Oral vs intravenous ciprofloxacin in the initial empirical management of severe pyelonephritis or complicated urinary tract infections: a prospective randomized clinical trial.

BACKGROUND: There are few data on the efficacy of oral antibiotics in the initial empirical management of severe forms of urinary tract infection (UTI). METHODS: In a multicenter, prospective, randomized trial we compared oral (500 mg twice daily) vs intravenous ciprofloxacin (200 mg twice daily) in the initial empirical management of hospitalized patients with serious forms of UTI. Exclusion criteria were severe sepsis, inability to take oral medication, or the presence of obstruction or renal foci of suppuration. The study population included 66 women with pyelonephritis, 43 patients with community-acquired UTIs, and 32 patients with hospital-acquired UTIs. The frequency of bacteremia was 28 (42%) of 66 in the patients with pyelonephritis and 25 (33%) of 75 in those with complicated UTIs. Seventy-two patients were randomized to treatment with oral and 69 to intravenous ciprofloxacin. RESULTS: There were no infection-related deaths and no patients required an early change of antibiotics because of worsening clinical status during the initial empirical phase of treatment. The mean duration of fever was 1.7 days in patients treated by the oral vs 1.9 days in patients treated by the intravenous route (P = .15). The rates of microbiological failure (3% in the oral vs 2% in the intravenous treatment group) and of unsatisfactory clinical response (4% oral vs 3% intravenous) were low. A treatment change was eventually required in 14% of the patients assigned to the oral and 7% of the patients assigned to the intravenous regimen, mainly because of the isolation of enterococci or ciprofloxacin-resistant organisms in pretherapy urine specimens. CONCLUSIONS: In the hospital setting, oral ciprofloxacin is as effective as the intravenous regimen in the initial empirical management of serious UTIs, including bacteremic forms, in patients without severe sepsis, obstruction, or renal foci of suppuration. The efficacy of the oral regimen indicates a potential use for ciprofloxacin in outpatient treatment of a subset of patients currently hospitalized on account of disease severity.

[Beta-lactam/beta-lactamase inhibitor combinations for oral administration]. / Beta-Laktam-beta-Laktamase-Inhibitor-Kombinationen für die orale Anwendung.

Beta-lactamase inhibitors are compounds which are able to bind many beta-lactamase and to inactivate them irreversibly ("suicide inactivators"). Their intrinsic antimicrobial activity is weak. However, in combination with aminopenicillins they exhibit marked synergism both in vitro and in vivo against many beta-lactamase producing bacterial strains. At the achievable serum and tissue concentrations after oral administration, various aminopenicillin/beta-lactamase inhibitor combinations are active against many strains of beta-lactamase producing Haemophilus influenzae, Moraxella catarrhalis, Bacteroides fragilis and staphylococci. At levels achievable in the urine, they are also active against many strains of Escherichia coli, Proteus spp. and Klebsiella spp. Clinically, they have been shown to be effective in the treatment of various human infections of the urinary tract, airways, skin, soft tissues, ear and sinuses. Mild gastrointestinal disturbances are the most commonly encountered side effects. Aminopenicillin/beta-lactamase inhibitor combinations may be a suitable therapeutic option in treating mild to moderately severe infections, i.e. in an outpatient setting.

Beta-lactam resistance mechanisms of methicillin-resistant Staphylococcus aureus.

In vitro and in vivo activity of amoxicillin and penicillin G alone or combined with a penicillinase inhibitor (clavulanate) were tested against five isogenic pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not producing penicillinase. Loss of the penicillinase plasmid caused an eight times or greater reduction in the MICs of amoxicillin and penicillin G (from greater than or equal to 64 to 8 micrograms/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (greater than or equal to 64 micrograms/ml). This difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin-binding protein 2a affinity of amoxicillin and penicillin G than of methicillin and a greater than or equal to 90% successful amoxicillin treatment of experimental endocarditis due to penicillinase-negative MRSA compared with cloxacillin, which was totally ineffective (P less than .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Penicillinase-sensitive beta-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infections.

[Iron and iron-binding proteins in the differential diagnosis of pleural effusion]. / Eisen und eisenbindende Proteine in der Differentialdiagnose von Pleuraergüssen.

