Bo Settergren

Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial

BACKGROUNDnAcute pyelonephritis is a common infection in adult women, but there is a paucity of controlled trials of its treatment and the optimum duration of antibiotic treatment has not been properly defined. We compared the efficacy of ciprofloxacin for 7 days and 14 days in women with community-acquired acute pyelonephritis.nnnMETHODSnIn a prospective, non-inferiority trial undertaken at 21 centres of infectious diseases in Sweden, women (aged ≥18 years) who were not pregnant and had a presumptive diagnosis of acute pyelonephritis were randomly assigned to oral treatment with ciprofloxacin 500 mg twice daily for 7 days or 14 days. The first week was open label. A computer-generated randomisation list in block sizes of two was used for treatment allocation in a 1:1 ratio. The study was double-blind and placebo-controlled during the second week of treatment, which was either continuation of ciprofloxacin 500 mg or placebo tablets twice daily according to the randomisation code. Patients, carers, site investigators, and trial coordinating centre staff were masked to group assignment. The primary endpoint was the clinical and bacteriological outcome 10-14 days after completion of treatment with active drug. Analysis was by per protocol. This trial is registered with EudraCT, number 2005-004992-39, and ClinicalTrials.gov, number ISRCTN73338924.nnnFINDINGSn126 of 248 patients were randomly assigned to 7 days and 122 to 14 days of ciprofloxacin. 73 and 83 patients, respectively, were analysed. Short-term clinical cure occurred in 71 (97%) patients treated with ciprofloxacin for 7 days and 80 (96%) treated for 14 days (difference -0·9%; 90% CI -6·5 to 4·8; p=0·004; non-inferiority test). Cumulative efficacy at long-term follow-up was 93% in each group (68 of 73 vs 78 of 84; -0·3%; -7·4 to 7·2; p=0·015). Both regimens were well tolerated. Two patients discontinued ciprofloxacin because of myalgia with 7 days of treatment and itching exanthema with 14 days. Four (5%) of 86 patients assigned to 7 days of treatment who complied with study criteria and six (6%) of 93 assigned to 14 days reported an adverse event after the first week of treatment that was possibly or probably related to the study drug. In those assigned to 7 days, no patient had mucosal candida infection after the first week versus five treated for 14 days (p=0·036).nnnINTERPRETATIONnOur results show that acute pyelonephritis in women, including older women and those with a more severe infection, can be treated successfully and safely with oral ciprofloxacin for 7 days. Short courses of antibiotics should be favoured in an era of increasing resistance.nnnFUNDINGnSwedish Strategic Programme against Antibiotic Resistance (Strama).

Prevalence of serum IgG antibodies to Puumala virus (haemorrhagic fever with renal syndrome) in northern Sweden.

A stratified and randomly-selected population sample was identified in 1990 in order to study the seroprevalence of nephropathia epidemica (haemorrhagic fever with renal syndrome) in Northern Sweden. Sera from 1538 subjects (750 men, 788 women), 25-64 years of age, were analysed for the presence of Puumala virus (PUV) specific-IgG by the indirect immunofluorescence antibody test. Specific IgG was detected in sera from 83 subjects (5.4%). Men and women had similar seroprevalence rates. The highest seroprevalences were found in subjects 55 years or older (8.0%) and among farmers and forestry workers (15.9%). The geographic distribution of seropositive individuals was uneven and there were significantly more seropositive persons in rural than in urban areas (P < 0.05).

Pulmonary involvement in nephropathia epidemica as demonstrated by computed tomography

SummaryIn a prospective study 19 adult patients with nephropathia epidemica were examined in the acute phase of disease with computed tomography (CT) of the lungs and conventional chest radiography. Infiltrates and/or pleural effusions were seen in ten of 19 patients. In two of the patients, abnormalities were disclosed only by CT. Patients with pathologic radiography findings had a more pronounced inflammatory response, as measured by C-reactive protein and leukocyte count, than did those with normal radiography findings. It is concluded that radiological evidence of pulmonary involvement is a common finding early in the course of nephropathia epidemica. The possibility that the lung may be a site of viral replication merits further investigation.ZusammenfassungNeunzehn erwachsene Patienten in der akuten Phase von Nephropathia epidemica wurden mit computertomographischem (CT) und konventionellem Thoraxröntgen untersucht. Infiltrate und/oder Pleuraergüsse wurden bei 10/19 der Patienten beobachtet. Bei zwei Patienten konnten pathologische Befunde nur mit Hilfe der CT erhoben werden. Patienten mit pathologischen Radiogrammen wiesen, verglichen mit normalen radiographischen Befunden, eine ausgeprägtere Entzündungsreaktion gemessen durch C-reaktives Protein und Leukozytenzahlen auf. Unsere Resultate zeigen, daß in der Frühphase der Nephropathia epidemica röntgenologisch häufig eine Lungenbeteiligung nachgewiesen werden kann. Die Möglichkeit, der Lunge als eine Lokalisation der viralen Replikation sollte weiter untersucht werden.In a prospective study 19 adult patients with nephropathia epidemica were examined in the acute phase of disease with computed tomography (CT) of the lungs and conventional chest radiography. Infiltrates and/or pleural effusions were seen in ten of 19 patients. In two of the patients, abnormalities were disclosed only by CT. Patients with pathologic radiography findings had a more pronounced inflammatory response, as measured by C-reactive protein and leukocyte count, than did those with normal radiography findings. It is concluded that radiological evidence of pulmonary involvement is a common finding early in the course of nephropathia epidemica. The possibility that the lung may be a site of viral replication merits further investigation. Neunzehn erwachsene Patienten in der akuten Phase von Nephropathia epidemica wurden mit computertomographischem (CT) und konventionellem Thoraxröntgen untersucht. Infiltrate und/oder Pleuraergüsse wurden bei 10/19 der Patienten beobachtet. Bei zwei Patienten konnten pathologische Befunde nur mit Hilfe der CT erhoben werden. Patienten mit pathologischen Radiogrammen wiesen, verglichen mit normalen radiographischen Befunden, eine ausgeprägtere Entzündungsreaktion gemessen durch C-reaktives Protein und Leukozytenzahlen auf. Unsere Resultate zeigen, daß in der Frühphase der Nephropathia epidemica röntgenologisch häufig eine Lungenbeteiligung nachgewiesen werden kann. Die Möglichkeit, der Lunge als eine Lokalisation der viralen Replikation sollte weiter untersucht werden.

A swedish fatal case of nephropathia epidemica

A previously healthy 55-year-old man with nephropathia epidemica (NE) developed disseminated intravascular coagulation, anuria and shock and died on day 6 of his disease. By use of indirect immunofluorescence technique and ELISA, specific serum IgM antibodies against Puumala virus could be detected, thus confirming the clinical diagnosis. This case demonstrates that NE in Scandinavia is a potentially lethal disease.

Hemorrhagic fever with renal syndrome : comparison of clinical course in Sweden and in the Western Soviet Union

The severity of the clinical course in 355 Swedish and 603 Soviet patients with serologically confirmed hemorrhagic fever with renal syndrome (HFRS) was compared retrospectively. The overall frequency of hemorrhagic manifestations including also benign bleeding such as ecchymoses was higher among Soviet than among Swedish patients (37% vs. 10%). However, severe hemorrhagic complications (gastrointestinal and renal tract bleeding) were equally common in both countries. There were 2 fatal Soviet cases, whereas none of the Swedish patients died. We conclude that the clinical presentation of HFRS in Sweden and in the Western Soviet Union shows many similarities but there seems to be a higher frequency of life threatening complications among the patients in the Western USSR.

Specific serum IgA, IgG and IgM antibody determination by a modified indirect ELISA-technique in primary and recurrent herpes simplex virus infection

Twenty-three patients with a herpetic infection as diagnosed by a positive culture of herpes simplex virus (HSV) were studied with respect to serological responses of IgA, IgG and IgM antibodies in paired serum samples by an indirect (sandwich) enzyme linked immunosorbent assay (ELISA). Eight of the patients had a primary infection and 15 a recurrent one. In the ELISA test a detergent treated cell lysate of HSV type 1 was used as antigen. In the IgM assay all sera were pretreated with antihuman IgG with the purpose to precipitate IgG of the samples. The conjugate was a F(ab)2-fragment of antihuman-IgM. In primary infections all patients had significant titre rises of IgG and presence of high IgM titres in the convalescent serum. IgA antibodies were found in all of them, while titre rises were detected in 5/8. In recurrent infections titre rises of IgG and IgA antibodies were found in 4 and 5, respectively. Six had detectable IgM in one or both of the paired samples. The IgG titres were higher in recurrent infections than in primary, in contrast to IgM of which much higher titres were found in primary infections. It is concluded that in primary infections a conclusive serological diagnosis was established in all patients, whereas in recurrent infections this was achieved in two of three patients. The indirect ELISA method used for IgM detection was sensitive, reliable and convenient. Interfering rheumatoid factor was effectively eliminated by treatment with antihuman IgG.

Nephropathia epidemica (hemorrhagic fever with renal syndrome) in children: clinical characteristics

The clinical characteristics of serologically verified nephropathia epidemica, the Scandinavian form of hemorrhagic fever with renal syndrome, were studied in Swedish children who were < 15 years of age. In 1990 to 1992, 14 cases were prospectively followed. A retrospective survey during 1984 to 1990 disclosed another 18 cases. Among the 32 cases (20 boys, 12 girls, 3 to 15 years of age; median age, 11 years), the most common symptoms were fever (100%), headache (100%), abdominal pain (93%), vomiting (91%) and back pain (76%). Laboratory findings included elevated serum creatinine concentration (19 of 28) and thrombocytopenia (7 of 22). Urinalysis showed proteinuria (31 of 31 patients) and hematuria (24 of 30). Six children had mild hemorrhagic manifestations (epistaxis, metrorrhagia, and petechiae). No severe complications occurred. The clinical symptoms of children with nephropathia epidemica seem to be similar to those found among adult nephropathia epidemica cases.

A Case of Haemorrhagic Fever with Renal Syndrome Complicated by Spleen Haemorrhage

A case of haemorrhagic fever with renal syndrome (HFRS) complicated by spleen haemorrhage is described. The patient developed progressive anaemia, hypotension and signs of preshock. Computerized tomography demonstrated extensive haematoma in the spleen and splenectomy was performed. This case confirms previous reports that HFRS caused by Puumala virus may be associated with severe haemorrhagic manifestations.

Laboratory findings in patients with hemorrhagic fever with renal syndrome in western Russia.

Hemorrhagic fevers with renal syndrome (HFRS) comprise a group of closely related diseases caused by different hantaviruses [1]. HFRS in Western Russia is most often caused by Puumula virus serotypes [2]. The major clinical features of HFRS in Russia have previously been well documented [3-7]. However, to our knowledge there are no reports in the English literature on laboratory findings of Russian HFRS patients. The aim of the present study was to document laboratory findings mainly reflecting renal involvement, coagulation and acute phase responses. One hundred seventy-eight adult Russian HFRS patients (158 men, 20 women , mean age 38 years; range 15-63 years) admitted to the Department of Infectious Diseases, Clinics of Medical Institute, Samara, Russia, were included in a prospective study dming 1988-89. Samara is located in a highly endemic HFRS region; > 600 cases were hospitalised in 1987-90. The median day of hospitalisation was 5 (range 3-11) days after onset of disease. Acute-and convalescent phase sera from each patient were examined by an indirect immunofluorescence antibody technique [2] using Puumula virus as antigen. Patients with a 4-fold or greater increase in titer of IgG antibody to Puumula virus were accepted as serologically verified cases. Blood and urine samples were collected at least twice from each patient. Serum or plasma levels of creatinine, urea nitrogen, fibrinogen and prothrombin as well as the number of platelets and leucocytes were measured by standard routine laboratory methods. Serum and urinary [32-microglobulin levels were determined by radioimmunoassay (Pharmacia Diagnostics AB, Uppsala, Sweden). Commercially available dip slide tests were used for estimating proteinuria, hematuria and glucosuria. Table 1 gives the results of the blood chemistry and urinary findings. In total, 162 patients had proteinuria; 13 (8%) of them excreted > 6.6 g of protein/1 in the urine. Severely decreased glomerular filtration rate as indicated by serum creatinine concentrations above 500 gmol/1 were documented in 31 (17%) of the patients. No patient died and none required dialysis. The pathogenesis of HFRS has not been elucidated in detail, but several observations support a central role for immune mechanisms [8], including activation of both cell mediated and humoral responses. In the present study a majority of patients showed an inflammatory response as indicated by aLaboratory findings in patients with hemorrhagic fever with renal syndrome in western Russia.

Long-term persistence of false positive antibody reactivity in HIV western blot testing of sera from a healthy blood donor.

HIV-Western blot (WB) testing of sequential sera from a blood donor revealed identical bands in the p24 and p55 positions. Additional testing using indirect immunofluorescence antibody technique, radioimmunoprecipitation assay and an HIV p24 antigen immunoassay were negative. During a 5-year follow-up period the blood donor has remained apparently healthy and no signs of disease have developed. We conclude that sera from this blood donor show a false positive HIV WB reactivity. The nature of this reactivity remains obscure but has practical implications for the routine HIV screening of blood donors.