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Prevention of infections caused by Haemophilus influenzae
51
Infectious Diseases Newsletter 7(7) July 1988
Prevention of Infections Caused by
Haemophilus Influenzae Sheldon Kaplan Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
Haemophilus influenzae type b (Hib) is the leading cause of bacterial meningitis in children in the United States. Epiglottitis, uvulitis, bacteremia, septic arthritis, osteomyelitis, cellulitis, and pneumonia may also be caused by Hib. Children with underlying deficiencies in host defenses, including children with anatomic or functional asplenia, are at increased risk for infections caused by H. influenzae. Nontypable H. influenzae are associated with upper respiratory infections such as otitis media and sinusitis, and are frequently implicated in cases of bronchitis in adults. The prevention of systemic infections caused by Hib includes both immunization of children/> 18 months, and chemoprophylaxis in specific circumstances. Although several reports have documented the spread of H. influenzae within families and among children in chronic care facilities, the risk of acquiring secondary haemophilus disease has not been determined. The Centers for Disease Control (CDC) organized an investigation of 1147 households in which a case of meningitis caused by Hib had occurred; eight households (0.07%) had nine associated cases of invasive infection from Hib within 30 days after the onset of meningitis in the index case. Household contacts, i.e., persons who actually resided in the same house as the index case, had an attack rate of 0.21%, a risk 585 times that for the age-adjusted risk in the general population. As expected, the greatest risk for secondary disease (6.0%) occurred in household contacts less than one year of age [95% confidence limits (CL): 1.3 = 16.6%]. The risk for all children under 48 months was 2.1% (95% CL 0.9 = 4.2%). The risk for
household contacts over 4 years of age was negligible. A smaller CDC study determined that the secondary attack rate for household contacts less than 2 years of age was 4.9% (95% CL 1.4 = 12.2%). Subsequent reports have documented that, although a rare occurrence, adults exposed to children with either infection or nasopharyngeal carriage of Hib may become ill themselves, especially with epiglottitis. This is an important point because it is possible that adult contacts of a child infected with Hib who are at increased risk of a secondary infection may not be limited to household contacts or other adults in contact with the patient for 4 or more hours per day. While there is no argument that an increased risk of secondary infection with Hib exists for household contacts, there are conflicting data regarding the risk of secondary disease in child care settings. It does appear that the nasopharyngeal colonization rate (35%) of children in child care settings in which more than one child has developed systemic disease caused by Hib is greater than that observed when only one case occurred (15%). However, there is a wide variation in rates of colonization, and the rates are generally higher in children less than 24 months of age. According to two studies, there is an increased risk of secondary disease caused by Hib in children attending child care facilities. 1) For all child care center contacts of a primary case, the risk of a secondary associated case within 60 days was 0.17% (12/7027; 95% CL 0.07-0.27%) in Seattle-King County, Washington; Atlanta, Georgia; and the State of Oklahoma. 2) In a second subsequent study from © 1988 Elsevier Science Publishing Co., Inc. 0278-2316/88/$0.00 + 2.20
Oklahoma, 7/1253 (0.6%) contacts developed secondary disease within 60 days of the primary case. The risk for secondary disease was greater for children under two years in both studies. However, in two other studies in Minnesota and in Dallas, Texas, the rates of secondary disease in child care settings were significantly lower than those reported for household contacts. The different conclusions reached in these prospective studies are important because the risk of secondary disease in child care settings determines the need for prophylaxis. Unfortunately, there has been no satisfactory explanation for why these studies yielded such different conclusions. Perhaps geographic, socioeconomic, or genetic differences contributed, in part, to the differences in the findings. Of currently available, perorally administrable antimicrobics, only rifampin reliably eradicates nasopharyngeal colonization (in approximately 90% of carders). Other agents, such as anlpicillin, cefaclor, trimethoprimsulfamethoxazole, and erythromycinsulfasoxazole, have not proven to be effective. When rifampin is administered as a single daily dose of 20 mg/kg (not to exceed 600 mg) to household contacts of a child with systemic infection caused by Hib, the risk of secondary cases in young children is reduced substantially. Unfortunately, the only large study to examine the efficacy of rifampin in the prevention of secondary infections from Hib was imperfect, and it is unlikely that a second evaluation will be made. Nevertheless, chemoprophylaxis with rifampin is recommended for all adult and child household contacts of children with systemic disease
52 Infectious Diseases Newsletter 7(7) July 1988
