美国医生怎么治猫咬伤后发热？

case records of the massachusetts general hospital T h e n e w e ngl a nd j o u r na l o f m e dic i n e n engl j med 363;16 nejm.org october 14, 20101560 Founded by Richard C. Cabot Nancy Lee Harris, m.d., Editor Eric S. Rosenberg, m.d., Associate Editor Jo-Anne O. Shepard, m.d., Associate Editor Alice M. Cort, m.d., Associate Editor Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor From the Division of Infectious Disease, Department of Medicine (A.N.W.), and the Department of Pathology (J.A.B.), Massa- chusetts General Hospital; and the Depart- ments of Medicine (A.N.W.) and Pathology (J.A.B.), Harvard Medical School — both in Boston. N Engl J Med 2010;363:1560-8. Copyright © 2010 Massachusetts Medical Society. Pr esen tation of C a se Dr. Allyson K. Bloom (Infectious Disease): A 29-year-old woman was admitted to the hospital because of fever after a cat bite. The patient had been well until 5 days before admission, when, while working as a veterinarian’s assistant at an animal hospital, she was bitten on the right thenar eminence by a domesticated cat, sustaining a single puncture wound. The cat, which had received rabies vaccinations in the past, had disappeared from its home for several days and had returned febrile, jaundiced, and anemic. After being bitten, the patient washed the wound and took one dose of amoxicillin, according to workplace protocol. She continued to work that day and handled cats, rabbits, guinea pigs, and dogs (including a dog with elevated results of liver-function tests and a history of leptospirosis). During the next 4 days, the patient cleaned cages, handled animals, and petted horses, sheep, and unvaccinated “barn cats” outside. She did not report that any animal licked her wound. The day before admission, swelling, erythema, and pain developed over the volar radial surface of the patient’s hand. The same day, the cat was euthanized because of progressive illness, and a specimen of the brain was sent for rabies testing. The next morning, throbbing pain developed in the patient’s hand. She went to another hospital, where she rated the pain at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. On examination, the vital signs were normal. The thenar eminence was red, hot, and swollen, with evidence of a small puncture wound; the range of motion of the joints was full, without pain, and there was no fluctuance. Ampicillin–sulbactam was given intravenously, and immunizations for diphtheria, tetanus, and pertussis were administered intramuscularly. Amoxicil- lin–clavulanic acid and oxycodone were prescribed, and the patient was discharged 2 hours after presentation, with instructions to follow up the next day, or sooner if the condition worsened. Approximately 9 hours later, she returned to the other hospital because of increasing pain (rated at 10 of 10) and swelling of the hand, difficulty moving her wrist, malaise, chills, neck pain, swollen lymph nodes, and subjective fever. On examination, the temperature was 37.7°C; other vital signs were normal. There was 1+ nonpitting edema on the right arm; edema and ery- thema were present over the thenar eminence, with proximal streaking and in- creased warmth. Range of motion at the wrist was normal. Right axillary lymph- Case 31-2010: A 29-Year-Old Woman with Fever after a Cat Bite Arnold N. Weinberg, M.D., and John A. Branda, M.D. The New England Journal of Medicine Downloaded from www.nejm.org at UC SHARED JOURNAL COLLECTION on October 14, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved. case records of the massachusetts gener al hospital n engl j med 363;16 nejm.org october 14, 2010 1561 adenopathy was present. The remainder of the examination was normal. Laboratory-test results are shown in Table 1. Morphine sulfate and an- other dose of ampicillin–sulbactam were admin- istered intravenously, and ondansetron and oxy- codone were given orally. Approximately 2 hours after presentation, the patient was discharged and driven to this hospital for further evaluation. The patient was otherwise well. She had had a cesarean section 6 months earlier and lived with her partner and child, both of whom were healthy; she was monogamous with her partner. She drank alcohol socially, had smoked 10 ciga- rettes per day for 8 years, and did not use illicit drugs. She was taking no other medications and had no allergies. She owned cats, a dog, turtles, and a frog. She lived in a rural area of coastal southeastern Massachusetts. Her only foreign travel had been to the Caribbean years earlier. She had been to southern California a year ago. She was not aware of having received any tick bites. On examination, she appeared anxious and uncomfortable. The temperature was 37.1°C, the blood pressure 117/61 mm Hg, the pulse 102 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100% while she was breathing ambient air. The right hand, wrist, and axilla were tender, and the hand was swollen. A puncture wound was visible on the right thenar eminence, with surrounding erythema and red linear tracking on the ventral aspect of the wrist. There was right axillary lymphadenopathy. Sensation and peripheral puls- Table 1. Hematologic and Serum Chemical Laboratory Data. Variable Reference Range, Adults* 1st Admission to Other Hospital 1st Admission to This Hospital 2nd Admission to This Hospital Hematocrit (%) 36.0–46.0 (women) 39 34.0 33.1 Hemoglobin (g/dl) 12.0–16.0 (women) 13.8 12.4 12.3 White-cell count (per mm3) 4500–11,000 8700 7900 6300 Differential count (%) Neutrophils 40–70 75 75 80 Lymphocytes 22–44 19 19 14 Monocytes 4–11 5 5 6 Eosinophils 0–8 1 1 0 Basophils 0–3 1 0 0 Platelet count (per mm3) 150,000–400,000 201,000 170,000 144,000 Sodium (mmol/liter) 135–145 135 135 Potassium (mmol/liter) 3.4–4.8 3.1 3.3 Chloride (mmol/liter) 100–108 103 103 Carbon dioxide (mmol/liter) 23.0–31.9 22.8 23.7 Protein (g/dl) Total 6.0–8.3 5.8 Albumin 3.3–5.0 3.4 Globulin 2.6–4.1 2.4 Alkaline phosphatase (U/liter) 30–100 124 Aspartate aminotransferase (U/liter) 9–32 181 Alanine aminotransferase (U/liter) 7–30 174 Heterophile antibody Negative Negative * Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical condi- tions that could affect the results. They may therefore not be appropriate for all patients. The New England Journal of Medicine Downloaded from www.nejm.org at UC SHARED JOURNAL COLLECTION on October 14, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved. T h e n e w e ngl a nd j o u r na l o f m e dic i n e n engl j med 363;16 nejm.org october 14, 20101562 es were normal, and there was no fluctuance that was suggestive of an abscess. The remain- der of the examination was normal. A radio- graph of the hand showed normal joint spaces and no foreign body. The level of glucose and tests of renal function were normal; other labo- ratory-test results are shown in Table 1. The patient was admitted to the observation unit. Morphine sulfate, ketorolac tromethamine, and ampicillin–sulbactam (third dose) were adminis- tered intravenously; acetaminophen was admin- istered orally; and the hand was elevated. Pain in the hand decreased, and 12 hours after arrival, the patient was discharged with instructions to take amoxicillin–clavulanic acid twice daily for 10 days, to elevate her right hand at all times, and to seek medical follow-up in 3 days, or sooner if the condition worsened. That evening, 6.5 hours after discharge from this hospital, the patient returned to the first hospital because of shaking chills, a tempera- ture of 40°C, headache, and generalized aching and arthralgias. On examination, the temperature was reportedly 38.5°C. Additional ampicillin– sulbactam, morphine, hydromorphone, diphen- hydramine, and ondansetron were administered, and a splint was applied. In the morning, she was transferred by ambulance to this hospital, arriving 31 hours after her initial presentation at this hospital. She reported that the pain in the hand and wrist had improved; pain in the right arm, axilla, and neck had increased; and head- ache, diffuse body aches, mild abdominal and low pelvic pain, and transient numbness and tingling in the back and legs had developed. She reported no urinary symptoms. The temperature was 39.0°C; other vital signs were stable. Erythema was decreased, cervical and axillary lymph nodes and the right hand were enlarged and tender, and the right hand Table 2. Results of Serologic Tests. Test Reference Range 2nd Admission to This Hospital Antibody to human immunodeficiency virus Nonreactive Nonreactive Bartonella antibody Bartonella henselae IgG Negative at <1:64 dilution Negative B. henselae IgM Negative at <1:20 dilution Negative B. quintana IgG Negative at <1:64 dilution Negative B. quintana IgM Negative at <1:20 dilution Negative Leptospirosis antibody Leptospira IgM Negative Negative Microagglutination Negative (out of 20 serovars) Negative (0 of 20 reacting) Lyme antibody Negative Negative Toxoplasma IgM Negative Negative IgG Negative Negative Rapid plasma reagin Nonreactive Nonreactive Francisella tularensis antibody Negative at <1:20 dilution, equivo- cal at 1:20 to 1:80, positive at 1:160 Negative at <1:20 dilution F. tularensis microagglutination Positive at 1:128 dilution Presumed negative at 1:4 dilution Ehrlichia chaffeensis IgM Negative at <1:20 dilution Negative at <1:20 dilution IgG Negative at <1:64 dilution Negative at <1:64 dilution Anaplasma phagocytophilum IgM Negative at <1:20 dilution Negative at <1:20 dilution IgG Negative at <1:64 dilution Negative at <1:64 dilution The New England Journal of Medicine Downloaded from www.nejm.org at UC SHARED JOURNAL COLLECTION on October 14, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved. case records of the massachusetts gener al hospital n engl j med 363;16 nejm.org october 14, 2010 1563 was edematous (2+), with decreased range of motion of the wrist and fingers. Levels of glu- cose and bilirubin were normal, as were the erythrocyte sedimentation rate and the results of renal-function tests. Urinalysis revealed 1+ ke- tones and trace urobilinogen and was otherwise normal. Tests for antibodies to hepatitis A and C viruses were negative; other test results are shown in Tables 1 and 2. Examination of Wright-stained smears of whole blood (thick and thin preparations) showed no evidence of intra- cellular or extracellular organisms or morulae. Chest radiographs showed minimal patchy air- space opacities in the middle lobe of the right lung, without focal consolidation, and abdomi- nal ultrasonography was normal. Specimens of blood were cultured. Vancomycin, levofloxacin, morphine sulfate, ketorolac tromethamine, and normal saline were administered intravenously. Infectious-disease specialists were consulted, and the administration of ampicillin–sulbactam and azithromycin was begun. Her symptoms improved. On the second hospital day, the administra- tion of azithromycin was stopped, and doxycy- cline was begun. The swelling, pain, and ery- thema markedly diminished, and the temperature was normal. On the fourth day, the patient was discharged with instructions to take amoxicil- lin–clavulanic acid, doxycycline, and levofloxa- cin for 2 weeks. At follow-up 7 weeks later, she felt well, and the physical examination was normal. A diag- nostic test was performed. Differ en ti a l Di agnosis Dr. Arnold N. Weinberg: I am aware of the diagnosis. The headline introducing this case could read, “Sick Cat Bites Healthy Veterinary Aid in South- eastern Massachusetts.” After a fling in the rural outdoors, a domestic cat had returned home ill with fever, jaundice, and anemia. A healthy young woman in contact with multiple healthy pets at home and a variety of animals at work was bitten by the cat. Several days later, an acute, painful cellulitis developed on the thenar area of the patient’s hand at the site of the initial puncture wound. Although no fever was present, she was treated with ampicillin–sulbactam and amoxicillin–clav- ulanic acid. In response to the medication, the local cellulitis and pain were substantially di- minished, without evidence of local complica- tions, but nevertheless, chills and high fevers, pain in the whole arm and axillary nodes, head- ache, and generalized constitutional symptoms developed. In reviewing this case, I have concluded that the patient most likely had a dual infection caused by the cat bite. After a puncture wound, an acute cellulitis developed that responded to broad-spectrum penicillins. This was followed by a subacute infection that was successfully treated with a combination of levofloxacin and doxycycline. Cellulitis The initial acute painful cellulitis could have been polymicrobial and caused by organisms re- siding on the patient’s skin or in the cat’s mouth (Tables 3 and 4). The normal flora of the oral cavity of the domestic cat includes Pasteurella mul- tocida and other bacteria, as well as pathogens that may be acquired from the environment or from mammals and birds that the cat may have come in contact with (Table 4).1 Although the initial process in this case is consistent with a streptococcal cellulitis, I would have expected a more acute onset, more fever, and a rapid resolution with penicillin therapy. Blood cultures were not available, and the initial cellulitis exudate was not sampled. The logical choice for the initial process remains P. multocida. This organism resides in the anterior oral cavity Table 3. Bacterial Flora Commonly Associated with Humans. Normal Staphylococcal species Streptococcal species Corynebacteria and diphtheroids Anaerobes Transient, from oral and respiratory sources Staphylococci, including Staphylococcus aureus Streptococci, including Streptococcus pyogenes and S. milleri Anaerobes Transient, from pets and veterinary clinic Pasteurella species (especially Pasteurella multocida) Bartonella species (especially Bartonella henselae) Moraxella species Staphylococcal and streptococcal species Salmonella species The New England Journal of Medicine Downloaded from www.nejm.org at UC SHARED JOURNAL COLLECTION on October 14, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved. T h e n e w e ngl a nd j o u r na l o f m e dic i n e n engl j med 363;16 nejm.org october 14, 