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Prolonged use of a diaphragm and toxic shock syndrome
Vol. 38, No.2, August 1982
FERTILITY AND STERILITY Copyright 0 1982 The American Fertility Society
Printed in U.8A.
Prolonged use of a diaphragm and toxic shock syndrome
Elizabeth A. Baehler, M.D.* William P. Dillon, M.D.* Thomas J. Cumbo, M.D.t Richard V. Lee, M.D.:j: State University of New York at Buffalo School of Medicine and Children's Hospital of Buffalo, Buffalo, New York
Toxic shock syndrome (TSS) is an acute febrile exanthematous illness associated with toxinproducing staphylococci. It has been the object of considerable attention in the past 4 years because of the recognition of an association with the use of intravaginal tampons' during menstruation. 1 Currently the diagnostic criteria for TSS include fever (temperature;;;': 38.9° C), diffuse erythroderma followed by desquamation, especially of the palms and soles, hypotension, and abnormalities of three or more organ systems. 2 Clinical syndromes produced by toxin-producing staphylococci have been known since the beginning ofthe . 20th century. TSS incorporates features of all these syndromes, suggesting that more than one toxin is involved. The interrelationships among these toxins and the host immune response in the pathogenesis of florid TSS and less "classic" illness-accompanying Staphylococcus aureus infections of the genital tract are unclear. The emphasis upon TSS as a discrete clinical entity may obscure the heterogeneous clinical presentation produced by two or more staphylococcal toxins and divert the physician's attention from recognizing possible S. aureus-associated disease and instituting adequate and aggressive
Received February 22, 1982; revised and accepted April 16, 1982. *Department of Obstetrics an<,l Gynecology, School of Medicine, State University of New York at Buffalo. tDepartment of Medicine, School of Medicine, State University of New York at Buffalo. :j:Reprint requests: Richard V. Lee, M.D., Chief, Department of Medicine, Children's Hospital of Buffalo, 219 Bryant Street, Buffalo, New York 14222. 248
Baehler et aI. Communications-in-brief
supportive therapy, particularly volume replacement. 3 , 4 Obtaining and properly interpreting appropriate cultures for S. aureus when there are focal lesions is a valuable adjunct, since the initiation of anti staphylococcal antibiotic therapy, while not curative ofTSS, does assist in reduction of the number of microorganisms and in the prevention of recurrence ofTSS.1-4 The importance of genital tract toxin-producing S. aureus as a cause of clinical manifestations with multiple clinical predisposing factors rather than a single syndrome is emphasized. 1-4 TSS is not exclusively found in tampon-using menstruating women. A review of a smaller number of cases includes men, women, and children, of all ages, and reports either localized S. aureus .infection such as that of surgical wounds or recent childbirth, either vaginally or by cesarian section, with a median incubation in postoperative cases of 2 days.4 The following case, involving the extended use of a contraceptive diaphragm, illustrates the difficulties in promptly establishing a clinical diagnosis of staphylococcal toxin syndromes. CASE REPORT
A 27-year-old woman, G2PIOll, was admitted to the hospital after 24 hours of fever, shaking chills, sweats, nausea and vomiting, and diminished urine output. She was 2 months postpartum. She had been unable to remove a new coil-spring diaphragm, used for the first time since parturition, for 3% days before admission. The diaphragm was removed with some difficulty by her physician earlier on the day of admission. Fertility and Sterility
