Search PubMed⌕ Search

Biomedical subjects

R B Nadelman

Publications and source records attributed to R B Nadelman.

At least 55 records · Page 3Linked to original sources

Doxycycline versus tetracycline therapy for Lyme disease associated with erythema migrans.

BACKGROUND: Doxycycline is widely used to treat Lyme disease associated with erythema migrans. Whether it is comparable to tetracycline is unknown. OBJECTIVE: We conducted a two-part retrospective analysis of (1) the safety and efficacy of doxycycline compared with tetracycline and (2) the safety and efficacy of a 14-day versus a 20-day course of doxycycline. METHODS: Twenty-seven patients given tetracycline (500 mg four times a day for 14 days [group 1]) were compared retrospectively with 21 patients who received doxycycline (100 mg two or three times a day for 14 days [group 2]). The results for group 2 were also compared with that of 38 patients who received doxycycline for 20 days (100 mg three times daily) in a prospective treatment trial (group 3). RESULTS: There was no significant difference in the incidence of adverse drug effects or in efficacy at 1 month, but at 1 year there was a trend toward a better outcome in the group treated with tetracycline (p = 0.08). A 14-day course of doxycycline was comparable to a 20-day course in the incidence of adverse drug effects and in clinical outcome. CONCLUSION: The principal advantage of doxycycline over tetracycline for the treatment of Lyme disease associated with erythema migrans is the convenience of less frequent dosing, not enhanced efficacy or safety. There appears to be no advantage in extending treatment with doxycycline from 14 to 20 days.

Administration, Oral↗

Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans.

A randomized, multicenter, investigator-blinded clinical trial was undertaken in order to compare the efficacies of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. A total of 232 patients with physician-documented erythema migrans were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (119 patients), or doxycycline, 100 mg three times daily (113 patients), and clinical evaluations were conducted during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months posttreatment. Patients were assessed as to the resolution of erythema migrans and of the signs and symptoms related to early Lyme disease as well as to the prevention of late Lyme disease. A satisfactory clinical outcome (success or improvement) was achieved in 90 of 100 (90%) evaluable patients treated with cefuroxime axetil and in 89 of 94 (95%) patients treated with doxycycline (difference, -5%; 95% confidence interval, -12 to 3%). Patients with paresthesia, arthralgia, or irritability at enrollment were at higher risk for an unsatisfactory clinical outcome at 1 month posttreatment. Of the patients with satisfactory outcomes at 1 month posttreatment who were evaluable at 1 year posttreatment, a satisfactory outcome was achieved in 62 of 65 (95%) and in 53 of 53 (100%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -5%; 95% confidence interval, -10 to 4%). Twenty-eight percent of patients treated with doxycycline and 17% of those treated with cefuroxime axetil had one or more drug-related adverse events (P = 0.041). Doxycycline was associated with more photosensitivity reactions (6% compared with 0% for patients treated with cefuroxime axetil; P=0.006), and cefuroxime axetil was associated with more cases of diarrhea (5% compared with 0% for patients treated with doxycycline; P=0.030). Jarisch-Herxheimer reactions occurred in 12% of the patients in each treatment group. In summary, cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treatment of early Lyme disease and in preventing the subsequent development of late Lyme disease.

Adult↗

Sustained cellular immune responses to Borrelia burgdorferi: lack of correlation with clinical presentation and serology.

Fifty-one patients with erythema migrans were followed up prospectively with serial clinical evaluations, serologic determinations for antiborrelial antibodies, and lymphocyte stimulation responses to Borrelia burgdorferi antigens to determine (i) the factors associated with sustained cellular immune responses and (ii) whether lymphocyte stimulation is a good indicator of prior exposure to B. burgdorferi in patients treated early after erythema migrans. Positive lymphocyte stimulation responses ( > 2 standard deviations above normal control values) were found in 15 (29%) of 51 patients 3 months after treatment for erythema migrans and in 8 (18%) of 44 patients 1 year posttreatment. Heightened lymphocyte responses were not associated with the number or duration of erythema migrans lesions prior to treatment, the mean size of the largest erythema migrans lesion, or the number of symptoms at the time of presentation. The development of Jarisch-Herxheimer reaction, choice of antibiotic, and clinical outcome also were not associated with a positive lymphoproliferation assay result. Changes in the lymphocyte stimulation indices between the two time points assessed (3 months and 1 year posttreatment) also did not correlate with the above variables. When serologic results and lymphoproliferative responses were evaluated as categorical or continuous variables, there were no correlations between values. One year after treatment for early Lyme disease, lymphocyte reactivity is not a good indicator of prior infection with B. burgdorferi.

Adult↗

Comparison of different strains of Borrelia burgdorferi sensu lato used as antigens in enzyme-linked immunosorbent assays.

