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Q fever in pregnancy
Journal of Infection (1997) 34, 75-78
CASE REPORT
Q Fever in Pregnancy H. Ludlam *~, T. G. W r e g h i t f , S. Thornton 2, B. J. Thomson 3, N. J. Bishop 4, S. Coomber 5 and J. Cunniffe ~ 1Clinical Microbiology and Public Health LaboratolN, 2University Department of Obstetrics and Gynaecology, 3Department of Medicine, 4University Department of Paediatrics, SDepartment of Occupational Health, Addenbrooke's NHS Trust, Cambridge CB2 20W, U.K. Accepted for publication 3 August 1996
We describe a case of acute symptomatic infection with Coxiella burnetii acquired between the 16th and 28th week of pregnancy. Oral ciprofloxacin therapy was started on diagnosis, at the 28th week of pregnanc!J, but symptoms were unabated after 3 weeks treatment, suggesting persisting infection of the products of conception. Caesarean section was therefore performed at 32 weeks gestation when a healthy infant was delivered, and subsequent investigations showed no evidence of transplacental spread of infection. Infection control measures were applied at the time of delivery to minimize the risk of infection to obstetricians and midwives from potentially infectious products of conception.
Introduction Coxiella burnetii is a well recognized cause of stillbirth and abortion in animals. H u m a n infection (0 fever) is usually acquired by inhalation of aerosols of excretions and secretions from infected animals, although ingestion of infected milk and tick bites are occasionally implicated. Exposure to parturient animals poses the greatest risk due to aerosolization of large numbers of organisms from infected amniotic fluid. H u m a n infection with C. burnetii in pregnancy has recently been linked to stillbirth and abortion. 1 The recent report of Q fever infection in an obstetrician delivering such a case 2 prompts us to report our own experience.
Case Report A 26-year-old pregnant nurse presented at 28 weeks gestation with a history of continuous malaise dating from the time of conception. She had also experienced four episodes of flu-like illness with sore throat, cough, fever, headaches and generalized musculoskeletal pains during this time. Physical examination was unremarkable and the chest X-ray was normal. There was no evidence of placental insufficiency and fetal development was normal. Haematological examination showed a slightly low haemoglobin (10.4 g/dl, normal non-pregnant range 11.5-16.5 g/dl) and a neutrophilia * Address correspondence to: H. Ludlam. 0163-4453/97/010075 +04 $12.00/0
10.4 X 109/1 (normal non-pregnant range 2.0-7.5 x 109/1). The serum C-Reactive protein (CRP) concentration was normal. Biochemical investigation showed hypoalbuminaemia (27.0g/1, normal non-pregnant range 3 0 . 0 - 5 1 . 0 g/l) and normal liver function tests apart from a raised bilirubin (28.0 ~tmol/1, normal non-pregnant range 2 . 0 - 1 7 . 0 gmol/l). Bacterial cultures from urine, blood and vagina did not reveal any pathogen. A diagnosis of acute Q fever was made on the basis of seroconversion to C. burnetii between the 16th and 2 8th week of pregnancy. The complement fixation test showed a rise in C. burnetii Phase 1 and 2 antibody titres from <8 to 64 and <8 to 256, respectively. The indirect immunofluorescence test (performed at Bristol Public Health Laboratory) showed a rise in C. burnetii IgG from <10 to > 1 2 8 0 and fgM from <10 to >1280. There was no serological evidence for recent infection with influenza A or B viruses, adenovirus, parvovirus, rubella virus, cytomegalovirus, chlamydia, Mycoplasma pneumoniae, Legionella pneumophila or Toxoplasma gondii. She gave a history of erythromycin allergy, confirmed by challenge which produced a generalized itchy rash. The patient refused to consider tetracycline therapy but agreed treatment with oral ciprofloxacin 5 0 0 m g bd. After 3 weeks ciprofloxacin therapy symptoms of malaise and generalized muscle pains continued unabated, suggesting persisting infection. The risk to mother and fetus of continuing the pregnancy was considered to be higher t h a n that of delivery and she was admitted for induction of labour at 32 weeks of pregnancy, local data showing © 1997 The British Society for the Study of Infection