A purulent, fQul-smelling vaginal discharge was nQted by her physician at the time the diaphragm was extracted and by the patient afterwards. She was lactating and had had nO' menses since cQnceptiQn. Her past medical histQry was unremarkable except fQr mitral valve prolapse. The patient had never had any sexually transmitted infectiQns Qr pelvic inflammatQry disease. A diaphragm had been used in the past withQut any prQblems. FQreign travel, allergies, camping, and change in diet were denied. EvaluatiQn at the time Qf admissiQn was remarkable fQr a pulse rate Qf 120 beats per minute and QrthQstaticlightheadedness. The blQQd pressure was 110170 mmHg when the patient was supine and fell less than 15 mm Hg systQlic when she was seated. The temperature was 39.40 C. Skin and Qral mUCQsawere nQrmal except fQr a "strawberry tQngue." Pelvic examinatiQn was nQrmal except fQr a yellQw, fQul-smelling vaginal discharge and markedly erythematQus vaginal mucQsaand cervix. Other than the click-murmur Qf mitral valve prQlapse, the remainder Qf the physical examinatiQn was unrevealing. Within 12hQurs fQllQwing admissiQn the patient develQped a generalized "sunburn-like" erythematQus, macular, nQnpruritic rash. The white blQQd cell CQunt was 17,000, with 63% segmented and 33% juvenile PQlymQrphQnuclear leukQcytes. The sedimentatiQn rate was 45 mmlhr. The results Qf hemQgIQbin, platelet, and clQtting studies were nQrmal, as were the results QfblQod urea nitrQgen, electrQlyte, and liver functiQn tests. The electrQcardiQgram shQwedQnly sinus tachycardia. A chest x-ray was nQrmal. Multiple cultures Qf vagina, thrQat, urine, and blQQd were Qbtained. The vaginal culture grew cQagulase-PQsitive S. aureus resistant to' penicillin G and ampicillin. The urine culture. grew 30,000 cQlIml cQagulase-PQsitive S. aureus with the same antibiQtic resistance. All Qther cultures grew nQrmal flQra Qr nQthing. Acute and CQnvalescent serum samples fQr RQcky MQuntain sPQtted fever, measles, and leptQspirQsisshQwed nO' change in titer. VigQrQus intravenQUS fluid and electrQlyte therapy was administered and, in additiQn, the patient was initially begun Qn ampicillin and tQbramycin. ShQrtly after the appearance Qf the rash, staphylQcQccal TSS W-as suspected, and the ampicillin was changed to' Qxacillin. The rash and strawberry tQngue faded within 24 hQurs, and she became nQrmQtensive and afebrile by the secQnd hQspital day. She was changed to' Qral diclQxacilVol. 38, No.2, August 1982
lin as the Qnly antibiQtic Qn the fQurth hQspital day, after the culture results were cQnfirmed. At the time Qf discharge Qn the sixth hQspital day, desquamatiQn Qf the skin Qn the palms and sQles had started and cQntinued fQr anQther 7 to' 10 days. A 10-day CQurse Qf diclQxacillin was CQmpleted. FQllQw-up vaginal, cervical, and pharyngeal cultures 3 and 5 mQnths later cQntained nO' S. aureus.The patient had resumed menstruatiQn but was nQt using tampQns Qr a diaphragm.
DISCUSSION
This patient meets the definitive criteria fQr TSS.2 She had high fever, QrthQstatic hYPQtensiQn, an evanescent rash fQllQwedby desquamatiQn, and indicatiQns Qf invQlvement Qf three Qrgan systems (gastrQintestinal, genitQurinary,and skin and mUCQUS membranes). These·manifestatiQns were nQt all simultaneQusly present during the first· 36 hQurs Qf her disease, hQwever,and SQme were Qf sufficiently shQrt duratiQn that they might have been QverlQQked. MQreQver, the patient was nQt menstruating and was nQt using tampQns. The diagnQsis CQuid easily have been missed and, in fact, wasnQt suspected until after· the appearance Qf the rash. EarlydiagnQsis is impQrtant. Illness caused by staphylococcaltQxinscanprQgress rapidly to' irretrievable shQck. The cQmbinatiQn Qfthe prQIQnged presence Qf a vaginal fQreign bQdy, such as a diaphragm Qr tampQn, an abnQrmal vaginal discharge, and marked erythema Qfthe vaginal muCQsa is a useful indicatQr fQr the presence QftQxinprQducing staphylQcQcci in the IQwer genital tract. The pathQgenesis Qf TSS is presumably dependent UPQn cQIQnizatiQn with S. aureus strains capable Qf elabQratingtQxins. The events that initiate tQxin prQductiQn in sufficient quantity to' prQduce IQcal effects and systemic absQrptiQn· are nQt certain. HQwever,menstruatiQn and nQrmal PQstpartum IQchia are. CQmmQn features, alQng with the use Qf vaginalfQreign bQdies that can prQduce IQcal excQriatiQns, 5 retard clearance Qf secretiQns, and alter the vaginal pH, thereby fQStering the prQductiQn and absQrptiQn Qf staphylQcQccal tQxins. EpidemiQIQgic data suggest that superabsQrbent tampQns fQster the develQpment Qf TSS because WQmen may leave them in place much IQnger than regular tampQns .. Similarly, a few cases Qf TSS assQciated with diaphragm use have fQllQwed prQIQnged retentiQn Qf the diaphragm,36 hQurs Qr IQnger. 6 Baehler et aI. Communications-in-brief