20101564 of the cat and is the most frequent cause of in- fection, including painful cellulitis, from cat bites. For this reason, the routine protocol after a cat bite in veterinary practices consists of, at mini- mum, a single dose of amoxicillin. The powerful jaws and sharp incisor teeth of the cat can eas- ily pierce the skin and inject organisms into soft tissues, tendon sheaths, joint spaces, or even subperiosteal bone. None of these complications ensued. On clinical and statistical grounds, the pathogen P. multocida is the most likely cause of the initial mild fever and subsequent severe local pain and swelling that were consistent with cel- lulitis, without changed progression of the local puncture wound.2,3 Systemic infection I assume that the cat was healthy, active, and curious when it wandered from home. During this period of freedom, it probably drank water wherever available, chased birds and small mam- mals (some of which were perhaps slowed by ill- ness), and ingested tissue from a fresh kill or carcass. The list of potential pathogens acquired during this outdoor adventure includes several that could have resulted in the cat’s acute illness and the patient’s subacute illnesses that devel- oped while she was on broad-spectrum penicil- lins (Table 4).1,4 The differential diagnosis should include pathogens from the environment and from liv- ing or dead mammals or birds. The cat could have become exposed to leptospira species by ingesting contaminated water. The acute illness in the cat is consistent with this diagnosis, but a cat bite is not a characteristic mode of trans- mission to humans, and the illness is not typi- cally subacute. The same argument can be made for Listeria monocytogenes, which almost always follows ingestion and occasionally the inhala- tion of organisms and does not characteristi- cally cause cellulitis or lymphadenitis, especially in immunocompetent hosts. Nocardia species, which contaminate soil, can cause a local cellu- litis, often with nodular lymphangitis. The clini- cal characteristics of the cellulitis and the sub- acute systemic illness make this an unlikely diagnosis. Among pathogens that are associated with mammals and birds, Erysipelothrix rhusio- pathiae, the cause of erysipeloid, and Streptobacil- lus moniliformis, the agent of rat-bite fever, should be mentioned. On rare occasions, these organ- isms have been associated with illness in cats, and they could be transmitted from the wild to a patient by a bite. However, erysipeloid is char- acterized by a superficial cellulitis with central clearing, and rat-bite fever by a generalized macu- lar and papular rash. The cat’s acute illness and transmission of the causative agent to the patient through a bite is most compatible, in this geographic region, with Francisella tularensis. The patient’s subacute illness, with high fever, headache, painful re- gional lymphadenopathy, generalized arthralgias, and mild liver-function abnormalities, is charac- teristic of infection with F. tularensis, as was the response to treatment with levofloxacin and doxycycline. This highly successful pathogen can persist for months in nature in mud, water, and mammal or bird carcasses. It can be spread to humans by ingestion, inhalation, tick and deer- f ly bites, contact with infected tissues, or an animal bite. In the United States between 2000 and 2008, an average of 125 cases per year was reported to the Centers for Disease Control and Prevention (CDC); the highest prevalence was in Missouri, Arkansas, Oklahoma, and Massachu- setts (www.cdc.gov/tularemia). Of the average of 10 cases per year in Massachusetts, the majority Table 4. Oral and Acquired Flora That May Be Associated with Cats.* Normal oral cavity Pasteurella multocida Bartonella henselae Moraxella species Staphylococci and streptococci Anaerobes Acquired from soil and water environment Leptospira species Listeria species Nocardia species Francisella tularensis Mammals and birds Streptobacillus moniliformis Erysipelothrix rhusiopathiae Coxiella burnetii F. tularensis * These flora may cause disease in a cat or be transiently carried orally or on claws.1 The New England Journal of Medicine Downloaded from www.nejm.org at UC SHARED JOURNAL COLLECTION on October 14, 2010. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved. case records of the massachusetts gener al hospital n engl j med 363;16 nejm.org october 14, 2010 1565 have occurred in southeastern coastal regions, particularly on the island of Martha’s Vineyard.5 Approximately 75% of cases of tularemia in the United States are manifested by a tender region- al lymph node and a local papule that evolves to a chancriform lesion; such cases are referred to as ulceroglandular