Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis.

To compare the efficacy of oral doxycycline and IV penicillin G for the treatment of neuroborreliosis, we randomized consecutive patients with Lyme neuroborreliosis to receive either IV penicillin G (3 g q 6 h) or oral deoxycycline (200 mg q 24 h) for 14 days. All patients had antibodies against Borrelia burgdorferi in serum, CSF, or both, or had a positive CSF culture. Twenty-three patients randomized to penicillin G and 31 patients to doxycycline were included in the study. All patients improved during treatment, and there were no significant differences between the two treatment groups in patient scoring, CSF analysis, or serologic and clinical follow-up during 1 year. There were no treatment failures, although one patient in each treatment group was re-treated because of residual symptoms. In conclusion, oral doxycycline is an adequate and cost-effective alternative to IV penicillin for the treatment of Lyme neuroborreliosis.

Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women.

The pharmacokinetics of cephradine, a cephalosporin with a low degree of protein binding, was studied in 12 women after oral and intravenous administration of the drug during and after pregnancy. Six of the 12 women also received a cephalosporin with a high degree of protein binding, cefazolin, intravenously during and after pregnancy. For both drugs most pharmacokinetic parameters were altered in pregnancy. The area under the plasma concentration-time curve (AUC) following intravenous administration was smaller for both drugs during as compared to after pregnancy (mean change 39% for cephradine and 31% for cefazolin). Half-lives of both drugs were significantly shorter during compared with after pregnancy (mean change 26% for cephradine and 35% for cefazolin). Consequently, total body clearance was increased during pregnancy. A significant negative correlation between length of gestation and total clearance per kg bodyweight was seen for cephradine. The bioavailability of oral cephradine did not differ significantly during compared with after pregnancy. It is concluded that the dosage of both cefazolin and cephradine should be increased when treating infections in pregnant women in order to obtain the same antibacterial effect as when treating non-pregnant women.

Clinical manifestations and diagnosis of neuroborreliosis.

Lyme borreliosis has in a few years turned out to be a health problem not only in the United States, but also in many European countries. When it affects the nervous system, Lyme borreliosis acts as the great disease imitator. Because of this characteristic it is often difficult to diagnose on clinical grounds. Patients with neuroborreliosis might appear within all medical disciplines. Clinical markers, such as preceding tick bite and/or ECM, are important clues to the diagnosis. Mononuclear pleocytosis and elevated CSF protein are present in most patients with neuroborreliosis. Final evidence for the diagnosis is the demonstration of specific antibodies in serum and/or CSF. Measurement of antibody titers should be carried out in both serum and CSF, since these methods are complementary when trying to obtain a serological diagnosis of neuroborreliosis.

Treatment of Lyme borreliosis with emphasis on neurological disease.

We have studied 113 patients with neurologic Lyme borreliosis and meningitis who were treated with intravenous high-dose antibiotics (penicillin G, 12 g, mostly for 14 days in 47 patients; penicillin G, 9 g, mostly for 10 days in 58 patients; doxycycline, 200 mg, in 5 patients; and cefuroxime, 4.5-9 g, in 3 patients). Seventy percent of the patients had peripheral nerve symptoms and 13% had central nervous symptoms. Almost half of the patients were treated more than 4 weeks after the onset of symptoms and 15% of the patients had persisting or progressive symptoms between 4 and 11 months. There seemed to be clinical benefit as well as a decrease of spinal fluid pleocytosis and spinal proteins. No significant symptoms of Herxheimer reaction were demonstrated.

Long-term persistence of intrathecal virus-specific antibody responses after herpes simplex virus encephalitis.

Paired sera and cerebrospinal fluids (CSF) from nine surviving patients were collected 4.5 to 8 years after acute herpes simplex (HS) virus encephalitis. Oligoclonal bands of IgG were detected in the CSF of all, and seven patients had an elevated CSF IgG index. Antibodies to HS, varicella-zoster (VZ), measles, and cytomegalo viruses were analysed by enzyme-linked immunosorbent assay (ELISA) and by imprint immunofixation (IIF) of specimens separated by electrophoresis and by thin-layer electrofocusing. Intrathecal synthesis of HS and VZ IgG antibodies was demonstrated in all and of measles IgG antibodies in one patient by both methods. Intrathecal synthesis of HS IgA antibodies was demonstrated by ELISA in three and by IIF in seven patients; the latter method also disclosed intrathecal synthesis of VZ IgA antibodies in two. No patient had intrathecal synthesis of viral IgM antibodies. The intrathecally synthesized antibodies demonstrated by IIF displayed oligoclonal characteristics. The IIF analyses as well as virus absorption tests indicated that the intrathecally synthesized VZ IgG and IgA antibodies could be explained as HS antibodies cross-reacting with VZV. The results indicate that a long-term persistence of intrathecal antibody responses to HS virus is a common feature after acute HS encephalitis. The intrathecal production of measles IgG antibodies in one case may reflect a similar persistence of non-specific immune responses induced during the acute infection.

Tick-borne Borrelia infection in patients with Bell's palsy.

An enzyme-linked immunosorbent assay was applied to serum samples of 94 patients diagnosed as having Bell's palsy: they were studied throughout two consecutive years in an attempt to establish serologic evidence of a tick-borne spirochetal infection. A strain of Borrelia spirochetes, isolated from Swedish Ixodes ricinus ticks, was used as an antigen, and separate estimations of spirochetal IgG and IgM antibodies were made; serum samples with titers above the 95th-percentile level of 120 healthy individuals were considered positive. Thirteen percent of the patients' serum samples were IgG-positive, 3% were positive for IgM, and 3% were positive for both IgG and IgM. A twofold or greater increase of IgG titers was found in 6%. All the patients who were seropositive experienced the onset of palsy during the period from July to December.

Trimethoprim-sulfamethoxazole plus amikacin as first-line therapy and imipenem/cilastatin as second empirical therapy in febrile neutropenic patients with hematological disorders.

One hundred and thirty-nine consecutive episodes of fever were evaluated in 55 patients with hematological disorders during persistent neutropenia. In 121 instances, patients were given trimethoprim-sulfamethoxazole + amikacin (TMP/SMZ + AMI) as an initial antibiotic regimen with clinical success in 51% (i.e. antibiotic treatment was not changed within the first 7 days). Imipenem/cilastatin (I/C) therapy was instituted in: (a) 22 episodes with clinical failure and fever of unknown origin during TMP/SMZ + AMI therapy and (b) 18 episodes with a second fever episode during initially successful TMP/SMZ + AMI therapy. The response rate for all 40 I/C treated episodes was 80%. One neutropenic patient in the whole series died from infectious complications within four weeks from institution of therapy. TMP/SMZ+AMI seems to be a safe and inexpensive "standard" antibiotic regimen in neutropenic patients. I/C appears to have good efficacy when used as secondary therapy after failure with TMP/SMZ+AMI.

Imipenem/cilastatin monotherapy as salvage treatment in febrile neutropenic patients.

Imipenem/cilastatin (I/C) monotherapy was used as salvage treatment in 55 neutropenic patients (58 fever episodes) after treatment failure on first-line antibiotic therapy. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiologic evidence of infection on I/C monotherapy alone. Twenty-five out of the 58 episodes (43%) were classified as success, 6 episodes (10%) as initial response but the regimen had to be modified (amphotericin B was added) and 27 episodes (47%) as failures. In episodes with documented infections 9 out of 23 (39%) were classified as success. All patients survived during the first 72 hours after change to I/C therapy. One patient had to discontinue I/C due to a skin rash. In conclusion, the use of a treatment algorithm with I/C monotherapy as second-line treatment was safe and effective. Other antimicrobial agents, most often vancomycin and/or amphotericin B, had to be added in half of the patients.

Serum and cerebrospinal fluid examinations in the diagnosis of Borrelia infection in Bell's palsy.

Seventy-two consecutive patients with Bell's palsy were investigated for evidence of tick-borne Borrelia infection and to compare the merits of serum and cerebrospinal fluid examinations in the diagnosis of Borrelia infection. Serum was taken in the acute and convalescent stages from 72 patients, and cerebrospinal fluid was obtained from 35 of these. An enzyme-linked immunosorbent assay (ELISA) was used to analyse serum and cerebrospinal fluid samples for IgG and IgM antibodies against the Borrelia spirochete. The serum of 8 (11%) of the 72 patients was positive for IgG or both for IgG and IgM. Only 1 of the 35 patients presented an elevated titre of IgG and IgM in the cerebrospinal fluid as well as elevated IgG and IgM titres in the serum. The results, even if limited, indicate that screening of serum is sufficient to exclude Borrelia infection in cases of uncomplicated isolated acute peripheral facial palsy.