76
H. Ludlam et aL
good neonatal outcome from this time onward. Induction of labour was unsuccessful and she proceeded to caesarean section 2 days later when a normal female infant weighing 1.88 kg was delivered. At the time of delivery, 2 h after the last dose of antibiotic, paired maternal serum and amniotic fluid ciprofloxacin levels were 0.9mg/1 and 0.5mg/1, respectively. The serum ciprofloxacin level in cord blood taken 3 h after the last maternal dose was 0.4 mg/1. In view of the maternal history and oxygen dependency the neonate received broad spectrum parental antibiotic therapy with penicillin, erythromycin and ciprofloxacin immediately after delivery. Haematological investigation was unremarkable, the ESR and CRP were normal and there were no biochemical abnormalities. The penicillin was stopped after 5 days when blood and surveillance cultures proved negative, but the erythromycin and ciprofloxacin were continued for a total of 2 weeks in view of the possibility of transplacental transmission of Q fever. However, serological investigation of the infant showed no evidence of fetal infection, cord blood taken at delivery being negative for C. burnetii IgM. Histological examination of placental sections revealed no abnormality with no evidence of past or current infection and immunocytochemical staining and culture of placenta were negative for C. burnetii. Following delivery, the mother's ciprofloxacin was discontinued and doxycycline 100 mg bd was prescribed for a further 2 weeks and symptoms slowly resolved thereafter. At review 4 weeks after delivery mother and baby were both well; 6 months after delivery, the mother's C. burnetii Phase 1 and 2 antibody titres had fallen fourfold compared with the titres at presentation.
Infection control and staff surveillance Non-essential staff were excluded from the delivery suite during labour. Although we attempted to exclude staff with conditions known to predispose to more serious infection (the pregnant, the immunocompromised or those with cardiovascular abnormalities) one obstetrician with a ventricular septal defect assisted at delivery. Staff present at delivery wore gloves and gowns as usual but in addition safety spectacles and 3M 8822 particulate respirator type face masks (Tower Supplies, Poole, Dorset) were worn. The possibility of aerosolization of Q fever organisms present in amniotic fluid was minimized by mopping the fluid as it emerged with swabs, careful handling of the placenta to avoid splashing and towelling the baby immediately after delivery. Clinical waste was disposed in accordance with local
guidelines for 'infection risk from blood', surfaces contaminated with amniotic fluid were disinfected with sodium hypochlorite. Delivery took place in the usual suites. No special arrangements were made other than allowing 3 h normal ventilation before re-use. No further infection control measures were applied to mother and baby following delivery. The 10 members of staff who were present during labour, and the husband who was also present, were offered, and accepted, prophylaxis with doxycycline 200 mg once daily for 7 days. All were asked to report any illness in the following 6 weeks. The member of staff with the ventricular septal defect received 1 months prophylaxis and was followed up for a total of 12 weeks. None reported any illness suggestive of Q fever. Serum samples were taken from the staff delivering the baby and placenta (three obstetricians, one midwife, one paediatrician and one obstetric theatre scrub nurse) at the time of delivery and 6 weeks later; none had antibodies to C. burnetii.
Discussion Raoult and Stein 2 in a review of the literature to 1994 recorded 15 published cases of Q fever in pregnancy. The outcome of pregnancy was normal in five cases, prematurity and low birth weight were noted in seven cases and fetal death in utero occurred in three cases. C. burnetii was isolated from six of 11 placentas. Infection in pregnancy may be primary or due to reactivation of a previous infection and the course may be acute or chronic. Infection of the products of conception is particularly liable to lead to chronic infeciton. 3 The serological response in our case indicated an acute infection acquired during pregnancy with no evidence for involvement of the products of conception. The prevalence of Q fever in our area is unknown but it is likely to be low as there is little local farming of livestock; only one or two cases of Q fever are diagnosed annually at Cambridge Clinical Microbiology and Public Health Laboratory despite serological screening of over 6000 patients with symptoms compatible with the disease annually. The source of infection in this case remains obscure, the patient giving no history of recognized risk factors. Reimer 4 has observed that the efficacy of antibiotic therapy is uncertain since most patients improve with or without treatment and the outcome for the small number of patients developing chronic or life-threatening infection has not been radically altered by antibiotic treatment. Furthermore, controlled clinical trials of antibiotics have not been performed. Clinical experience
Q Fever in Pregnancy
77
seems to accord with in vitro susceptibility but sensitivity delivering the fetus and placenta in a case of abortion is variable and occasional strains m a y be resistant. 4 attributed to maternal Q f e v e r / T h i s report prompted the The selection of an antimicrobial to treat this patient's measures described here to prevent such a case in our Q fever infection in pregnancy was problematic. The own unit. agents of first choice were both contraindicated: tetraPrevention of infection in staff followed the standard cyclines are associated with maternal hepatotoxicity, pan- precepts of eliminating the source of infection, increatitis, renal failure and fetal tooth discolouration and terrupting the route of transmission and enhancing host retarded skeletal bone growth, and the patient was al- resistance. Attention focused principally on the safe dislergic to erythromycin. There is little experience with posal of the possible source of infection, the products of alternative agents, all of which are also contraindicated conception, and avoidance of aerosolization of amniotic in pregnancy. fluid. Particulate respirator type face masks were worn Ciprofloxacin was chosen as in vitro sensitivity testing to offer some protection against inhalation of aerosolized has shown activity equivalent, or superior to con- C. burnetii. This type of mask gives approximately 99% ventional agents, 5 it has been used successfully in a case protection against experimental biological aerosols, conof Q fever endocarditis 6 and other rickettsial diseases. 7 ventional masks offer only approximately 10% protection Initial concerns of fetal toxicity with ciprofioxacin have under similar conditions (personal communication, Dr not been substantiated (Berkovitch et al. 8 and personal D. Rutter, Centre for Applied Microbiology and Research, evaluation based on data supplied by Bayer plc). Ci- Porton Down, Salisbury, Wiltshire, U.K.). The masks profloxacin crosses the placenta as readily as tetracycline resemble ordinary medical face masks, were acceptable or erythromycin, cord serum levels being 3 0 - 5 0 % of to both staff and patient and were comparatively cheap maternal serum levels for all three agents. (£2.17 each) and can be re-used. Fortunately, none The activity of antibiotics against C. burnetii is modest, of our staff were bearded, which renders these masks in vitro studies have shown individual agents achieve ineffectual. Such masks haven recently been rebacteriostasis only at relatively high concentrations. It is commended for health care workers exposed to patients noteworthy that viable organisms have been recovered with known or suspected infectious tuberculosis, ~4 alfrom the placenta in a case of Q fever in pregnancy though their value has been questioned, is We attempted despite 3 weeks prior treatment with 2 g per day of to enhance the resistance of staff to infection by an tetracycline, 9 and cotrimoxazole therapy has been sim- empirical course of doxycycline, there being no h u m a n ilarly ineffectual, 2 suggesting an analogy with Q fever vaccine against Q fever available in the U.K., although endocarditis, a chronic infection where antibiotic therapy an experimental vaccine is under development. In view is usually suppressive rather than curative. 4 It seems of the low incidence of h u m a n infection it is clearly likely that eradication of maternal infection can only be impractical to attempt to assemble a delivery team with achieved after the placenta has been expelled. Fluoro- natural immunity to O fever. quinolones are a m o n g the most active agents, yet the Q fever has established itself as a potentially serious levels achieved in our patient were below the MICso for infection in pregnancy due to a propensity for transC. burnetii 5 and insufficient to inhibit growth of C. burnetii placental infection of the fetus. The advice to pregnant in embryonated hens' eggs, although sufficient to inhibit women to avoid parturient sheep to minimize the risk of egg mortality. 1° There is evidence for synergy between maternal and consequent fetal infection with Chlamydia agents, the combination of ciprofloxacin and rifampicin psittaci 16 applies equally to C. burnetii and should be is batericidal in vitro 11 and in one series of Q fever extended to all livestock including parturient domestic endocarditis mortality was significantly reduced when p e t s . 17,18 doxycyline was combined with a quinolone, x2 In our case, however, the balance of risks to mother and fetus Acknowle@ements argued against the addition of a second agent. We are grateful to Mr P. Milton, Maternity, Gynaecological and Genetic The notoriety that Q fever has acquired for causing Services, Addenbrooke's NHS Trust for permission to report this case, h u m a n infection by the airborne route is probably at- Dr E. O. Caul, Bristol Public Health Laboratory for performing C. burnetii tributable to the low infecting dose, which can be as immunofluorescence tests and culture, to Dr D. Rutter, Centre for Applied Microbiology and Research, Porton Down, Salisbury and Dr. small as a single viable organism.13 Most h u m a n infection B. Bannister, Coppetts Wood Hospital, Muswell Hill for their advice in is asymptomatic, clinical infection is usually trivial and m a n a g i n g this case. self-limiting and person to person transmission is rare. 13 However, there has been a recent report of pneumonia References in an obstetrician who was believed to have acquired the ] Friedland JS, Jeffrey I, Griffin GE, Booker M, Courtenay-Evans R. Q infection from aerosolized infected amniotic fluid whilst lever and intrauterine death. Lancet 1994; 343: 288.
78
H. Ludlam et aL
2 Raoult D, Stein A, Q fever during pregnancy--a risk for women, fetuses, and obstetricians. N Engl J Med 1994; 330: 371. 3 Marrie TJ. Q fever in pregnancy: report of two cases. Infect Dis Clin Pract 1993; 2: 207-209. 4 Reimer LG. Q fever. Clin MicrobioI Rev 1993; 6: 193-198. 5 Yeaman MR, Mitscher LA, Baca OG. In vitro susceptibility of Coxiela burnetii to antibiotics, including several quinolones. Antimicrob Agents Chernother 1987; 31: 1079-1084. 6 Yebra M, Ortigosa J, Albarran t?, Crespo MC. Ciprofioxacin in a case of Q fever endocarditis. N Engl J Med 1990; 323: 614. 7 Raoult D, Callais H, De Micco P, Casanova P, Ciprofloxacin therapy for mediterranean spotted fever. Antimierob Agents Chemother 1986; 30: 606-607. 8 Berkovitch M, Pastuszak A, Gazarian M, Lewis M, Koren G. Safety of the new quinolones in pregnancy. Obstet Gynecol 1994; 84: 535-538. 9 Reichman N, Raz R, Keysary A, Goldwasser R, Flatau E. Chronic Q fever and severe thrombocytopenia in a pregnant woman. Am f Med 1988; 85: 253-254. 10 Keren G, Keysary A, Goldwasser R, Rubinstein E. The inhibitory effect of flouroquinolones on Coxiella burnetii growth in in-vitro systems. J Antimicrob Chemother 1994; 33: 1254-1255. 11 Yeaman MR, Roman MJ, Baca OG. Antibiotic susceptibilities of two
12 13 14
15
16 17 18
Coxiella burnetii isolates implicated in distinct clinical syndromes. Antimicrob Agents Chemother 1989; 33: 1052-1057. Levy PY, Drancourt M, Etienne J e t aL Comparison of different antibiotic regimens for therapy of 32 cases of Q fever endocarditis. Antimicrob Agents Chemother 1991; 35: 533-537. Marrie T]. Coxiella burnetii (Q fever). In: Mandell GL, Gordon Douglas R, Bennett JE, Eds. Principles and Practice of Infectious Diseases. 3rd Edn. New York: Churchill Livingstone, 1990; 1472-1476. Centres for Disease Control and Prevention. Guidelines for preventing the transmission of MlJcobacterium tuberculosis in health care facilities, 1994. MMWR Morb Mortal Wkly Rep, Recommendations and Reports. 1994; 43, No. RR-13. Adal KA, Anglim AM, Palumbo CL, Titus MG, Coyner BJ, Farr BM. The use of high-efficiency particulate air-filter respirators to protect hospital workers from tuberculosis. N EngI J Med 1994; 331: 169-173. Department of Health and Central Office of Information, 1991. While you are pregnant: safe eating and how to avoid infection from food and animals. Laughlin T, Waag D, Williams J, Marrie T. Q fever: from deer to dog to man. Lancet 1991; 337: 676-677. Marrie TJ, Durant H, Williams JC, Mintz E, Waag DM. Exposure to parturient cats: a risk factor for acquisition of Q fever in Maritime Canada. ] Infect Dis 1988; 158: 101-108.
CASE REPORT
Q Fever in Pregnancy H. Ludlam *~, T. G. W r e g h i t f , S. Thornton 2, B. J. Thomson 3, N. J. Bishop 4, S. Coomber 5 and J. Cunniffe ~ 1Clinical Microbiology and Public Health LaboratolN, 2University Department of Obstetrics and Gynaecology, 3Department of Medicine, 4University Department of Paediatrics, SDepartment of Occupational Health, Addenbrooke's NHS Trust, Cambridge CB2 20W, U.K. Accepted for publication 3 August 1996
We describe a case of acute symptomatic infection with Coxiella burnetii acquired between the 16th and 28th week of pregnancy. Oral ciprofloxacin therapy was started on diagnosis, at the 28th week of pregnanc!J, but symptoms were unabated after 3 weeks treatment, suggesting persisting infection of the products of conception. Caesarean section was therefore performed at 32 weeks gestation when a healthy infant was delivered, and subsequent investigations showed no evidence of transplacental spread of infection. Infection control measures were applied at the time of delivery to minimize the risk of infection to obstetricians and midwives from potentially infectious products of conception.
Introduction Coxiella burnetii is a well recognized cause of stillbirth and abortion in animals. H u m a n infection (0 fever) is usually acquired by inhalation of aerosols of excretions and secretions from infected animals, although ingestion of infected milk and tick bites are occasionally implicated. Exposure to parturient animals poses the greatest risk due to aerosolization of large numbers of organisms from infected amniotic fluid. H u m a n infection with C. burnetii in pregnancy has recently been linked to stillbirth and abortion. 1 The recent report of Q fever infection in an obstetrician delivering such a case 2 prompts us to report our own experience.
Case Report A 26-year-old pregnant nurse presented at 28 weeks gestation with a history of continuous malaise dating from the time of conception. She had also experienced four episodes of flu-like illness with sore throat, cough, fever, headaches and generalized musculoskeletal pains during this time. Physical examination was unremarkable and the chest X-ray was normal. There was no evidence of placental insufficiency and fetal development was normal. Haematological examination showed a slightly low haemoglobin (10.4 g/dl, normal non-pregnant range 11.5-16.5 g/dl) and a neutrophilia * Address correspondence to: H. Ludlam. 0163-4453/97/010075 +04 $12.00/0
10.4 X 109/1 (normal non-pregnant range 2.0-7.5 x 109/1). The serum C-Reactive protein (CRP) concentration was normal. Biochemical investigation showed hypoalbuminaemia (27.0g/1, normal non-pregnant range 3 0 . 0 - 5 1 . 0 g/l) and normal liver function tests apart from a raised bilirubin (28.0 ~tmol/1, normal non-pregnant range 2 . 0 - 1 7 . 0 gmol/l). Bacterial cultures from urine, blood and vagina did not reveal any pathogen. A diagnosis of acute Q fever was made on the basis of seroconversion to C. burnetii between the 16th and 2 8th week of pregnancy. The complement fixation test showed a rise in C. burnetii Phase 1 and 2 antibody titres from <8 to 64 and <8 to 256, respectively. The indirect immunofluorescence test (performed at Bristol Public Health Laboratory) showed a rise in C. burnetii IgG from <10 to > 1 2 8 0 and fgM from <10 to >1280. There was no serological evidence for recent infection with influenza A or B viruses, adenovirus, parvovirus, rubella virus, cytomegalovirus, chlamydia, Mycoplasma pneumoniae, Legionella pneumophila or Toxoplasma gondii. She gave a history of erythromycin allergy, confirmed by challenge which produced a generalized itchy rash. The patient refused to consider tetracycline therapy but agreed treatment with oral ciprofloxacin 5 0 0 m g bd. After 3 weeks ciprofloxacin therapy symptoms of malaise and generalized muscle pains continued unabated, suggesting persisting infection. The risk to mother and fetus of continuing the pregnancy was considered to be higher t h a n that of delivery and she was admitted for induction of labour at 32 weeks of pregnancy, local data showing © 1997 The British Society for the Study of Infection
76
H. Ludlam et aL
good neonatal outcome from this time onward. Induction of labour was unsuccessful and she proceeded to caesarean section 2 days later when a normal female infant weighing 1.88 kg was delivered. At the time of delivery, 2 h after the last dose of antibiotic, paired maternal serum and amniotic fluid ciprofloxacin levels were 0.9mg/1 and 0.5mg/1, respectively. The serum ciprofloxacin level in cord blood taken 3 h after the last maternal dose was 0.4 mg/1. In view of the maternal history and oxygen dependency the neonate received broad spectrum parental antibiotic therapy with penicillin, erythromycin and ciprofloxacin immediately after delivery. Haematological investigation was unremarkable, the ESR and CRP were normal and there were no biochemical abnormalities. The penicillin was stopped after 5 days when blood and surveillance cultures proved negative, but the erythromycin and ciprofloxacin were continued for a total of 2 weeks in view of the possibility of transplacental transmission of Q fever. However, serological investigation of the infant showed no evidence of fetal infection, cord blood taken at delivery being negative for C. burnetii IgM. Histological examination of placental sections revealed no abnormality with no evidence of past or current infection and immunocytochemical staining and culture of placenta were negative for C. burnetii. Following delivery, the mother's ciprofloxacin was discontinued and doxycycline 100 mg bd was prescribed for a further 2 weeks and symptoms slowly resolved thereafter. At review 4 weeks after delivery mother and baby were both well; 6 months after delivery, the mother's C. burnetii Phase 1 and 2 antibody titres had fallen fourfold compared with the titres at presentation.
Infection control and staff surveillance Non-essential staff were excluded from the delivery suite during labour. Although we attempted to exclude staff with conditions known to predispose to more serious infection (the pregnant, the immunocompromised or those with cardiovascular abnormalities) one obstetrician with a ventricular septal defect assisted at delivery. Staff present at delivery wore gloves and gowns as usual but in addition safety spectacles and 3M 8822 particulate respirator type face masks (Tower Supplies, Poole, Dorset) were worn. The possibility of aerosolization of Q fever organisms present in amniotic fluid was minimized by mopping the fluid as it emerged with swabs, careful handling of the placenta to avoid splashing and towelling the baby immediately after delivery. Clinical waste was disposed in accordance with local
guidelines for 'infection risk from blood', surfaces contaminated with amniotic fluid were disinfected with sodium hypochlorite. Delivery took place in the usual suites. No special arrangements were made other than allowing 3 h normal ventilation before re-use. No further infection control measures were applied to mother and baby following delivery. The 10 members of staff who were present during labour, and the husband who was also present, were offered, and accepted, prophylaxis with doxycycline 200 mg once daily for 7 days. All were asked to report any illness in the following 6 weeks. The member of staff with the ventricular septal defect received 1 months prophylaxis and was followed up for a total of 12 weeks. None reported any illness suggestive of Q fever. Serum samples were taken from the staff delivering the baby and placenta (three obstetricians, one midwife, one paediatrician and one obstetric theatre scrub nurse) at the time of delivery and 6 weeks later; none had antibodies to C. burnetii.
Discussion Raoult and Stein 2 in a review of the literature to 1994 recorded 15 published cases of Q fever in pregnancy. The outcome of pregnancy was normal in five cases, prematurity and low birth weight were noted in seven cases and fetal death in utero occurred in three cases. C. burnetii was isolated from six of 11 placentas. Infection in pregnancy may be primary or due to reactivation of a previous infection and the course may be acute or chronic. Infection of the products of conception is particularly liable to lead to chronic infeciton. 3 The serological response in our case indicated an acute infection acquired during pregnancy with no evidence for involvement of the products of conception. The prevalence of Q fever in our area is unknown but it is likely to be low as there is little local farming of livestock; only one or two cases of Q fever are diagnosed annually at Cambridge Clinical Microbiology and Public Health Laboratory despite serological screening of over 6000 patients with symptoms compatible with the disease annually. The source of infection in this case remains obscure, the patient giving no history of recognized risk factors. Reimer 4 has observed that the efficacy of antibiotic therapy is uncertain since most patients improve with or without treatment and the outcome for the small number of patients developing chronic or life-threatening infection has not been radically altered by antibiotic treatment. Furthermore, controlled clinical trials of antibiotics have not been performed. Clinical experience
Q Fever in Pregnancy
77
seems to accord with in vitro susceptibility but sensitivity delivering the fetus and placenta in a case of abortion is variable and occasional strains m a y be resistant. 4 attributed to maternal Q f e v e r / T h i s report prompted the The selection of an antimicrobial to treat this patient's measures described here to prevent such a case in our Q fever infection in pregnancy was problematic. The own unit. agents of first choice were both contraindicated: tetraPrevention of infection in staff followed the standard cyclines are associated with maternal hepatotoxicity, pan- precepts of eliminating the source of infection, increatitis, renal failure and fetal tooth discolouration and terrupting the route of transmission and enhancing host retarded skeletal bone growth, and the patient was al- resistance. Attention focused principally on the safe dislergic to erythromycin. There is little experience with posal of the possible source of infection, the products of alternative agents, all of which are also contraindicated conception, and avoidance of aerosolization of amniotic in pregnancy. fluid. Particulate respirator type face masks were worn Ciprofloxacin was chosen as in vitro sensitivity testing to offer some protection against inhalation of aerosolized has shown activity equivalent, or superior to con- C. burnetii. This type of mask gives approximately 99% ventional agents, 5 it has been used successfully in a case protection against experimental biological aerosols, conof Q fever endocarditis 6 and other rickettsial diseases. 7 ventional masks offer only approximately 10% protection Initial concerns of fetal toxicity with ciprofioxacin have under similar conditions (personal communication, Dr not been substantiated (Berkovitch et al. 8 and personal D. Rutter, Centre for Applied Microbiology and Research, evaluation based on data supplied by Bayer plc). Ci- Porton Down, Salisbury, Wiltshire, U.K.). The masks profloxacin crosses the placenta as readily as tetracycline resemble ordinary medical face masks, were acceptable or erythromycin, cord serum levels being 3 0 - 5 0 % of to both staff and patient and were comparatively cheap maternal serum levels for all three agents. (£2.17 each) and can be re-used. Fortunately, none The activity of antibiotics against C. burnetii is modest, of our staff were bearded, which renders these masks in vitro studies have shown individual agents achieve ineffectual. Such masks haven recently been rebacteriostasis only at relatively high concentrations. It is commended for health care workers exposed to patients noteworthy that viable organisms have been recovered with known or suspected infectious tuberculosis, ~4 alfrom the placenta in a case of Q fever in pregnancy though their value has been questioned, is We attempted despite 3 weeks prior treatment with 2 g per day of to enhance the resistance of staff to infection by an tetracycline, 9 and cotrimoxazole therapy has been sim- empirical course of doxycycline, there being no h u m a n ilarly ineffectual, 2 suggesting an analogy with Q fever vaccine against Q fever available in the U.K., although endocarditis, a chronic infection where antibiotic therapy an experimental vaccine is under development. In view is usually suppressive rather than curative. 4 It seems of the low incidence of h u m a n infection it is clearly likely that eradication of maternal infection can only be impractical to attempt to assemble a delivery team with achieved after the placenta has been expelled. Fluoro- natural immunity to O fever. quinolones are a m o n g the most active agents, yet the Q fever has established itself as a potentially serious levels achieved in our patient were below the MICso for infection in pregnancy due to a propensity for transC. burnetii 5 and insufficient to inhibit growth of C. burnetii placental infection of the fetus. The advice to pregnant in embryonated hens' eggs, although sufficient to inhibit women to avoid parturient sheep to minimize the risk of egg mortality. 1° There is evidence for synergy between maternal and consequent fetal infection with Chlamydia agents, the combination of ciprofloxacin and rifampicin psittaci 16 applies equally to C. burnetii and should be is batericidal in vitro 11 and in one series of Q fever extended to all livestock including parturient domestic endocarditis mortality was significantly reduced when p e t s . 17,18 doxycyline was combined with a quinolone, x2 In our case, however, the balance of risks to mother and fetus Acknowle@ements argued against the addition of a second agent. We are grateful to Mr P. Milton, Maternity, Gynaecological and Genetic The notoriety that Q fever has acquired for causing Services, Addenbrooke's NHS Trust for permission to report this case, h u m a n infection by the airborne route is probably at- Dr E. O. Caul, Bristol Public Health Laboratory for performing C. burnetii tributable to the low infecting dose, which can be as immunofluorescence tests and culture, to Dr D. Rutter, Centre for Applied Microbiology and Research, Porton Down, Salisbury and Dr. small as a single viable organism.13 Most h u m a n infection B. Bannister, Coppetts Wood Hospital, Muswell Hill for their advice in is asymptomatic, clinical infection is usually trivial and m a n a g i n g this case. self-limiting and person to person transmission is rare. 13 However, there has been a recent report of pneumonia References in an obstetrician who was believed to have acquired the ] Friedland JS, Jeffrey I, Griffin GE, Booker M, Courtenay-Evans R. Q infection from aerosolized infected amniotic fluid whilst lever and intrauterine death. Lancet 1994; 343: 288.
78
H. Ludlam et aL
2 Raoult D, Stein A, Q fever during pregnancy--a risk for women, fetuses, and obstetricians. N Engl J Med 1994; 330: 371. 3 Marrie TJ. Q fever in pregnancy: report of two cases. Infect Dis Clin Pract 1993; 2: 207-209. 4 Reimer LG. Q fever. Clin MicrobioI Rev 1993; 6: 193-198. 5 Yeaman MR, Mitscher LA, Baca OG. In vitro susceptibility of Coxiela burnetii to antibiotics, including several quinolones. Antimicrob Agents Chernother 1987; 31: 1079-1084. 6 Yebra M, Ortigosa J, Albarran t?, Crespo MC. Ciprofioxacin in a case of Q fever endocarditis. N Engl J Med 1990; 323: 614. 7 Raoult D, Callais H, De Micco P, Casanova P, Ciprofloxacin therapy for mediterranean spotted fever. Antimierob Agents Chemother 1986; 30: 606-607. 8 Berkovitch M, Pastuszak A, Gazarian M, Lewis M, Koren G. Safety of the new quinolones in pregnancy. Obstet Gynecol 1994; 84: 535-538. 9 Reichman N, Raz R, Keysary A, Goldwasser R, Flatau E. Chronic Q fever and severe thrombocytopenia in a pregnant woman. Am f Med 1988; 85: 253-254. 10 Keren G, Keysary A, Goldwasser R, Rubinstein E. The inhibitory effect of flouroquinolones on Coxiella burnetii growth in in-vitro systems. J Antimicrob Chemother 1994; 33: 1254-1255. 11 Yeaman MR, Roman MJ, Baca OG. Antibiotic susceptibilities of two
12 13 14
15
16 17 18
Coxiella burnetii isolates implicated in distinct clinical syndromes. Antimicrob Agents Chemother 1989; 33: 1052-1057. Levy PY, Drancourt M, Etienne J e t aL Comparison of different antibiotic regimens for therapy of 32 cases of Q fever endocarditis. Antimicrob Agents Chemother 1991; 35: 533-537. Marrie T]. Coxiella burnetii (Q fever). In: Mandell GL, Gordon Douglas R, Bennett JE, Eds. Principles and Practice of Infectious Diseases. 3rd Edn. New York: Churchill Livingstone, 1990; 1472-1476. Centres for Disease Control and Prevention. Guidelines for preventing the transmission of MlJcobacterium tuberculosis in health care facilities, 1994. MMWR Morb Mortal Wkly Rep, Recommendations and Reports. 1994; 43, No. RR-13. Adal KA, Anglim AM, Palumbo CL, Titus MG, Coyner BJ, Farr BM. The use of high-efficiency particulate air-filter respirators to protect hospital workers from tuberculosis. N EngI J Med 1994; 331: 169-173. Department of Health and Central Office of Information, 1991. While you are pregnant: safe eating and how to avoid infection from food and animals. Laughlin T, Waag D, Williams J, Marrie T. Q fever: from deer to dog to man. Lancet 1991; 337: 676-677. Marrie TJ, Durant H, Williams JC, Mintz E, Waag DM. Exposure to parturient cats: a risk factor for acquisition of Q fever in Maritime Canada. ] Infect Dis 1988; 158: 101-108.