Iron, iron-binding capacity, lactoferrin and total protein were determined in the plasma and pleural fluid of 30 patients with cardiac failure (n = 10), infectious/inflammatory disease (n = 9) and metastatic carcinoma (n = 11). In 16 patients pleural transferrin and ferritin was also measured. Plasma iron and total iron-binding capacity were reduced in inflammatory and neoplastic disease, whereas hyposideremia with normal iron-binding capacity was seen in patients with heart failure. Plasma lactoferrin was reduced in metastatic carcinoma. Exudates (protein greater than or equal to 30 g/l; infectious/inflammatory: 9/9, carcinomatous: 10/11) had significantly higher iron, lactoferrin, transferrin and ferritin concentrations than transudates (protein less than 30 g/l; heart failure: 10/10, carcinomatous: 1/11). Statistically, infectious/inflammatory exudates could be distinguished from neoplastic exudates by a higher median iron concentration (non-parametric Wilcoxon-Mann-Whitney test). Overlap of the respective ranges, however, did not allow a clear-cut differential diagnosis in individual cases. Pleural lactoferrin concentrations, on the other hand, correlated with the pleural granulocyte count and nonspecifically reflect the degree of granulocytic inflammation. Positive pleural/plasma correlations of protein and of iron concentrations were found in exudates only. Within exudates and transudates, on the other hand, total protein correlated with transferrin but not with iron concentrations. Therefore, and because of the substantially higher pleural/plasma ratio for iron than for transferrin concentrations, a quantitatively important, non-transferrin bound iron pool in pleural fluids, most probably ferritin, must be assumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Coagulation and fibrinolysis in acute mountain sickness and beginning pulmonary edema.

To examine whether intravascular coagulation and/or decreased fibrinolysis precedes high-altitude pulmonary edema (HAPE) we examined 25 male mountaineers (median age 40 yr) at low altitude (550 m) and after 6, 18, and 42 h at an altitude of 4,559 m, which was climbed in 24 h. In 14 subjects, 2 of whom showed radiological evidence of HAPE after 42 h, symptoms of acute mountain sickness (AMS) were mild or absent. Eleven subjects suffered from AMS, six of whom developed radiologically documented HAPE after 18 or 42 h. In the absence of AMS there were no significant changes at high altitude, with the exception of a decrease in bleeding time from 246 +/- 18 to 212 +/- 13 (SE) (P less than 0.05). In AMS, partial thromboplastine time decreased from 34.2 +/- 0.8 to 31.1 +/- 0.5 s (P less than 0.001) and factor VIII procoagulant activity and von Willebrand factor antigen were increased by 57 +/- 12 and 70 +/- 13%, respectively (P less than 0.001), whereas there were no significant changes in beta-thromboglobulin (BTG), fibrinopeptide A (FPA), and fibrin fragment B beta 15-42. In subjects with HAPE, BTG, FPA, and B beta 15-42 were normal before and in beginning HAPE. Preceding HAPE, euglobulin clot lysis time declined at high compared with low altitude from 289 +/- 48 to 201 +/- 42 min without venous occlusion (VO) and from 107 +/- 36 to 86 +/- 31 min after VO (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

High-altitude pulmonary edema: findings at high-altitude chest radiography and physical examination.

Twenty-five male volunteers underwent chest radiography at 550 m above sea level (baseline) and at 4,559 m at 6, 18, and 42 hours after arrival. Nine had a history of high-altitude pulmonary edema (HAPE). Starting by 6 hours and independent of the consecutive presence of HAPE, the diameters of the central pulmonary arteries increased by 10%-30% at 4,559 m. At 18 hours and, increasingly, at 42 hours, radiographic evidence of HAPE developed in eight subjects: six with previously documented HAPE and two without. Radiographic signs of HAPE were most severe peripherally, and morphologic characteristics were compatible with permeability and/or overperfusion edema and normal pulmonary venous pressure. Extensive radiographic findings were accompanied by discrete pulmonary rales, and chest radiography proved valuable in detecting HAPE in subjects with normal findings of lung auscultation. This study demonstrates a significant individual susceptibility of lowland residents with a history of HAPE to develop HAPE, resulting in a recurrence rate of 66%.

Atrial natriuretic peptide in acute mountain sickness.

To test the hypothesis that elevated atrial natriuretic peptide (ANP) may be involved in altered fluid homeostasis at high altitude, we examined 25 mountaineers at an altitude of 550 m and 6, 18, and 42 h after arrival at an altitude of 4,559 m, which was climbed in 24 h starting from 3,220 m. In 14 subjects, symptoms of acute mountain sickness (AMS) were absent or mild (group A), whereas 11 subjects had severe AMS (group B). Fluid intake was similar in both groups. In group B, urine flow decreased from 61 +/- 8 (base line) to 36 +/- 3 (SE) ml/h (maximal decrease) (P less than 0.05) and sodium excretion from 7.9 +/- 0.9 to 4.6 +/- 0.7) mmol.l-1.h-1 (P less than 0.05); ANP increased from 31 +/- 4 to 87 +/- 26 pmol/l (P less than 0.001), plasma aldosterone from 191 +/- 27 to 283 +/- 55 pmol/l (P less than 0.01 compared with group A), and antidiuretic hormone (ADH) from 1.0 +/- 0.1 to 2.9 +/- 1.2 pmol/l (P = 0.08 compared with group A). These variables did not change significantly in group A, with the exception of a decrease in plasma aldosterone from 189 +/- 19 to 111 +/- 17 pmol/l (P less than 0.01). There were no measurable effects of elevated ANP on natriuresis, cortisol, or blood pressure. The reduced diuresis in AMS may be explained by increased plasma aldosterone and ADH overriding the expected renal action of ANP. The significance of elevated ANP in AMS remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS)