitive than MRI, but AIDS patients show significantly enlarged ventricles and a trend toward sulcal enlargement compared with healthy control patients (5). In HIV-positive patients who do not have AIDS, focal lesions are found only in patients with focal neurologic signs or symptoms. Nonfocal clinical findings are associated with either a normal CT scan, hydrocephalus, or atrophy (6). MRI is generally considered the best imaging method for examining AIDS patients with possible intracranial disease. A recent study has shown that MRI was 44% more sensitive than CT at detecting AiDS-related abnormalities (7). Other AIDS-related opportunistic infections are also more readily detected by MRI than CT. MR scans of patients with Cryptococcus neoformans can identify mass lesions (cryptococcoma), mihary disease, leptomeningeal nodules, and distention of Virchow-Robin spaces. Up to 50% of HIV patients will develop spinal cord infections with cytomegalovirus and herpes simplex virus. These infections can cause abnormal enhancement on CT and MR scans, although MRI is usually more sensitive. Bacterial infectious in the brain can manifest through meningeal involvement that can be detected by meningeal enhancement on CT- and MR-enhanced scans. Infectious aneurysms associated with meningitis, bacterial endocarditis, or fungal infection can be detected by angiographic studies. In patients not undergoing surgery, repeated studies are usually required to follow the progress of such lesions (8). Brain abscesses are

NOTIg: No n~spousibility is assumed by the Publisher for any injury and/or damage to pemorm or propmty as a matter of products liability, negligence or otherwise, or from any me or operation of aay methods, products, instructions or ideas contained in the mate~al bemin. No enuested test or prcoedme should be carried oat unless, in the reader's judgment, its risk is justified. Became of rapid advances in medical sciences, w e recommend th~ the independ•t verification of diagnoses end drag dosages should be made. Discussions, views, and recommendations as to medical procedures, choice o f d m ~ and dm8 dosages arc the responsibility of the authors.

Ch'~cal Microbwlogy Nm,e/ctl~" (ISSN 0196-4399) is issued twice monthly in one indexed volume per year by Elsevi~ Science Inc., 655 Avenue of the Americas, New York, NY 10010. Sub~ription pt~e per year:. $155.00 including p~tage rout handling in the United States, Cmmde, and Mexico. Add $59.00 for pcetage in the rest of the world. Scared-chum pmtMe paid at New York, NY and at additional mailing o f f i ~ . Postmaster:. Send address changes to Cfinicai Microblolo&yNewMef;er,Elsevier Science Inc., 655 Avenue of the Americas, New York, NY 10010.

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Clinical Microbiology Newsletter 16:1,1994

readily identified on both CT and MRI scans. On CT they show a hypodense center with smooth thin walls that strongly enhance after adminisW~on of intravenous contrast Metastatic disease and lymphoma can give similar appearances. Indium-I I 1-1abeled white cell scans have been shown to have a high degree of specificity for the detection of brain abscesses and can be performed when a differentiation of abscess from neoplasm cannot be made by either CT or MRI. Use of enhanced CT in the evaluation of tuberculosis of the brain has identified meningeal involvement in 18% of cases, pure parenchymal involvement in 71%, and mixed meningeal involvement in 1 I% (9). Parenchymal tuberculosis can be subdivided into parenchymai and granulomatons disease and tuberculous abscess. The former is more common and is characterized by edema surrounding an area of ring enhancement with irregular walls on intravenous contrast-enhanced CT or by solid enhancement. Tuberculous abscesses, which can be single or multiloculated, have alvemances identical to pyogenic abscesses on CT scans. Parasitic infections, such as neurocysticercosis, may show enhancement on M R imaging (Figure 1) following gadolinium administration,with edema identifiedon T2-weighted images. Larva thatare stillalivedo not produce a host reaction,produce littleedema, and in generaldo not enhance. M R has been shown to be more sensitivethan C T scanning at detectingamebic (Entamoeba histolytica)infectionwith thickwalled enhancement in some patients and nodular enhancement in others. CT and MRI studies can detect fungal infections, including aspergillosis, blastomycosis, and histoplasmosis. The appeara n o n , h o w e v e r , a r e US~mlly n o n s p e c i f i c .

The Chest The mainstay for detecting infection within the chest is still the chest x ray. Plain radiographs identify most disease processes, including pneumonia, lung abscess, empyema, and med_~inal abscess. The hallmark of exudative infections in the chest x ray is air-space disease chaxaeterized by bronchi outlined by opacified alveoli f'dled with Clinical MicrobiologyNewsletter 16:1,1994

Figure 1.Axial MRI of the head. This demonstrates multiple lesions throughout the brain (arrow) in a patient with diffuse headache. These lesions were a result of toxoplasmosis.

exudative material. However, other disease processes such as pulmonary edema and lymphoma can produce similax appearances and therefore the findings must be taken in clinical context. Although CT is more sensitive than the chest x ray in identifying air-space disease, the patient will usually present after readily identifmble changes are visualized on the chest x ray. However, some opportunistic infections may present with nonspecific clinical disease and without overt changes on the chest x ray. In these circumstances, a Cl" scan of the chest, although not routinely indicated, may identify changes not vlsnaliTed by chest x ray, including airspace disease, "ground glass" appearances, an interstitial pattern, and a "patchwork pattern" of air-space and interstitial disease (10). CT can provide additional informa© 1994 Elsevier Science Inc.

tion beyond plain radiography in the evaluation of lung abscess. These include delineation of pleural-abscess relationships, characterization of paxenchymal consolidation, visualization of internal contents of the abscess, improved visualization of vessels, and enhanced resolution of these abnormalities. CT is of particular benefit in differentiating lung abscess from empyema. Abscesses tend to be round and demonstrate thick, irregular walls. Bronchi and pulmonary vessels terminate abruptly at the advancing wall of an abscess and are not compressed or distorted (11). Empyemas, in contrast, have lenticular shapes surrounded by a fibrin peel that forms the basis for the most reliable radiographic feature of an empyema, which has been called the "split pleura" (11) sign. Radionnclide studies age generally 01964399/94/$0.1)0 + O6.OO

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Figure 2. Axial CT scan of the lower pelvis demonstrating an abscess posteriorly (arrow). This patient had undergone an abd~maino-perineal resection 6 d previously and now presented with recurrent fever.

not helpful in detecting lung infection but are particularly useful in the evaluation of acute diffuse pneumonia such as Pneumocystis carinii infection. This and other opportunistic infections may cause either focal or diffuse uptake in the lung. The chest x ray is normal in the early stages at a time that gallium scanning reveals profound disease. An abnormal gallium scan in an immunocompromised patient with pulmonary symptoms is good evidence for infection. Unfortunately, this may not be sufficient information to institute treatment because there are many potentially pathogenic microorganisms, each of which requires a different antlmicrobial regimen. Additional diagnostic studies such as bronchoscopy are often necessary. Ultrasound, although of no benefit for parenchymal lung disease, readily identifies pleural collections resulting from pneumonia. Ultrasound is ideal for providing image-guidance needle aspiration when secondary infection of a Imrapneumonic effusion is suspected. CT further defines the extent of empyema and is usually required for follow-up observation after surgical or radiologic drainage. The Abdomen Plain films of the abdomen can suggest the location of an abscess in up to 50% of cases (12). These films may be

of less value in the immediate post-op-

erative period if a paralytic ileus with excessive bowel gas creates confusing patterns. The cardinal plain film feature of an abscess is an extraluminal, abnormal gas collection. Less common findings include reactive pleural effusion or elevation of the diaphragm or a mass may be detected if it causes displacement of adjacent bowel loops. However, many of these signs may be appreciated only in retrospect. In addition, once an abscess is identified, further imaging studies are usually required to def'me it more clearly. A contrast study is particularly useful in detecting a suspected abscess that has originated from a perforation of the gasIlointestinal tract. Studies must usually be performed with water-soluble contrast media rather than barium because extravasation of barium is higMy toxic to the peritoneum, with up to a 50% mortality resulting from barium-induced peritonitis. Furthermore, barium will degrade subsequent CT examinations whose result is probably more useful than that of the contrast study. Ultrasound is of particular benefit in the evaluation of abdominal abscesses in the upper abdomen and pelvis where air-filled bowel is less likely to attenuate the sound beam. The liver provides a window for the evaluation of intrahepatic, perihepatic, and subphrenic fluid collections. Similar appearances can be identified in the spleen. The kid-

neys can be clearly identified using the liver or spleen as windows and anatomic changes resulting from abscess formation can be identif~L In the mid-abdomen, ultrasound is generally effective only if an abscess cavity lies against the abdominal wall. In the pelvis the urine-filled bladder provides an ideal sonic window with over 90% sensitivity for the detection of pelvic abscesses (13). Abscesses generally appear as round or oval fluid collections that are generally hypoechoeic but frequently contain internal echoes, although the pattern may range from completely anechoeic to highly echogenic (2). Gas-filled abscesses may be difficult to identify, although abscesses that contain multiple small bubbles will be identified as multiple small echogenic foci, creating a coarse echogenic pnttern. The apIrarance of an abscess on ultrasound is nonspecific because any fluid collection within the abdomen could give similar appearances. Therefore, as with all radiologic tests, detected abnormalities should be correlated with clinical findings. CT is the primary modality for abscess detection within the abdomen, with reported sensitivity over 95% (2). The CT scan (Figure 2) must be planned and conducted so that it will provide the diagnostic information required. The bowel must be opacified with oral/rectal contrast because

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Clinical Microbiology Newsletter 16:1,1994

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unopacified bowel can have an appearance similar to that of an abscess. Additional information may be acquired because the CT scan images the entire abdomen, including soft tissues and bone. The CT signs of an abscess include a well-defined area of low attenuation, obliteration of surrounding fat planes, extraluminal gas collections, and displacement of surrounding viscera (2). Infection without abscess formarion can be identified as an area of edema within the fat planes, which is more specific if localized to an area of suspected infection. Occasionally, administration of intravenous contrast may increase the sensitivity for abscess detection by delineating an enhancing rim to an abscess due to the intense vascular supply to the wall of the abscess. Radionuclide imaging in the abdomen plays a role only when other imaging m~aliries fail to show an abnormality. Gallium scanning, which detects most significant abdominal collections, is nonspecitic and is readily excreted into normal bowel. Administration of indium-11 l-labeled leukocytes has an advantage because they are not norreally excreted into the bowel. Other than that of the liver or spleen, there should be no activity within the normal abdomen or pelvis. After CT scanning, indium-11 I-labeled leukocyte imaging is probably the radiologic investigation of choice for the detection of an occult abdominal infection (Figure 3).

The Muscuioskeletal System Plain films are us~mlly the initial diagnostic study used for the investigation of osteomyeliris. If deep, soft tissue swelling, periosteal reaction, cortical irregularities, and demineralization saggest osteomyelitis, additional studies may not be required. However, it may be 3 to 4 wk before plain films show evidence of disease, by which rime extensive destruction may have occurred. Therefore, if clinical suspicion of acute osteomyelitis is present, additional imaging tests will be required. CT can demonstrate almormalities earlier than plain bone films and is particularly useful in the spine, pelvis, and sternum, which are difficult to visnalize on the plain film. Early findings include increased marrow density and surround-

Clinical MierobiololD' Newsletter 16:1,1994

Figure 3. Radionucleide study showing an abscessin the right lower quadrant (arrow) in a patient with Crohn's disease.

ing soft tissue edema. Chronic osteomyelitis shows sclerosis, demineralization, periosteal reaction, and sequesca (14). However, as with plain films, the diagnosis of active infection is difficult or impossible with CT. MRI is inherently more sensitive than CT for marrow and soft tissue abnormalities. Active osteomyelitis is identified by a decreased signal on Tl-weighted images and a bright or increased signal on T2-weighted images, which represents replacement of marrow fat with water secondary to edema, exudate, hyperemia, and ischemia (14). Findings on MRI appear much earlier in the course of the disease than on CT or plain films and reported sensitivities approach 95% (15). MRI is of particular value in examining the spine where osteomyelitis shows a characteristic pattern of conflu-

© 1994 Elsevier Science Inc.

ent vertebral body and disk involvement. However, MRI signal characteristics that reflect osteomyeliris are intrinsically nonspecif'lc as tumors, fractures, and a variety of inCa- or extramedullary inflammatory processes can show similar appearances (14). In addition, the diagnostic sensitivity of MRI is fimited by the presence of a metal prosthesis and is a cosily technique. For these reasons, the initial diagnostic imaging study may remain the conventional planar bone scan. The overall sensitivity of conventional bone scan performed with injected 99~Technetium-MDP approaches 100% (14) and most nuclear medicine practitioners would argue that a negative bone scan in an otherwise healthy adult essentially rules out bone infection. A conventional bone scan is the first radiologic test that will detect evidence of osteomyelitis, often within the first few days of the disease. With the recent addition of single photon emission computed tomography (SPECT) imaging, it is possible to image in the axial plane, similar to a CT scan, which therefore improves spatial resolution and may increase sensitivity. Classically, osteomyelitis presents as a region of increased blood flow and appears as an area of increased tracer activity on initial blood flow (dynamic) and on delayed (equilibrium) images. Photopenic defects are less common but may represent osteomyelitis, particularly in the early stages. Positive bone scans, although extremely sensitive, are relatively nonspecific, and thus gallium scanning and indium-111 scanning are sometimes used. There is tittle normal white cell accumulation in noninflammatory regions of increased bone turuover. This contrasts sharply with gallium imaging and lxovides a real advantage in patients with complicated orthopedic problems. Indium- 111 scanning is therefore more commonly applied in the search for osteomyeliris in previously traumatized bone and adjacent to joint prostheses. Indium-leukocyte scanning is also useful in the evaluation of celluliris and suspected soft tissue abscesses and is useful to distinguish between cellulitis alone and osteomyelitis with overlying soft tissue

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infection. This is a common problem in the diabetic foot, particularly in regions overlying neurolmthic joints. Unfortunately, the limitations of s ~ ' a l resolution may obscure the distinction between bone and soft tissue and correlation with conventional radiographic studies and clinical findings are required.