Eight strains of Borrelia burgdorferi sensu lato were tested with serum samples from persons who had Lyme borreliosis or syphilis in class-specific enzyme-linked immunosorbent assays (ELISAs). Antigens of B. burgdorferi sensu stricto, of Borrelia garinii, and of Borrelia spirochetes in group VS461 were prepared from cultured bacteria isolated from ticks, a white-footed mouse (Peromyscus leucopus), or human tissues in North America, the former Soviet Union, and Japan. Nearly all of the serum specimens that contained immunoglobulins to strain 2591, a Connecticut isolate, were also positive in antibody tests with the other seven strains. In general, all eight strains reacted similarly and were suitable as coating antigens in class-specific ELISAs. Assay sensitivities ranged from 82.6 to 100% in analyses for immunoglobulin M and G antibodies. Compared with reference antigen strain 2591, strains 231 (a tick isolate from Canada) and NCH-1 (a human skin isolate from Wisconsin) resulted in higher antibody titers in an ELISA. Syphilitic sera cross-reacted in all tests regardless of the antigen used. Key immunodominant proteins are shared among the closely related strains of B. burgdorferi sensu lato tested, but it is suspected that variations in antigen compositions among these spirochetes may sometimes affect assay performance for detecting serum antibodies.

Animals↗

Failure to isolate Borrelia burgdorferi after antimicrobial therapy in culture-documented Lyme borreliosis associated with erythema migrans: report of a prospective study.

BACKGROUND: Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, has occasionally been isolated from tissues or body fluids of patients after antimicrobial treatment. A prospective study of patients with Lyme borreliosis associated with erythema migrans (EM) was initiated in Westchester County, New York, to determine: (1) the clinical and laboratory parameters associated with culture positivity, and (2) the microbiologic response to treatment. METHODS: Skin biopsies were performed in patients with EM and cultured for B. burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. Subsequent biopsies for culture were performed adjacent to the original biopsy site for culture-positive patients after the completion of antimicrobial therapy. RESULTS: Initial biopsy cultures were performed for 44 patients; 6 were unevaluable due to culture contamination with other bacteria. Cultures were positive in 21 of 29 patients prior to treatment (72%), but in none of 9 patients during treatment (p < 0.001). The only other identified factor associated with successful recovery of B. burgdorferi was shorter duration of EM. When patients who had received prior antimicrobial therapy were excluded, the mean duration of the EM lesion for those with positive cultures was 5.0 +/- 5.2 days compared with 14.6 +/- 9.9 days for those with negative cultures (p < 0.01). B. burgdorferi could not be reisolated from any of 18 evaluable subsequent biopsies of skin from 13 culture-positive patients 4 to 209 days after completion of a course of antimicrobial therapy. Five patients had negative subsequent biopsy cultures on two separate occasions 3 to 5 months apart. CONCLUSIONS: After brief courses of antibiotics, B. burgdorferi appears to be rapidly eliminated from the skin at EM sites. The ability to recover B. burgdorferi from skin biopsy cultures of untreated patients with EM lesions wanes with increasing duration of EM, suggesting that this organism may also be spontaneously cleared from skin over time.

Adult↗

Entomologic and demographic correlates of anti-tick saliva antibody in a prospective study of tick bite subjects in Westchester County, New York.

We measured anti-tick saliva antibody (ATSA) by enzyme-linked immunosorbent assay using whole sonicated Ixodes dammini salivary glands as antigen in subjects with 1) a recent and confirmed I. dammini (n = 100) or Dermacentor variabilis bite (n = 3), 2) erythema migrans (n = 15), 3) late-stage Lyme disease (n = 4), and 4) normal controls without a history of tick bites (n = 5). Tick bite subjects had three ATSA determinations over approximately six weeks. On the first ATSA measurement at a mean +/- SD of 18.5 +/- 19.8 hr after removal of the tick, the subjects bitten by I. dammini had a mean ATSA optical density value (95% confidence interval [CI]) of 0.264 (0.223, 0.305); the corresponding value in controls was 0.142 (0.115, 0.169). There was no consistent change in ATSA levels in individuals with time. Multiple linear regression indicated that tick engorgement (P < 0.01), subject age (higher ATSA with increasing age; P = 0.01), and subject sex (females > males; P = 0.03) were all independent predictors of ATSA levels. Logistic regression revealed that a bite by I. dammini that became engorged (defined as an engorgement index > or = 3.4) was a risk factor for ATSA seropositivity (odds ratio [95% CI] = 6.2 [1.7, 21.8]). Finally, the ATSA test had a sensitivity of 0.81 and a specificity of 0.56 for a bite by I. dammini that became engorged. Overall, the data are further evidence that ATSA is a biologic marker of tick exposure, in that the engorgement index, a surrogate for tick saliva dose, was the strongest independent predictor of antibody response.

Adolescent↗

Use of a novel technique of cutaneous lavage for diagnosis of Lyme disease associated with erythema migrans.

OBJECTIVE: Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture Borrelia burgdorferi from the skin of suspected erythema migrans lesions. DESIGN: The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. SETTING: A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. PATIENTS: Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. INTERVENTION: Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. MAIN OUTCOME MEASURES: Growth of B burgdorferi in in vitro culture. RESULTS: Lavage fluid cultures grew B burgdorferi in 13 (29%) of the 45 cases (95% confidence interval [CI], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (P less than .09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (P less than .05, 12/30 vs 20/27). CONCLUSION: Cutaneous lavage is a new diagnostic technique for recovery of B burgdorferi from erythema migrans lesions that has potential applicability to other types of cutaneous infections.

Biopsy↗

Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease.

OBJECTIVE: To compare the efficacy of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. DESIGN: Randomized, multicenter, investigator-blinded clinical trial with clinical evaluations during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months post-treatment. SETTING: Three university referral centers and one private practice. PATIENTS: A total of 123 patients with physician-documented erythema migrans. INTERVENTION: Patients were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (63 patients), or doxycycline, 100 mg three times daily (60 patients). MEASUREMENTS: Resolution of erythema migrans and of signs and symptoms related to early Lyme disease as well as prevention of late Lyme disease. RESULTS: A satisfactory clinical outcome (success or improvement) was achieved in 51 of 55 (93%) evaluable patients treated with cefuroxime axetil and in 45 of 51 (88%) patients treated with doxycycline (difference, 5%, 95% Cl, -5% to 14%). The only complication at 1 month post-treatment was Lyme arthritis in one patient who received doxycycline. Of the patients with satisfactory outcomes at 1 month post-treatment who were evaluable at 1 year post-treatment, a satisfactory outcome was achieved in 43 of 48 (90%) and in 35 of 38 (92%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -2%; Cl, -12% to 7%). Lyme arthritis did not develop in any patient after 1 month post-treatment, whereas peripheral neuropathy was suspected in one patient treated with cefuroxime axetil. Thirty percent of patients treated with cefuroxime axetil and 32% of those treated with doxycycline had one or more drug-related adverse events. Doxycycline was associated with more photo-sensitivity reactions (15% compared with 0%; P = 0.001) and cefuroxime axetil with more diarrhea (21% compared with 7%; P = 0.035) and Jarisch-Herxheimer reactions (29% compared with 8%; P = 0.005). CONCLUSIONS: Cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treating of early Lyme disease and in preventing the subsequent development of late Lyme disease.

Adolescent↗

Prospective evaluation of heart block complicating early Lyme disease.

Lyme disease is a recognized cause of heart block/carditis. The incidence of heart block complicating early Lyme disease has not been prospectively evaluated. In this study, 61 patients with early Lyme disease documented by the rash of erythema migrans were prospectively evaluated for carditis. Fifty five of 61 patients had a repeat examination 3 to 4 weeks after initiation of antibiotic therapy. Only one of 61 patients (1.6%) presented with heart block, which resolved with antibiotics. None of the 54 patients without heart block on initial presentation had a change in any measured electrocardiographic parameter or progressed to heart block after antibiotics. Therefore, early Lyme disease appears to be infrequently complicated by heart block. Early administration of antibiotics may prevent the development of heart block/carditis.

Adult↗

Vesicular erythema migrans.

BACKGROUND: Lyme disease is the most common vector-borne disease in the United States. The characteristic rash, erythema migrans, is an early sign of the disease. Clinical criteria remain the "gold standard" for diagnosis at this stage of illness. OBSERVATIONS: Five (8%) of 65 patients with erythema migrans seen in a Lyme disease diagnostic center in Westchester County, New York, had a lesion with vesicles. Borrelia burgdorferi was cultured from two of five. In one case the positive culture came from a swab of the blister fluid. CONCLUSIONS: Recognition of erythema migrans and its variants is important, since early treatment of Lyme disease may prevent late complications. Vesicular erythema migrans should be added to the differential diagnosis of inflammatory vesicular rashes in the appropriate clinical setting.

Adolescent↗

Life-threatening complications of empiric ceftriaxone therapy for 'seronegative Lyme disease'.

Lyme disease, now the most common tick-borne illness in the United States, has recently received much media attention, due in part to its potentially serious sequelae in untreated patients. Because a rare patient with late illness may lack antibodies to the etiologic agent, Borrelia burgdorferi, physicians may be tempted to give empiric antibiotics for illnesses that may not be Lyme disease. We have described a patient who, despite negative laboratory evidence for late Lyme disease, was treated for 3 weeks with intravenous ceftriaxone and sustained serious complications, including granulocytopenia, fever, hepatitis, and Clostridium difficile-associated diarrhea. We caution physicians to weight carefully the risks of empiric treatment for ill-defined medical problems, and to recognize the hazards of even "safe" medications.

Adult↗

Otolaryngologic aspects of Lyme disease.

Lyme disease is a systemic illness caused by the spirochete Borrelia burgdorferi and transmitted by the bite of a tick in the Ixodes ricinus complex. While the illness is often associated with a characteristic rash, erythema migrans, patients may also present with a variety of complaints in the absence of the rash. The otolaryngologist may be called upon to see both groups of patients, with any number of signs and symptoms referable to the head and neck, including headache, neck pain, odynophagia, cranial nerve palsy, head and neck dysesthesia, otalgia, tinnitus, hearing loss, vertigo, temporomandibular pain, lymphadenopathy, and dysgeusia. We review our institutional experience with 266 patients with Lyme disease, 75% of whom experienced head and neck symptoms. We also summarize the diagnostic and treatment modalities for this illness.

Adolescent↗

Low-dose intermittent trimethoprim-sulfamethoxazole for prevention of Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection.

The important role of chemoprophylaxis for the prevention of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus type 1 (HIV)-infected patients is undisputed. The most cost-effective regimen, however, is unknown. We reviewed our experience at two hospitals in the New York City area in which low-dose, intermittent therapy with the combination of trimethoprim and sulfamethoxazole was used to prevent PCP in HIV-infected patients. During a total of 202 months of primary prophylaxis in 32 patients and 319 months of secondary prophylaxis in 35 patients, PCP was diagnosed only once. More than 80% of patients were receiving zidovudine concomitantly. Adverse reactions to trimethoprim-sulfamethoxazole occurred in 31% and 52% of those receiving primary or secondary prophylaxis, respectively. When those patients who were considered ineligible to receive trimethoprim-sulfamethoxazole prophylaxis (principally based on a prior adverse drug reaction) are also factored in, then approximately 50% of HIV-infected patients are candidates for long-term trimethoprim-sulfamethoxazole prophylaxis. The projected cost savings of this prophylaxis regimen, compared with those currently recommended by the US Public Health Service, are enormous.

Acquired Immunodeficiency Syndrome↗

Isolation of Borrelia burgdorferi from the blood of seven patients with Lyme disease.

PURPOSE: Borrelia burgdorferi, the etiologic agent of Lyme disease, has rarely been successfully cultured from blood. We report on seven patients from Westchester County, New York, with B. burgdorferi bacteremia diagnosed between April 1987 and August 1987. PATIENTS AND METHODS: One hundred thirty-two attempts to isolate spirochetes were made on blood specimens obtained from 104 patients. Twenty-two of these specimens were obtained from nine patients who had recently been bitten by Ixodes ticks but who were asymptomatic. Heparinized blood or serum specimens (0.2 to 0.4 mL) were inoculated onto 6 mL of modified Barbour-Stoenner-Kelly medium. Lyme serology was performed by enzyme-linked immunosorbent polyvalent, IgM, and IgG assays, fluorescent immunoassay, and microhemagglutination. RESULTS: Four of the seven patients had erythema migrans, two had facial nerve palsy, and one had a flu-like syndrome without rash. These patients represented 21% (four of 19) of all patients with the characteristic skin lesion who had blood cultures for B. burgdorferi, and 40% (two of five) of all those with facial nerve palsy. Serologic testing was frequently nonreactive; two patients had no detectable antibody on multiple sera by five different assays. All patients improved with antibiotic treatment, and had negative subsequent blood cultures, but five of seven had persistent complaints after completion of therapy. CONCLUSION: Culturing blood for B. burgdorferi may be useful in confirming the diagnosis of Lyme disease in selected patients. Use of spirochete blood cultures may facilitate a better understanding of the pathogenesis and natural history of Lyme disease.

Adolescent↗

Survival of Borrelia burgdorferi in human blood stored under blood banking conditions.

Hematogenous dissemination of organisms occurs in many spirochetal diseases, including Lyme disease and syphilis. Although syphilis has been transmitted by transfusion, in the vast majority of cases, only fresh blood products were involved, in part because Treponema pallidum survives poorly when refrigerated in citrated blood. Because of the rising incidence of Lyme disease in certain areas, whether its causative agent, Borrelia burgdorferi, could survive under blood banking conditions was studied. Dilutions of stock cultures of two strains of B. burgdorferi were inoculated into samples of citrated red cells (RBCs). Viable spirochetes were recovered from RBCs inoculated with 10(6) organisms per mL, after refrigeration for as long as 6 weeks. It is concluded that B. burgdorferi may survive storage under blood banking conditions and that transfusion-related Lyme disease is theoretically possible.

Blood Banks↗