- Email: [email protected]
Rocky mountain spotted fever in siblings
tion and attainment of the desired serum levels. Included here are drug-induced achlorhydria associated with concomitant antacids, anticholinergics and Hrblockers. It has been our
experience that inadequate ketoconazole serum levels may be observed in up to 2507o of specimens tested. Thus, monitoring of ketoconazole serum levels (2-hr peak values) may be a necessary adjunct
to insure maximum clinical efficacy. However, since we do not know what ketoconazole MICs mean, a ketoconazole assay at this time can only be regarded as a measure of patient compliance.
was 140 beats per minute, blood pressure 90/70 mm Hg, temperature 39.2°C, and respirations 32 per minute. In addition to the maculopapular rash, which was petechial in the right axilla and on the dorsum of the right foot, there was a 2-mm healing eschar in the left groin where she had been "bitten by something." Laboratory data included platelets 55,000//~1 and WBC I0, 400//A with 76°/o bands and 11% PMNs. A skin biopsy was demonstrated to contain numerous Rickettsia rickettsit in dermal blood vessels by specific direct immunofluorescence on frozen sections. This result confirmed the diagnosis of RMSF from a differential diagnosis that had also included meningococcemia, Coxsackie and ECHO viral infections, other viral encephalitides, toxoplasmosis, Reye's syndrome, and toxic ingestion. The patient was treated with intravenous chloramphenicol and subsequently underwent a severe hospital course with a moderate consumption coagulopathy, severe edema of the entire body, dermal bullae and necrosis of the dorsum of the feet, lactic acidosis, mild oliguric acute renal failure, and hypoxemia secondary to moderately severe pulmonary edema on diuresis. Management required fresh frozen plasma, packed red blood cells, intravenous hydrocortisone and oxygen. Serologic studies showed Proteus OX-19 agglutination titer rising from 1:80 on admission to >1:1280 34 days after onset of symptoms, and Proteus OX-2 titer rising from 1:40 to 1:320. RMSF latex agglutination titers were intially < 1:16 and rose to a titer of 1:512 after
three weeks. Microimmunofluorescence (Micro-IF) with antiwhole human serum was 1:64 (control was 1:8).
C a s e Reports
Rocky Mountain Spoiled Fever in Siblings Susan E. Cancelosi, Ph.D. David Walker, M.D. James D. Folds, Ph.D. Clinical Immunology Laboratory Division of Laboratory Medicine North Carolina Memorial Hospital University of North Carolina Chapel Hill, North Carolina 27514 An occurrence of the acute disease Rocky Mountain spotted fever (RMSF) involving two members of a family is discussed here. The disease is caused by the intracellular bacterium Rickettsia rickettsii and is transmitted by the bite of an infected tick. The diagnostic procedures used here have been reviewed elsewhere (1, 2).
Patten! 1 A seven-year old black girl presented to her local physician five days prior to hospitalization with fever (39.4 ° C), nausea, vomiting, and headache. When treatment for two days with a laxative produced no improvement, she was given cloxacillin, promethazine hydrochloride, and acetaminophen. When referred to a hospital on her fifth day of symptoms, she had a maculopapular rash over her entire body including the palms and soles. She was transferred to North Carolina Memorial Hospital (NCMH) following an evaluation that included normal CSF glucose and protein concentration with no cells, and negative countercurrent immunoelectrophoresis for antigens of Haemophihts influenzae, Neisseria meningitidis, streptococci, and Streptococcus pneumoniae. On admission she appeared disoriented and dehydrated. Her pulse
Copyright © 1982 by G. K. ttall& Co.
Patient 2 A 15-year old sister of Patient 1 was seen at NCMH two days after her sibling's hospitalization. She had been ill with headache and fever for three days and with a rash for one day. She denied vomiting, diarrhea, and myalgia but noted exposure to ticks. Physical examination revealed a temperature of 40.0 °C and a maculopapular rash involving the arms, legs, palms, and soles, with few acral petechiae. Laboratory data included platelets 180,000/pl, WBC 7,900/pl with 23070 bands, 45°70 PMNs, 23°7o lymphocytes, 6% atypical lymphocytes, 2°7o monocytes, and l°T0 eosinophils. The diagnosis of'RMSF was confirmed by punch biopsies of petechial lesions of the left arm shown to contain R. rickettsii by rapid immunofluorescent demonstration~ Because of her mild disease she was managed as an outpatient and responded to oral tetracycline treatment. Serum collected on a clinic visit two days later showed Proteus OX-19 and OX-2 agglutination titers of 1:160 and 1:80, respectively. The initial latex agglutination titer was 1:16 and the Micro-IF titer was 1:32. RMSF is rapidly fatal in a large number of untreated cases; thus it is necessary to diagnose and begin treatment early. However, since the symptoms are confused with a number of other bacterial and viral infections (as indicated in the report of Patient 1), this disease is difficult
29
to diagnose (3). The classic clinical feature o f RMSF is a petechial rash that begins on the extremities, including the palms and soles, and eventually spreads to the trunk. The traditional serologic tests for RMSF, the Weil-Felix and complement fixation tests, are probably the least sensitive diagnostic procedures, and since the accurate interpretation of the results obtained with these tests requires the demonstration of a change in titer, they are most useful in confirming an established diagnosis only. Micro-IF is quite sensitive and, when coupled with antihuman IgG or IgM, may be useful in differentiating the stage o f the disease. Indirect hemagglutination assay (IHA) is perhaps the most sensitive serologic technique and may give the earliest positive result. The easiest serologic test to perform is the latex agglutination procedure, although it is not quite as sensitive as the IHA. Finally, the direct immunofluorescent test on biopsy specimens is sensitive and can detect organisms once the rash has appeared. However, because of the difficulty of identifying organisms in patients already treated with antibiotics, it is advisable to use a serologic test in conjunction with this test (2).
References 1. Kleeman, K. T. 1980. Diagnosis of Rocky Mountain spotted fever. Clin. Microbiol. Newsl. 2(I 7): 1-3. 2. Walker, D. H., B. G. Cain, and P. M. Olmstead. 1978. Laboratory diagnosis of Rocky Mountain spotted fever by immunofluorescent demonstration of Rickettsia rickettsii in cutaneous lesions. Am. J. Clin. Pathol. 69:619-623. 3. Youmans, G. P. 1980. Rickettsial diseases, pp. 681-691. hz G. P. Youmans, P. Y. Paterson, and H. M. Sommers (eds.), The biologic and clinical basis of infectious diseases. W. B. Saunders, Philadelphia, Pa.
30
Septic S h o c k D u e to Enterobacter sakazakii E. Boquet Jim~nez, Ph.D. Professor of Microbiology University of Barcelona, Barcelona, Spain C. Romeu Gim~nez, Ph.D. Hospitalary Center of Manresa Manresa, Spain A 76-year-old male entered the hospital on May 25, 1980. He suffered from urinary retention, and urine was obtained by transurethral catheterization by his family doctor. The patient had had surgery 1 ½ years previously for rectal adenocarcinoma. He had also had l u m b o sacral aches for several months, but there was no apparent metastasis. At the time of entering the hospital he appeared to be in shock, with low blood pressure and respiratory alkalosis. Serum urea and creatinine were increased, and he had a leukocytosis with a shift to the left. He had no fever. Urine and blood cultures were taken immediately, and the patient was treated with ampicillin and gentamicin. Subsequently Enterobacter sakazakii was isolated from urine and blood. E. sakazak# is a relatively new species that is not included in the eighth edition of Bergey's Manual o f Determ#1ative Bacteriology (4). It has been shown to differ from Enterobacter cloacae and Enterobacter aerogenes by the use o f genetic techniques. To date there are very few cases reported of diseases caused by this microorganism (2, 3, 6). The identification was carried out by using the API 20-E system and was confirmed with the methods o f Brenner et al. (1). The organism had a yellow pigment, was DNase-positive, D-sorbitol-negative, lysine decarboxylase-negative, arginine dihydrolase-positive, and ornithine
decarboxylase-positive. Reading of tests was done within 48 hours at 36°C in all the cases, except for the yellow pigment (room temperature, 48 hours) and DNase toluidine blue (36°C, 5 days). Antibiotic susceptibility testing was performed using the Autobac system (Pfizer) and by disc diffusion techniques. In both systems the organism was susceptible to gentamicin, ampicillin, tetracycline, tobramycin, amikacin, cotrimoxazole, colistin, nitrofurantoin, and nalidixic acid. It was resistant to cephalothin and cefoxitin. With ampicillin and gentamicin therapy, the patient responded favorably and gradually improved. He recovered both clinically and microbiologically within 4 days.
References 1. Brenner, D. J., et al. 1977. Taxonomic and nomenclature changes in Enterobacteriaceae. HEW (CDC) 78-8356. Centers for Disease Control, Atlanta, Ga. 2 . MonroG P. W., and W. L. Tift. 1979. Bacteremia associated with Enterobacter sakazakii (yellowpigmented Enterobacter cloacae). J. Clin Microbiol. 10:850-860. 3 . Nissen, R., T. Norholm, and K. E. Sibon|. 1965. A case of neonatal meningitis caused by a yellow Enterobacter. Dan. Med. Bull. 12:128-130. 4. Sakazaki, R. 1974. Enterobacter cloacae, p. 325. In R. E. Buchanan and N. E. Gibbons (eds.), Bergey's manual of determinative bacteriology, 8th ed. The Williams, and Wilkins Co., Baltimore. 5 . Steigerwait, A. G., et al. 1976. DNA relatedness among species of Enterobacter and Serratia. Can. J. Microbiol. 22:121-137. 6 . Urmenyi, A. M. C., and A. W. Franklin. 1961. Neonatal death from pigmented coliform infection. Lancet i:313-315.
ClinicalMicrobiologyNewsletter
experience that inadequate ketoconazole serum levels may be observed in up to 2507o of specimens tested. Thus, monitoring of ketoconazole serum levels (2-hr peak values) may be a necessary adjunct
to insure maximum clinical efficacy. However, since we do not know what ketoconazole MICs mean, a ketoconazole assay at this time can only be regarded as a measure of patient compliance.
was 140 beats per minute, blood pressure 90/70 mm Hg, temperature 39.2°C, and respirations 32 per minute. In addition to the maculopapular rash, which was petechial in the right axilla and on the dorsum of the right foot, there was a 2-mm healing eschar in the left groin where she had been "bitten by something." Laboratory data included platelets 55,000//~1 and WBC I0, 400//A with 76°/o bands and 11% PMNs. A skin biopsy was demonstrated to contain numerous Rickettsia rickettsit in dermal blood vessels by specific direct immunofluorescence on frozen sections. This result confirmed the diagnosis of RMSF from a differential diagnosis that had also included meningococcemia, Coxsackie and ECHO viral infections, other viral encephalitides, toxoplasmosis, Reye's syndrome, and toxic ingestion. The patient was treated with intravenous chloramphenicol and subsequently underwent a severe hospital course with a moderate consumption coagulopathy, severe edema of the entire body, dermal bullae and necrosis of the dorsum of the feet, lactic acidosis, mild oliguric acute renal failure, and hypoxemia secondary to moderately severe pulmonary edema on diuresis. Management required fresh frozen plasma, packed red blood cells, intravenous hydrocortisone and oxygen. Serologic studies showed Proteus OX-19 agglutination titer rising from 1:80 on admission to >1:1280 34 days after onset of symptoms, and Proteus OX-2 titer rising from 1:40 to 1:320. RMSF latex agglutination titers were intially < 1:16 and rose to a titer of 1:512 after
three weeks. Microimmunofluorescence (Micro-IF) with antiwhole human serum was 1:64 (control was 1:8).
C a s e Reports
Rocky Mountain Spoiled Fever in Siblings Susan E. Cancelosi, Ph.D. David Walker, M.D. James D. Folds, Ph.D. Clinical Immunology Laboratory Division of Laboratory Medicine North Carolina Memorial Hospital University of North Carolina Chapel Hill, North Carolina 27514 An occurrence of the acute disease Rocky Mountain spotted fever (RMSF) involving two members of a family is discussed here. The disease is caused by the intracellular bacterium Rickettsia rickettsii and is transmitted by the bite of an infected tick. The diagnostic procedures used here have been reviewed elsewhere (1, 2).
Patten! 1 A seven-year old black girl presented to her local physician five days prior to hospitalization with fever (39.4 ° C), nausea, vomiting, and headache. When treatment for two days with a laxative produced no improvement, she was given cloxacillin, promethazine hydrochloride, and acetaminophen. When referred to a hospital on her fifth day of symptoms, she had a maculopapular rash over her entire body including the palms and soles. She was transferred to North Carolina Memorial Hospital (NCMH) following an evaluation that included normal CSF glucose and protein concentration with no cells, and negative countercurrent immunoelectrophoresis for antigens of Haemophihts influenzae, Neisseria meningitidis, streptococci, and Streptococcus pneumoniae. On admission she appeared disoriented and dehydrated. Her pulse
Copyright © 1982 by G. K. ttall& Co.
Patient 2 A 15-year old sister of Patient 1 was seen at NCMH two days after her sibling's hospitalization. She had been ill with headache and fever for three days and with a rash for one day. She denied vomiting, diarrhea, and myalgia but noted exposure to ticks. Physical examination revealed a temperature of 40.0 °C and a maculopapular rash involving the arms, legs, palms, and soles, with few acral petechiae. Laboratory data included platelets 180,000/pl, WBC 7,900/pl with 23070 bands, 45°70 PMNs, 23°7o lymphocytes, 6% atypical lymphocytes, 2°7o monocytes, and l°T0 eosinophils. The diagnosis of'RMSF was confirmed by punch biopsies of petechial lesions of the left arm shown to contain R. rickettsii by rapid immunofluorescent demonstration~ Because of her mild disease she was managed as an outpatient and responded to oral tetracycline treatment. Serum collected on a clinic visit two days later showed Proteus OX-19 and OX-2 agglutination titers of 1:160 and 1:80, respectively. The initial latex agglutination titer was 1:16 and the Micro-IF titer was 1:32. RMSF is rapidly fatal in a large number of untreated cases; thus it is necessary to diagnose and begin treatment early. However, since the symptoms are confused with a number of other bacterial and viral infections (as indicated in the report of Patient 1), this disease is difficult
29
to diagnose (3). The classic clinical feature o f RMSF is a petechial rash that begins on the extremities, including the palms and soles, and eventually spreads to the trunk. The traditional serologic tests for RMSF, the Weil-Felix and complement fixation tests, are probably the least sensitive diagnostic procedures, and since the accurate interpretation of the results obtained with these tests requires the demonstration of a change in titer, they are most useful in confirming an established diagnosis only. Micro-IF is quite sensitive and, when coupled with antihuman IgG or IgM, may be useful in differentiating the stage o f the disease. Indirect hemagglutination assay (IHA) is perhaps the most sensitive serologic technique and may give the earliest positive result. The easiest serologic test to perform is the latex agglutination procedure, although it is not quite as sensitive as the IHA. Finally, the direct immunofluorescent test on biopsy specimens is sensitive and can detect organisms once the rash has appeared. However, because of the difficulty of identifying organisms in patients already treated with antibiotics, it is advisable to use a serologic test in conjunction with this test (2).
References 1. Kleeman, K. T. 1980. Diagnosis of Rocky Mountain spotted fever. Clin. Microbiol. Newsl. 2(I 7): 1-3. 2. Walker, D. H., B. G. Cain, and P. M. Olmstead. 1978. Laboratory diagnosis of Rocky Mountain spotted fever by immunofluorescent demonstration of Rickettsia rickettsii in cutaneous lesions. Am. J. Clin. Pathol. 69:619-623. 3. Youmans, G. P. 1980. Rickettsial diseases, pp. 681-691. hz G. P. Youmans, P. Y. Paterson, and H. M. Sommers (eds.), The biologic and clinical basis of infectious diseases. W. B. Saunders, Philadelphia, Pa.
30
Septic S h o c k D u e to Enterobacter sakazakii E. Boquet Jim~nez, Ph.D. Professor of Microbiology University of Barcelona, Barcelona, Spain C. Romeu Gim~nez, Ph.D. Hospitalary Center of Manresa Manresa, Spain A 76-year-old male entered the hospital on May 25, 1980. He suffered from urinary retention, and urine was obtained by transurethral catheterization by his family doctor. The patient had had surgery 1 ½ years previously for rectal adenocarcinoma. He had also had l u m b o sacral aches for several months, but there was no apparent metastasis. At the time of entering the hospital he appeared to be in shock, with low blood pressure and respiratory alkalosis. Serum urea and creatinine were increased, and he had a leukocytosis with a shift to the left. He had no fever. Urine and blood cultures were taken immediately, and the patient was treated with ampicillin and gentamicin. Subsequently Enterobacter sakazakii was isolated from urine and blood. E. sakazak# is a relatively new species that is not included in the eighth edition of Bergey's Manual o f Determ#1ative Bacteriology (4). It has been shown to differ from Enterobacter cloacae and Enterobacter aerogenes by the use o f genetic techniques. To date there are very few cases reported of diseases caused by this microorganism (2, 3, 6). The identification was carried out by using the API 20-E system and was confirmed with the methods o f Brenner et al. (1). The organism had a yellow pigment, was DNase-positive, D-sorbitol-negative, lysine decarboxylase-negative, arginine dihydrolase-positive, and ornithine
decarboxylase-positive. Reading of tests was done within 48 hours at 36°C in all the cases, except for the yellow pigment (room temperature, 48 hours) and DNase toluidine blue (36°C, 5 days). Antibiotic susceptibility testing was performed using the Autobac system (Pfizer) and by disc diffusion techniques. In both systems the organism was susceptible to gentamicin, ampicillin, tetracycline, tobramycin, amikacin, cotrimoxazole, colistin, nitrofurantoin, and nalidixic acid. It was resistant to cephalothin and cefoxitin. With ampicillin and gentamicin therapy, the patient responded favorably and gradually improved. He recovered both clinically and microbiologically within 4 days.
References 1. Brenner, D. J., et al. 1977. Taxonomic and nomenclature changes in Enterobacteriaceae. HEW (CDC) 78-8356. Centers for Disease Control, Atlanta, Ga. 2 . MonroG P. W., and W. L. Tift. 1979. Bacteremia associated with Enterobacter sakazakii (yellowpigmented Enterobacter cloacae). J. Clin Microbiol. 10:850-860. 3 . Nissen, R., T. Norholm, and K. E. Sibon|. 1965. A case of neonatal meningitis caused by a yellow Enterobacter. Dan. Med. Bull. 12:128-130. 4. Sakazaki, R. 1974. Enterobacter cloacae, p. 325. In R. E. Buchanan and N. E. Gibbons (eds.), Bergey's manual of determinative bacteriology, 8th ed. The Williams, and Wilkins Co., Baltimore. 5 . Steigerwait, A. G., et al. 1976. DNA relatedness among species of Enterobacter and Serratia. Can. J. Microbiol. 22:121-137. 6 . Urmenyi, A. M. C., and A. W. Franklin. 1961. Neonatal death from pigmented coliform infection. Lancet i:313-315.
ClinicalMicrobiologyNewsletter