249
This clinical experience suggests that there is a spectrum of severity and organ involvement resuiting· from toxin production by staphylococci. TSS represents the most severe situation. The variable clinical manifestations of staphylococcal toxin disease may reflect the type of toxin produced and absorbed. Changing local conditions in the vagina may influence the sequence of production and the quantity in which toxins are produced and thus determine the progression of the clinical syndrome. The appearance of the effects of any of these staphylococcal toxins is cause for careful evaluation of the patient, including estimation of the hematologic, hepatic, muscular, metabolic, and renal function and cervical and vaginal cultures for S. aureus. 2 These patients should receive aggressive supportive therapy and, in addition, antistaphylococcal antibiotics in order to decrease the number of microorganisms and minimize recurrence. Because of the high prevalence of penicillinase~producing staphylococci, betalactamase-resistant penicillins such as oxacillin, nafcillin, and dicloxacillin are preferred. In the penicillin-allergic patient a cephalosporin or vancomycin should be used. The rarity of staphylococcal toxin diseases in users of vaginal barrier contraceptives may be related to the concomitant use of spermicides. There have been claims of antibacterial, antiviral, and antifungal activity ofspermicides. 7 The use of agents .that retard bacterial growth· may increase the length of time a barrier device can be retained before bacterial multiplication and toxin production begin. Hence, retention ofa diaphragm for 12 to 18 hours may be relatively safe, whereas prolonged use for 36 hours or more without replenishing the spermicide may increase the risk of toxin-mediated illness. Investigation of possible spermicidal inhibition of staphylococcal colonization may be warranted. That patients fail to recognize the potential danger of retaining a diaphragm beyond the recommended 24 hours, as illustrated by this case, suggests that guidelines similar to those now rec-
250
Baehler et al.. Communications-in-brief
ommended by the Center for Disease Control for tampons should be developed. Moreover, many women use their diaphragms during menses. Directions to users for insertion, cleansing, and storage of the diaphragm should be reevaluated. Many nations with population problems are seeking inexpensive, simple forms of contraception typified by mechanical barriers. New vaginal contraceptive technology 8 includes collagen sponges and cervical caps. Physicians should urge caution about the extended use of any vaginal foreign body. SUMMARY
TSS has been most frequently described in menstruating women. It has been associated with lower genital tract carriage of S. aureus and with the use of highly absorbent tampons. This report demonstrates the appearance of the distinctive clinical syndrome associated with staphylococcal toxins following the prolonged use of a diaphragm by a nonmenstruating woman. Increased vigilance for the potential dangers of using vaginal occlusive devices when the lower genital tract is colonized by S. aureus is urged. REFERENCES 1. Shands KN; Schmid GP, DanBB, Blum D; Guidotti R.I, Hargrett NT,. Anderson RL, Hill DL,. Broome CV, Band JD, Fraser DW: Toxic-shack syndrome in menstruating· women. N Engl J Med 303:1436, 1980 . 2. Tofte RW; Williams DN: Toxic shook syndrome: evidence of a broad clinical spectrum. JAMA 246:2163, 1981 3. Larsen B, Schlievert PM: TSS: the mystery unfoldsi Contemp Obstet Gynecol 18:219, 1981 4. Reingold AL, Dan BB, Shands KN, Broome CV: Toxicshock syndrome not associated with menstruation. Lancet 1:1, 1982 5. Friedrich EG, Siegesmund KA: Tampon-associated vaginal ulcerations. Obstet Gynecol 55:149,1980 6. Loomis L, Feder HM: Toxic-shock syndrome associated with diaphragm use. N Engl J Med 305:1585,1981 7. Cutler JC: Spermicides as prophylaxis against sexually transmissible diseases (STDs). IPPF Med Bull 13:3, 1979 8. Tatum HJ, Connell-Tatum EB: Barrier contraception: a comprehensive overview..Fertil SteriI36:1, 1981.
Fertility and Sterility .
FERTILITY AND STERILITY Copyright 0 1982 The American Fertility Society
Printed in U.8A.
Prolonged use of a diaphragm and toxic shock syndrome
Elizabeth A. Baehler, M.D.* William P. Dillon, M.D.* Thomas J. Cumbo, M.D.t Richard V. Lee, M.D.:j: State University of New York at Buffalo School of Medicine and Children's Hospital of Buffalo, Buffalo, New York
Toxic shock syndrome (TSS) is an acute febrile exanthematous illness associated with toxinproducing staphylococci. It has been the object of considerable attention in the past 4 years because of the recognition of an association with the use of intravaginal tampons' during menstruation. 1 Currently the diagnostic criteria for TSS include fever (temperature;;;': 38.9° C), diffuse erythroderma followed by desquamation, especially of the palms and soles, hypotension, and abnormalities of three or more organ systems. 2 Clinical syndromes produced by toxin-producing staphylococci have been known since the beginning ofthe . 20th century. TSS incorporates features of all these syndromes, suggesting that more than one toxin is involved. The interrelationships among these toxins and the host immune response in the pathogenesis of florid TSS and less "classic" illness-accompanying Staphylococcus aureus infections of the genital tract are unclear. The emphasis upon TSS as a discrete clinical entity may obscure the heterogeneous clinical presentation produced by two or more staphylococcal toxins and divert the physician's attention from recognizing possible S. aureus-associated disease and instituting adequate and aggressive
Received February 22, 1982; revised and accepted April 16, 1982. *Department of Obstetrics an<,l Gynecology, School of Medicine, State University of New York at Buffalo. tDepartment of Medicine, School of Medicine, State University of New York at Buffalo. :j:Reprint requests: Richard V. Lee, M.D., Chief, Department of Medicine, Children's Hospital of Buffalo, 219 Bryant Street, Buffalo, New York 14222. 248
Baehler et aI. Communications-in-brief
supportive therapy, particularly volume replacement. 3 , 4 Obtaining and properly interpreting appropriate cultures for S. aureus when there are focal lesions is a valuable adjunct, since the initiation of anti staphylococcal antibiotic therapy, while not curative ofTSS, does assist in reduction of the number of microorganisms and in the prevention of recurrence ofTSS.1-4 The importance of genital tract toxin-producing S. aureus as a cause of clinical manifestations with multiple clinical predisposing factors rather than a single syndrome is emphasized. 1-4 TSS is not exclusively found in tampon-using menstruating women. A review of a smaller number of cases includes men, women, and children, of all ages, and reports either localized S. aureus .infection such as that of surgical wounds or recent childbirth, either vaginally or by cesarian section, with a median incubation in postoperative cases of 2 days.4 The following case, involving the extended use of a contraceptive diaphragm, illustrates the difficulties in promptly establishing a clinical diagnosis of staphylococcal toxin syndromes. CASE REPORT
A 27-year-old woman, G2PIOll, was admitted to the hospital after 24 hours of fever, shaking chills, sweats, nausea and vomiting, and diminished urine output. She was 2 months postpartum. She had been unable to remove a new coil-spring diaphragm, used for the first time since parturition, for 3% days before admission. The diaphragm was removed with some difficulty by her physician earlier on the day of admission. Fertility and Sterility