caused by Hib if another child less than 4 years of age resides in the home. Moreover, rifampin should be given to the index patient as well as contacts who have been immunized with the vaccine for Hib. Several cases of secondary infection with Hib have been reported despite proper administration of rifampin to household contacts. Possibly, some family members or friends who were nasopharyngeal carriers of Hib were not considered household contacts (e.g., grandparents, an uncle, or a neighbor). Hib resistant to rifampin have rarely been responsible for a secondary infection. Certainly, rifampin does not eliminate Hib from all cartiers. Finally, a new strain of Hib may colonize after administration of rifampin was terminated. Thus, even though the recommended chemoprophylaxis with rifampin was correctly followed, the involved family should be warned that anyone who becomes ill or develops fever should seek medical attention promptly. The most controversial aspect of chemoprophylaxis with rifampin relates to child care center contacts exposed to a single case of invasive disease caused by Hib. The study organized by the CDC not only found an increased risk of secondary infection with Hib in child care facility contacts of a primary case, but also that rifampin effectively prevented secondary cases: secondary infections in 10/755 child care center contacts who did not take rifampin versus 0/570 contacts who did take rifampin. In individual child care facilities, where only one child developed infection with Hib, 47 of 119 centers achieved/>75% compliance in administration of rifampin in the classroom at risk versus 0 of 10 centers where a secondary case developed (p < 0.02). Rifampin was also found to significantly lower the risk of subsequent cases in the second study in Oklahoma. The recommendations of the Immunizations Practices Advisory Committee (ACIP) of the CDC with regard
to chemoprophylaxis with rifampin in child care classrooms in which a case of disease caused by Hib has occurred are as follows: "In a day-care classroom in which a case of systemic Hib disease has occurred, and in which one or more children under two years old have been exposed, strong consideration should be given to administering rifampin prophylaxis to all children and staff in the classroom, regardless of age." The Committee on Infectious Diseases of the American Academy of Pediatrics states: "Although the advisability of rifampin prophylaxis in day care groups in which a single case has occurred is controversial, most experts advise administering rifampin to "all infants and supervisory personnel when two or more cases of invasive disease have occurred among attendees within 61) days." Thus, two conflicting recommendations exist for the prophylactic use of rifampin in child care classroom contacts of a child with invasive infection caused by Hib. The difficulties in organizing the private or clinic physicians of child care contacts to prescribe rifampin for prophylaxis requires the input of the local public health officials. Furthermore, to insure that the children are compliant in taking the rifampin, some authorities recommend that the rifampin be administered in the child care center under close supervision. It is estimated that over 75% of the classroom contacts need to receive rifampin in order to avoid secondary cases. Ideally, for this strategy to be implemented effectively, the public health officials would provide the rifampin as well as supervise its administration. It is unlikely that unified recommendations will be forthcoming from the ACIP and AAP until a better estimate of the risk of secondary cases in child care facilities is available. Until such time, each physician must decide how to proceed on a case-bybase basis. For example, in child care homes, the number of children © 1988 Elsevier Science Publishing Co., Inc. 0278-2316/8S/$0.00 + 2.20
being cared for is limited and the ,~tensity of exposure is much akin to household exposure; hence, chemoprophylaxis with rifampin seems quite reasonable. Children with functional or anatomic asplenia are at increased risk lbr developing overwhelming infections caused by Hib (as well as by pneumococci). Chemoprophylaxis with penicillin was efficacious in preventing pneumococcal infections in children with sickle celt anemia. Although not studied, amoxicillin (20 mg/kg per day) would seem reasonable for these children who are 3 years of age or less. However, infections caused by Hib resistant to ampicillin (beta-lactamase producers) would not be prevented, and might possibly be promoted. Currently, a conjugate vaccine. consisting of the capsular polysaccharide of Hib coupled to diphtherial toxoid, is recommended for all children at 18 months of age. If conjugate vaccines are found to be efficacious for preventing systemic infections with Hib in children as young as 2 months of age, the controversies regarding chemoprophylaxis with rifampin would be of historical interest. Non-typable H. influenzae are the second most common pathogens isolated from the middle ears of children with acute otitis media. Children less than 2 years of age who have had three or more episodes of acute otitis media of a 6-month period, but without persistent effusion, may benefit from the prophylactic administration of amoxicillin or sulfisoxazole (20 mg/kg each night). Controlled trials have shown that prophylaxis may decrease the episodes of acute otitis media by 47-90% in such children. No other means of preventing infections caused by non-typable H. influenzae are presently available.
Bibliography Band JD, Fraser DW, Ajello G: Prevention of Haemophilus influenzae type b disease. JAMA 251:2381-2386, 1984.
53 Infectious Diseases Newsletter 7(7) July 1988 Fleming DW, Leibenhaut MH, Albanes D, et al: Secondary Haemphilus influenzae type b in day-care facilities. Risk factors and prevention. JAMA 254:509-514, 1985. Granoff DM, Daum RS: Spread of Haemophilus influenzae type b; recent epidemiologic and therapeutic considerations, J Pediatr 97:854-860, 1980. Makintubee S, Istre GR, Ward Jl: Transmission of invasive Haemophilus in-
fluenzae type b disease in day care settings. J Pediatr 111:180-186, 1987. Murphy TV, Clements JF, Breedlove JA, et al: Risk of subsequent disease among day-care contacts of patients with systemic Haemophilus influenze type b disease. N Engl J Med 316:5-10, 1987. Osterholm MT, Pierson LM, White KE, et al: The risk of subsequent transmission of Haemophilus influenzae type b disease among children in day care.
Results of a two-year statewide prospective surveillance and contact survey. N Engl J Med 316:1-5, 1987. Report of the Committee on Infectious Disease, 12th ed. American Academy of Pediatrics, Elk Grove Village, IL, 1986. Ward JI, Fraser DW, Baraff LJ, Plikaytis BD: Haemophilus influenzae meningitis. A national study of secondary spread in household contacts. N Engl J Med 301:122-126, 1979.
CASE REPORT A twenty-five-year-old white female, a receipient of a cadaveric renal transplant in 1969, maintained the allograft while receiving azathioprine and prednisone. However, in 1986, hospital admission was necessitated by the persistence of a sore throat with fever of 40°C, fatigue, and cervical adenitis for 2 weeks; her peripheral leukocyte count was 2,900/txl. Pain referred to her left pharynx increased despite administration of penicillin (IM injection, 1 week before admission) and cefaclor (PO, 3 days before admission). On physical examination she was well developed, alert, and complained of pain in the left tonsillar area. The left tonsil was swollen and there was an ulcer with greyish necrotic borders at the superior pole. No other oropharyngeal lesions or masses were observed. Tender nodes were palpable in the left submandibular area, and in the anterior and posterior cervical chains. Her neck was supple. On admission, there were 2,700 leukocytes/p,l in her peripheral blood with 54% polymorphonuclear and 16% band neutrophils, 19% lymphocytes, 11% monocytes; the platelets appeared to be decreased. The morphology of the lymphocytes was normal; no Downey cells were found. The blood urea nitrogen was 18 mg/dl (normal: 8-25) and the plasma creatinine was 1.1 mg/dl (normal: 0.6-1.5). Cultures of the blood and urine gave no growth. A
Gram stained smear from a left tonsillar biopsy revealed a few leukocytes, rare Gram-positive cocci in pairs and chains, and rare Gram-negative bacilli. Aerobic cultures of the tonsillar tissue yielded alpha-hemolytic streptococci, while there was no growth in anaerobic cultures. A Monospot test was positive and the titer of VCA-IgM for Epstein Barr virus was 1:20; cultures for herpes simplex viruses were negative. The chest roentgenogram was unremarkable. A presumptive diagnosis of infectious mononucleosis with peritonsillar abscess was made. Treatment was begun with penicillin G (1 million units, IV, every 4 hours). The ulcer enlarged over the next 4 days and the tonsil was resected without complication. No pus was found and the surgical wound healed quickly. On the second postoperative day, the patient developed a fever of 41°C and had increasingly tender submandibular adenopathy. Several blood cultures yielded no growth. The patient was given clindamycin and acyclovir. On the sixth post-operative day, growth in cultures of the core of the resected left tonsil was identified as Bacteroides spp, Fusobacterium spp, and Capnocytophaga ochracea. Treatment with azathioprine, acyclovir, and clindamycin was discontinued and treatment with penicillin was continued for a total of 10 days. The patient improved steadily. She was discharged © 1988 Elsevier Science Publishing Co., Inc. 0278-2316/88/$0.00 + 2.20
on the fourteenth hospital day because she was afebrile and both the pharyngitis and leukopenia had resolved. Comment The genus Capnocytophaga was established in 1979 to incorporate the organisms formerly classified as Bacteriodes ochraceus and the Centers for Disease Control biogroup "Dysgonic Fermenter 1" (DF-1). There are two species in addition to C. ochraceus: C. sputigena and C. gingivalis. Characterized as fastidious, fusiform, capnophilic, non-spore forming Gram-negative bacilli, these nonflagellated facultative anaerobes are also noted for their unusual gliding motility on solid medium containing 2% agar. Biochemically, Capnocytophaga spp are oxidase-, catalase-, and indole-negative, as well as dysgonic fermenters of glucose, lactose, mannose, and sucrose (yielding succinate and acetate as metabolic end products). They cannot ferment mannitol, ribose, sorbitol, or xylose. Flat colonies with finger-like projections are characteristic of Capnocytophaga spp; they appear after 48-72 hours of incubation in 5-10% carbon dioxide, or in anaerobiosis. Unable to grow on MacConkey agar, they are notable for production of a yellow (ocher) pigment on blood agar. Isolation from clinical specimens is frequently made difficult by overgrowth of more rapidly growing bacteria. A recently developed selec-
Infectious Diseases Newsletter 7(7) July 1988
Prevention of Infections Caused by
Haemophilus Influenzae Sheldon Kaplan Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
Haemophilus influenzae type b (Hib) is the leading cause of bacterial meningitis in children in the United States. Epiglottitis, uvulitis, bacteremia, septic arthritis, osteomyelitis, cellulitis, and pneumonia may also be caused by Hib. Children with underlying deficiencies in host defenses, including children with anatomic or functional asplenia, are at increased risk for infections caused by H. influenzae. Nontypable H. influenzae are associated with upper respiratory infections such as otitis media and sinusitis, and are frequently implicated in cases of bronchitis in adults. The prevention of systemic infections caused by Hib includes both immunization of children/> 18 months, and chemoprophylaxis in specific circumstances. Although several reports have documented the spread of H. influenzae within families and among children in chronic care facilities, the risk of acquiring secondary haemophilus disease has not been determined. The Centers for Disease Control (CDC) organized an investigation of 1147 households in which a case of meningitis caused by Hib had occurred; eight households (0.07%) had nine associated cases of invasive infection from Hib within 30 days after the onset of meningitis in the index case. Household contacts, i.e., persons who actually resided in the same house as the index case, had an attack rate of 0.21%, a risk 585 times that for the age-adjusted risk in the general population. As expected, the greatest risk for secondary disease (6.0%) occurred in household contacts less than one year of age [95% confidence limits (CL): 1.3 = 16.6%]. The risk for all children under 48 months was 2.1% (95% CL 0.9 = 4.2%). The risk for
household contacts over 4 years of age was negligible. A smaller CDC study determined that the secondary attack rate for household contacts less than 2 years of age was 4.9% (95% CL 1.4 = 12.2%). Subsequent reports have documented that, although a rare occurrence, adults exposed to children with either infection or nasopharyngeal carriage of Hib may become ill themselves, especially with epiglottitis. This is an important point because it is possible that adult contacts of a child infected with Hib who are at increased risk of a secondary infection may not be limited to household contacts or other adults in contact with the patient for 4 or more hours per day. While there is no argument that an increased risk of secondary infection with Hib exists for household contacts, there are conflicting data regarding the risk of secondary disease in child care settings. It does appear that the nasopharyngeal colonization rate (35%) of children in child care settings in which more than one child has developed systemic disease caused by Hib is greater than that observed when only one case occurred (15%). However, there is a wide variation in rates of colonization, and the rates are generally higher in children less than 24 months of age. According to two studies, there is an increased risk of secondary disease caused by Hib in children attending child care facilities. 1) For all child care center contacts of a primary case, the risk of a secondary associated case within 60 days was 0.17% (12/7027; 95% CL 0.07-0.27%) in Seattle-King County, Washington; Atlanta, Georgia; and the State of Oklahoma. 2) In a second subsequent study from © 1988 Elsevier Science Publishing Co., Inc. 0278-2316/88/$0.00 + 2.20
Oklahoma, 7/1253 (0.6%) contacts developed secondary disease within 60 days of the primary case. The risk for secondary disease was greater for children under two years in both studies. However, in two other studies in Minnesota and in Dallas, Texas, the rates of secondary disease in child care settings were significantly lower than those reported for household contacts. The different conclusions reached in these prospective studies are important because the risk of secondary disease in child care settings determines the need for prophylaxis. Unfortunately, there has been no satisfactory explanation for why these studies yielded such different conclusions. Perhaps geographic, socioeconomic, or genetic differences contributed, in part, to the differences in the findings. Of currently available, perorally administrable antimicrobics, only rifampin reliably eradicates nasopharyngeal colonization (in approximately 90% of carders). Other agents, such as anlpicillin, cefaclor, trimethoprimsulfamethoxazole, and erythromycinsulfasoxazole, have not proven to be effective. When rifampin is administered as a single daily dose of 20 mg/kg (not to exceed 600 mg) to household contacts of a child with systemic infection caused by Hib, the risk of secondary cases in young children is reduced substantially. Unfortunately, the only large study to examine the efficacy of rifampin in the prevention of secondary infections from Hib was imperfect, and it is unlikely that a second evaluation will be made. Nevertheless, chemoprophylaxis with rifampin is recommended for all adult and child household contacts of children with systemic disease
52 Infectious Diseases Newsletter 7(7) July 1988
caused by Hib if another child less than 4 years of age resides in the home. Moreover, rifampin should be given to the index patient as well as contacts who have been immunized with the vaccine for Hib. Several cases of secondary infection with Hib have been reported despite proper administration of rifampin to household contacts. Possibly, some family members or friends who were nasopharyngeal carriers of Hib were not considered household contacts (e.g., grandparents, an uncle, or a neighbor). Hib resistant to rifampin have rarely been responsible for a secondary infection. Certainly, rifampin does not eliminate Hib from all cartiers. Finally, a new strain of Hib may colonize after administration of rifampin was terminated. Thus, even though the recommended chemoprophylaxis with rifampin was correctly followed, the involved family should be warned that anyone who becomes ill or develops fever should seek medical attention promptly. The most controversial aspect of chemoprophylaxis with rifampin relates to child care center contacts exposed to a single case of invasive disease caused by Hib. The study organized by the CDC not only found an increased risk of secondary infection with Hib in child care facility contacts of a primary case, but also that rifampin effectively prevented secondary cases: secondary infections in 10/755 child care center contacts who did not take rifampin versus 0/570 contacts who did take rifampin. In individual child care facilities, where only one child developed infection with Hib, 47 of 119 centers achieved/>75% compliance in administration of rifampin in the classroom at risk versus 0 of 10 centers where a secondary case developed (p < 0.02). Rifampin was also found to significantly lower the risk of subsequent cases in the second study in Oklahoma. The recommendations of the Immunizations Practices Advisory Committee (ACIP) of the CDC with regard
to chemoprophylaxis with rifampin in child care classrooms in which a case of disease caused by Hib has occurred are as follows: "In a day-care classroom in which a case of systemic Hib disease has occurred, and in which one or more children under two years old have been exposed, strong consideration should be given to administering rifampin prophylaxis to all children and staff in the classroom, regardless of age." The Committee on Infectious Diseases of the American Academy of Pediatrics states: "Although the advisability of rifampin prophylaxis in day care groups in which a single case has occurred is controversial, most experts advise administering rifampin to "all infants and supervisory personnel when two or more cases of invasive disease have occurred among attendees within 61) days." Thus, two conflicting recommendations exist for the prophylactic use of rifampin in child care classroom contacts of a child with invasive infection caused by Hib. The difficulties in organizing the private or clinic physicians of child care contacts to prescribe rifampin for prophylaxis requires the input of the local public health officials. Furthermore, to insure that the children are compliant in taking the rifampin, some authorities recommend that the rifampin be administered in the child care center under close supervision. It is estimated that over 75% of the classroom contacts need to receive rifampin in order to avoid secondary cases. Ideally, for this strategy to be implemented effectively, the public health officials would provide the rifampin as well as supervise its administration. It is unlikely that unified recommendations will be forthcoming from the ACIP and AAP until a better estimate of the risk of secondary cases in child care facilities is available. Until such time, each physician must decide how to proceed on a case-bybase basis. For example, in child care homes, the number of children © 1988 Elsevier Science Publishing Co., Inc. 0278-2316/8S/$0.00 + 2.20
being cared for is limited and the ,~tensity of exposure is much akin to household exposure; hence, chemoprophylaxis with rifampin seems quite reasonable. Children with functional or anatomic asplenia are at increased risk lbr developing overwhelming infections caused by Hib (as well as by pneumococci). Chemoprophylaxis with penicillin was efficacious in preventing pneumococcal infections in children with sickle celt anemia. Although not studied, amoxicillin (20 mg/kg per day) would seem reasonable for these children who are 3 years of age or less. However, infections caused by Hib resistant to ampicillin (beta-lactamase producers) would not be prevented, and might possibly be promoted. Currently, a conjugate vaccine. consisting of the capsular polysaccharide of Hib coupled to diphtherial toxoid, is recommended for all children at 18 months of age. If conjugate vaccines are found to be efficacious for preventing systemic infections with Hib in children as young as 2 months of age, the controversies regarding chemoprophylaxis with rifampin would be of historical interest. Non-typable H. influenzae are the second most common pathogens isolated from the middle ears of children with acute otitis media. Children less than 2 years of age who have had three or more episodes of acute otitis media of a 6-month period, but without persistent effusion, may benefit from the prophylactic administration of amoxicillin or sulfisoxazole (20 mg/kg each night). Controlled trials have shown that prophylaxis may decrease the episodes of acute otitis media by 47-90% in such children. No other means of preventing infections caused by non-typable H. influenzae are presently available.
Bibliography Band JD, Fraser DW, Ajello G: Prevention of Haemophilus influenzae type b disease. JAMA 251:2381-2386, 1984.
53 Infectious Diseases Newsletter 7(7) July 1988 Fleming DW, Leibenhaut MH, Albanes D, et al: Secondary Haemphilus influenzae type b in day-care facilities. Risk factors and prevention. JAMA 254:509-514, 1985. Granoff DM, Daum RS: Spread of Haemophilus influenzae type b; recent epidemiologic and therapeutic considerations, J Pediatr 97:854-860, 1980. Makintubee S, Istre GR, Ward Jl: Transmission of invasive Haemophilus in-
fluenzae type b disease in day care settings. J Pediatr 111:180-186, 1987. Murphy TV, Clements JF, Breedlove JA, et al: Risk of subsequent disease among day-care contacts of patients with systemic Haemophilus influenze type b disease. N Engl J Med 316:5-10, 1987. Osterholm MT, Pierson LM, White KE, et al: The risk of subsequent transmission of Haemophilus influenzae type b disease among children in day care.
Results of a two-year statewide prospective surveillance and contact survey. N Engl J Med 316:1-5, 1987. Report of the Committee on Infectious Disease, 12th ed. American Academy of Pediatrics, Elk Grove Village, IL, 1986. Ward JI, Fraser DW, Baraff LJ, Plikaytis BD: Haemophilus influenzae meningitis. A national study of secondary spread in household contacts. N Engl J Med 301:122-126, 1979.
CASE REPORT A twenty-five-year-old white female, a receipient of a cadaveric renal transplant in 1969, maintained the allograft while receiving azathioprine and prednisone. However, in 1986, hospital admission was necessitated by the persistence of a sore throat with fever of 40°C, fatigue, and cervical adenitis for 2 weeks; her peripheral leukocyte count was 2,900/txl. Pain referred to her left pharynx increased despite administration of penicillin (IM injection, 1 week before admission) and cefaclor (PO, 3 days before admission). On physical examination she was well developed, alert, and complained of pain in the left tonsillar area. The left tonsil was swollen and there was an ulcer with greyish necrotic borders at the superior pole. No other oropharyngeal lesions or masses were observed. Tender nodes were palpable in the left submandibular area, and in the anterior and posterior cervical chains. Her neck was supple. On admission, there were 2,700 leukocytes/p,l in her peripheral blood with 54% polymorphonuclear and 16% band neutrophils, 19% lymphocytes, 11% monocytes; the platelets appeared to be decreased. The morphology of the lymphocytes was normal; no Downey cells were found. The blood urea nitrogen was 18 mg/dl (normal: 8-25) and the plasma creatinine was 1.1 mg/dl (normal: 0.6-1.5). Cultures of the blood and urine gave no growth. A
Gram stained smear from a left tonsillar biopsy revealed a few leukocytes, rare Gram-positive cocci in pairs and chains, and rare Gram-negative bacilli. Aerobic cultures of the tonsillar tissue yielded alpha-hemolytic streptococci, while there was no growth in anaerobic cultures. A Monospot test was positive and the titer of VCA-IgM for Epstein Barr virus was 1:20; cultures for herpes simplex viruses were negative. The chest roentgenogram was unremarkable. A presumptive diagnosis of infectious mononucleosis with peritonsillar abscess was made. Treatment was begun with penicillin G (1 million units, IV, every 4 hours). The ulcer enlarged over the next 4 days and the tonsil was resected without complication. No pus was found and the surgical wound healed quickly. On the second postoperative day, the patient developed a fever of 41°C and had increasingly tender submandibular adenopathy. Several blood cultures yielded no growth. The patient was given clindamycin and acyclovir. On the sixth post-operative day, growth in cultures of the core of the resected left tonsil was identified as Bacteroides spp, Fusobacterium spp, and Capnocytophaga ochracea. Treatment with azathioprine, acyclovir, and clindamycin was discontinued and treatment with penicillin was continued for a total of 10 days. The patient improved steadily. She was discharged © 1988 Elsevier Science Publishing Co., Inc. 0278-2316/88/$0.00 + 2.20
on the fourteenth hospital day because she was afebrile and both the pharyngitis and leukopenia had resolved. Comment The genus Capnocytophaga was established in 1979 to incorporate the organisms formerly classified as Bacteriodes ochraceus and the Centers for Disease Control biogroup "Dysgonic Fermenter 1" (DF-1). There are two species in addition to C. ochraceus: C. sputigena and C. gingivalis. Characterized as fastidious, fusiform, capnophilic, non-spore forming Gram-negative bacilli, these nonflagellated facultative anaerobes are also noted for their unusual gliding motility on solid medium containing 2% agar. Biochemically, Capnocytophaga spp are oxidase-, catalase-, and indole-negative, as well as dysgonic fermenters of glucose, lactose, mannose, and sucrose (yielding succinate and acetate as metabolic end products). They cannot ferment mannitol, ribose, sorbitol, or xylose. Flat colonies with finger-like projections are characteristic of Capnocytophaga spp; they appear after 48-72 hours of incubation in 5-10% carbon dioxide, or in anaerobiosis. Unable to grow on MacConkey agar, they are notable for production of a yellow (ocher) pigment on blood agar. Isolation from clinical specimens is frequently made difficult by overgrowth of more rapidly growing bacteria. A recently developed selec-