Conclusion A variety of radioiogic tests are available to the physician for the diagnosis and follow-up of infection. Each tests has its merits and limitations and should be tailored to the diagnosis in question. Abnormal findings are often nonspecific and should always be correlated with clinical disease. Recent advances in radiologic technology have improved the sensitivity for detection of disease but problems of cost, r~iiation dosages, and availability continue to limit their applicability. For these reasons, the plain radiograph will continue to be the initial radiologic examination in most cases. Further imaging should be performed if the plain film identifies a nonspecific abnormality or if the clinical index of suspicion is high.

References 1. Mayo, J. R., S. A. Jackson, and N. L. Muller. 1993. High resolution CT of the chest: radiation dose. AJR 160:479-481. 2. Gerzof, S. G. and M. E. Oates. 1988. Imaging techniques for infections in the surgical patient. Surg. Clin. North Am. 68:147-165. 3. Palmer, E. L., J. A. Scott, and H. W. Strauss. 1992. Chapter 9, p. 343-364. In: Practical nuclear medicine. 1st edition. WB Saunders Company, Philadelphia. 4. Post, M. J. D., J. R. B~ger, and R. M. Quencer 1991. Asymptomatic and neurologically symptomatic HlV-positive individuals: prospective evaluation with cranial MR imaging. Radiology 178:131-139. 5. MoeUer,A. A. and H. C. Backmund. 1990. Ventricle brain ratio in the clinical course of HIV infection. Acta Neurol. Scand. 42:164-165. 6. Rauch, R. A., C. Bazan, and J. R. Jinkins. 1992. Imaging of infections of the central nervous system. Curr. Opin. Radiol. 4:43-51. 7. McArthur, J. C. et al. 1989. Low prevalence of neurological and neuropsychological abnormalities in otherwise healthy HIV-I infection: association with AIDS-related complex but not asymptomatic HIV-1 infection. Ann.

Neurol. 26:582--600. 8. Barrow, D. L. and A. R. Prats. 1990. Infectious intracranial aneurysms: comparison of groups with and without endocarditis. Neurosurgery 27:562-573. 9. Jinkins, J. R. 1991. Computed tomography of intracranial tuberculosis. Neuroradiology 33:126-135. 10. Kuhlman, J. E. et al. 1990. Pnewnocystis carinii pneumonia: spectrum of parenchymal CT findings. Radiology 175:711-714. 11. Stark, D. D., M. P. Federle, and P. C. Goodman. 1983. Differentiating lung abscess and empyema: radiography and computed tomography. AJR 141:163-167. 12. Conneil, T. R. et al. 1980. Upper abdominal abscesses: a continuing and deadly problem. AJR 134:759-765. 13. Taylor, K. J. W. et al. 1980. Accuracy of gray scale ultrasound diagnosis of abdominal and pelvic abscesses in 220 patients. Lancet 1:83-84. 14. Wegener, W. A. and A. Alavi. 1991. Diagnostic imaging of musculoskeletal infection.Orthoped. Clin. North Am. 22:401-418. 15. Schauwecker, D. S., Braunstein, and E. M., L. J. Wheat. 1990. Diagnosticimaging of ostcomyelitis. Infect. Dis. Clin. North Am. 4:441-463.

Case Report

Bacteremia Caused by Tsukamurella Species Carla Clausen, Ph.D. Department of Laboratories Children's Hospital and Medical Center Seattle, WA 98105 Carolyn K. Wallis, R.M.(AAM) Department of Laboratory Medicine Harborview Medical Center University of Washington, Seattle, WA 98104 The patient, a 5-yr-old female, had received an muelatod bone marrow transplant 5 mo after a diagnosis of

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acute myelogenous leukemia. Her clinical course after transplantation was complicated by graft versus host disease and cytomegalovirus (CMV) gastroenteritis. After discharge from the hospital, her health had been stable for about 2 mo when she developed fever, nausea, vomiting, diarrhea,and abdominal pain. Her private physician obtained blood for culture~ h the Hicknum catheter and began treatment with oral ~-suifamethoxazole (TMP-

S M Z ) . Her symptoms persisted over the next 2 d and she was therefore admitted to the hospital. On admission, the patient had a temperature of 39.5"C, a while blood count of 5700/ram 3 with 7% p o l e clear leukocyte, and slisht toxic granulation. Blood for cullme was drawn through a periphend vein, and empirical

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Clinical Microbiology~ r

treatment with ceftazadime and gentamicin was begun. Later on the day of admission, a report was received that

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