A purulent, fQul-smelling vaginal discharge was nQted by her physician at the time the diaphragm was extracted and by the patient afterwards. She was lactating and had had nO' menses since cQnceptiQn. Her past medical histQry was unremarkable except fQr mitral valve prolapse. The patient had never had any sexually transmitted infectiQns Qr pelvic inflammatQry disease. A diaphragm had been used in the past withQut any prQblems. FQreign travel, allergies, camping, and change in diet were denied. EvaluatiQn at the time Qf admissiQn was remarkable fQr a pulse rate Qf 120 beats per minute and QrthQstaticlightheadedness. The blQQd pressure was 110170 mmHg when the patient was supine and fell less than 15 mm Hg systQlic when she was seated. The temperature was 39.40 C. Skin and Qral mUCQsawere nQrmal except fQr a "strawberry tQngue." Pelvic examinatiQn was nQrmal except fQr a yellQw, fQul-smelling vaginal discharge and markedly erythematQus vaginal mucQsaand cervix. Other than the click-murmur Qf mitral valve prQlapse, the remainder Qf the physical examinatiQn was unrevealing. Within 12hQurs fQllQwing admissiQn the patient develQped a generalized "sunburn-like" erythematQus, macular, nQnpruritic rash. The white blQQd cell CQunt was 17,000, with 63% segmented and 33% juvenile PQlymQrphQnuclear leukQcytes. The sedimentatiQn rate was 45 mmlhr. The results Qf hemQgIQbin, platelet, and clQtting studies were nQrmal, as were the results QfblQod urea nitrQgen, electrQlyte, and liver functiQn tests. The electrQcardiQgram shQwedQnly sinus tachycardia. A chest x-ray was nQrmal. Multiple cultures Qf vagina, thrQat, urine, and blQQd were Qbtained. The vaginal culture grew cQagulase-PQsitive S. aureus resistant to' penicillin G and ampicillin. The urine culture. grew 30,000 cQlIml cQagulase-PQsitive S. aureus with the same antibiQtic resistance. All Qther cultures grew nQrmal flQra Qr nQthing. Acute and CQnvalescent serum samples fQr RQcky MQuntain sPQtted fever, measles, and leptQspirQsisshQwed nO' change in titer. VigQrQus intravenQUS fluid and electrQlyte therapy was administered and, in additiQn, the patient was initially begun Qn ampicillin and tQbramycin. ShQrtly after the appearance Qf the rash, staphylQcQccal TSS W-as suspected, and the ampicillin was changed to' Qxacillin. The rash and strawberry tQngue faded within 24 hQurs, and she became nQrmQtensive and afebrile by the secQnd hQspital day. She was changed to' Qral diclQxacilVol. 38, No.2, August 1982
lin as the Qnly antibiQtic Qn the fQurth hQspital day, after the culture results were cQnfirmed. At the time Qf discharge Qn the sixth hQspital day, desquamatiQn Qf the skin Qn the palms and sQles had started and cQntinued fQr anQther 7 to' 10 days. A 10-day CQurse Qf diclQxacillin was CQmpleted. FQllQw-up vaginal, cervical, and pharyngeal cultures 3 and 5 mQnths later cQntained nO' S. aureus.The patient had resumed menstruatiQn but was nQt using tampQns Qr a diaphragm.
DISCUSSION
This patient meets the definitive criteria fQr TSS.2 She had high fever, QrthQstatic hYPQtensiQn, an evanescent rash fQllQwedby desquamatiQn, and indicatiQns Qf invQlvement Qf three Qrgan systems (gastrQintestinal, genitQurinary,and skin and mUCQUS membranes). These·manifestatiQns were nQt all simultaneQusly present during the first· 36 hQurs Qf her disease, hQwever,and SQme were Qf sufficiently shQrt duratiQn that they might have been QverlQQked. MQreQver, the patient was nQt menstruating and was nQt using tampQns. The diagnQsis CQuid easily have been missed and, in fact, wasnQt suspected until after· the appearance Qf the rash. EarlydiagnQsis is impQrtant. Illness caused by staphylococcaltQxinscanprQgress rapidly to' irretrievable shQck. The cQmbinatiQn Qfthe prQIQnged presence Qf a vaginal fQreign bQdy, such as a diaphragm Qr tampQn, an abnQrmal vaginal discharge, and marked erythema Qfthe vaginal muCQsa is a useful indicatQr fQr the presence QftQxinprQducing staphylQcQcci in the IQwer genital tract. The pathQgenesis Qf TSS is presumably dependent UPQn cQIQnizatiQn with S. aureus strains capable Qf elabQratingtQxins. The events that initiate tQxin prQductiQn in sufficient quantity to' prQduce IQcal effects and systemic absQrptiQn· are nQt certain. HQwever,menstruatiQn and nQrmal PQstpartum IQchia are. CQmmQn features, alQng with the use Qf vaginalfQreign bQdies that can prQduce IQcal excQriatiQns, 5 retard clearance Qf secretiQns, and alter the vaginal pH, thereby fQStering the prQductiQn and absQrptiQn Qf staphylQcQccal tQxins. EpidemiQIQgic data suggest that superabsQrbent tampQns fQster the develQpment Qf TSS because WQmen may leave them in place much IQnger than regular tampQns .. Similarly, a few cases Qf TSS assQciated with diaphragm use have fQllQwed prQIQnged retentiQn Qf the diaphragm,36 hQurs Qr IQnger. 6 Baehler et aI. Communications-in-brief
249
This clinical experience suggests that there is a spectrum of severity and organ involvement resuiting· from toxin production by staphylococci. TSS represents the most severe situation. The variable clinical manifestations of staphylococcal toxin disease may reflect the type of toxin produced and absorbed. Changing local conditions in the vagina may influence the sequence of production and the quantity in which toxins are produced and thus determine the progression of the clinical syndrome. The appearance of the effects of any of these staphylococcal toxins is cause for careful evaluation of the patient, including estimation of the hematologic, hepatic, muscular, metabolic, and renal function and cervical and vaginal cultures for S. aureus. 2 These patients should receive aggressive supportive therapy and, in addition, antistaphylococcal antibiotics in order to decrease the number of microorganisms and minimize recurrence. Because of the high prevalence of penicillinase~producing staphylococci, betalactamase-resistant penicillins such as oxacillin, nafcillin, and dicloxacillin are preferred. In the penicillin-allergic patient a cephalosporin or vancomycin should be used. The rarity of staphylococcal toxin diseases in users of vaginal barrier contraceptives may be related to the concomitant use of spermicides. There have been claims of antibacterial, antiviral, and antifungal activity ofspermicides. 7 The use of agents .that retard bacterial growth· may increase the length of time a barrier device can be retained before bacterial multiplication and toxin production begin. Hence, retention ofa diaphragm for 12 to 18 hours may be relatively safe, whereas prolonged use for 36 hours or more without replenishing the spermicide may increase the risk of toxin-mediated illness. Investigation of possible spermicidal inhibition of staphylococcal colonization may be warranted. That patients fail to recognize the potential danger of retaining a diaphragm beyond the recommended 24 hours, as illustrated by this case, suggests that guidelines similar to those now rec-
250
Baehler et al.. Communications-in-brief
ommended by the Center for Disease Control for tampons should be developed. Moreover, many women use their diaphragms during menses. Directions to users for insertion, cleansing, and storage of the diaphragm should be reevaluated. Many nations with population problems are seeking inexpensive, simple forms of contraception typified by mechanical barriers. New vaginal contraceptive technology 8 includes collagen sponges and cervical caps. Physicians should urge caution about the extended use of any vaginal foreign body. SUMMARY
TSS has been most frequently described in menstruating women. It has been associated with lower genital tract carriage of S. aureus and with the use of highly absorbent tampons. This report demonstrates the appearance of the distinctive clinical syndrome associated with staphylococcal toxins following the prolonged use of a diaphragm by a nonmenstruating woman. Increased vigilance for the potential dangers of using vaginal occlusive devices when the lower genital tract is colonized by S. aureus is urged. REFERENCES 1. Shands KN; Schmid GP, DanBB, Blum D; Guidotti R.I, Hargrett NT,. Anderson RL, Hill DL,. Broome CV, Band JD, Fraser DW: Toxic-shack syndrome in menstruating· women. N Engl J Med 303:1436, 1980 . 2. Tofte RW; Williams DN: Toxic shook syndrome: evidence of a broad clinical spectrum. JAMA 246:2163, 1981 3. Larsen B, Schlievert PM: TSS: the mystery unfoldsi Contemp Obstet Gynecol 18:219, 1981 4. Reingold AL, Dan BB, Shands KN, Broome CV: Toxicshock syndrome not associated with menstruation. Lancet 1:1, 1982 5. Friedrich EG, Siegesmund KA: Tampon-associated vaginal ulcerations. Obstet Gynecol 55:149,1980 6. Loomis L, Feder HM: Toxic-shock syndrome associated with diaphragm use. N Engl J Med 305:1585,1981 7. Cutler JC: Spermicides as prophylaxis against sexually transmissible diseases (STDs). IPPF Med Bull 13:3, 1979 8. Tatum HJ, Connell-Tatum EB: Barrier contraception: a comprehensive overview..Fertil SteriI36:1, 1981.
Fertility and Sterility .