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Ciprofloxacin was studiedin vitro and in an experimental thigh infection model in mice to evaluate its efficacy againstPseudomonas aeruginosa in comparison with that of tobramycin. Thein vivo experiments were carried out in normal mice as well as mice rendered granulocytopenic by irradiation. The MIC of ciprofloxacin for two Pseudomonas strains was 0.125 mg/l and 0.25 mg/l and that of tobramycin 0.25 mg/l and 4.0 mg/l, respectively.In vitro short-term growth experiments revealed that as far as initial killing rate is concerned, ciprofloxacin was 2.20 times as potent as tobramycin against the first strain and 45.4 times as potent against the second strain. Thein vivo experiments were performed by injecting the micro-organism into the thigh muscle and counting colony forming units (CFUs) after several hours of exposure to the antibiotics. The results for irradiated mice indicate that ciprofloxacin was 2.0 times as potent as tobramycin against the first strain and 37.8 times as potent against the second strain, when related to dosage. For normal mice these values were 2.0 and 16.0, respectively, which is more than would be expected from thein vitro experiments because the mean plasma concentrations of tobramycin were about four times higher than those of ciprofloxacin.

Serially collected serum samples from 81 patients with acute non-A, non-B hepatitis were tested for the presence of antibodies to hepatitis C virus (anti-HCV) by a second-generation enzyme immunoassay (EIA) test. Anti-HCV was detected in 56 cases (69%) during the first month, in 61 cases (75%) at 3 months and in 63 cases (78%) at 6 months. In those 18 patients showing anti-HCV negative results in the three determinations, hepatitis C virus (HCV) RNA was tested using a nested polymerase chain reaction (PCR) in the first serum sample and was detected in only one case. Anti-HCV or HCV-RNA positive episodes were considered as acute hepatitis C, while those negative for both markers were classified as acute non-A, non-B, non-C hepatitis. On comparing acute hepatitis C with the non-A, non-B, non-C episodes, no significant differences were found in the presence of jaundice, mean maximum alanine-aminotransferase (ALT) levels and positivity of markers of past hepatitis B virus (HBV) infection. However, patients with hepatitis C were significantly younger than those with non-A, non-B, non-C hepatitis (p=0.002). Male sex (78.1% vs. 35.3%; p=0.001), history of parenteral exposure (90.6% vs. 11.8%; p=0.0001), and progression to chronicity (73.4% vs. 5.9%; p=0.0001) were significantly more frequent in the HCV-related group. Although other possibilities cannot be excluded, these results suggest that there might be a different infectious agent implicated in the etiology of acute non-A, non-B, non-C hepatitis. This unidentified agent appears to be transmitted by the parenteral route with a lower frequency than HCV and to be responsible for acute hepatitis with a severity similar to that of acute hepatitis C but with a lower chronicity rate.

In 2007, a large goat-farming-associated Q fever outbreak occurred in the Netherlands. Data on the clinical outcome of Dutch Q fever patients are lacking. The current advocated follow-up strategy includes serological follow-up to detect evolution to chronic disease and cardiac screening at baseline to identify and prophylactically treat Q fever patients in case of valvulopathy. However, serological follow-up using commercially available tests is complicated by the lack of validated cut-off values. Furthermore, cardiac screening in the setting of a large outbreak has not been implemented previously. Therefore, we report here the clinical outcome, serological follow-up and cardiac screening data of the Q fever patients of the current ongoing outbreak. The implementation of a protocol including clinical and serological follow-up at baseline and 3, 6 and 12 months after acute Q fever and screening echocardiography at baseline. Eighty-five patients with acute Q fever were identified (male 62%, female 38%). An aspecific, flu-like illness was the most common clinical presentation. Persistent symptoms after acute Q fever were reported by 59% of patients at 6 months and 30% at 12 months follow-up. We observed a typical serological response to Coxiella burnetii infection in both anti-phase I and anti-phase II IgG antibodies, with an increase in antibody titres up to 3 months and a subsequent decrease in the following 9 months. Screening echocardiography was available for 66 (78%) out of 85 Q fever patients. Cardiac valvulopathy was present in 39 (59%) patients. None of the 85 patients developed chronic Q fever. Clinical, serological and echocardiographic data of the current ongoing Dutch Q fever outbreak cohort are presented. Screening echocardiography is no longer part of the standard work-up of Q fever patients in the Netherlands.

Pneumopericardium, the presence of air in the pericardial space, is a rare disorder that is usually caused by trauma. We describe a patient given induction chemotherapy for acute myelogenous leukemia who developed pulmonary aspergillosis that resulted in pericarditis and pneumopericardium. He responded to antifungal treatment and recovered from granulocytopenia, but died early during the next course of chemotherapy. Two other reported cases of pneumopericardium associated with pulmonary aspergillosis are summarized.

Plasma levels and renal excretion of sulphonamide and trimethoprim following oral administration of co-trimazine (410 mg sulphadiazine + 90 mg trimethoprim) and co-trimoxazole (800 mg sulphamethoxazole + 180 mg trimethoprim) were monitored in healthy volunteers after a single dose and in the steady state after 12-hourly dosage. The plasma levels of free, non-protein bound components after co-trimazine were approximately half those after co-trimoxazole and thus correlated with the doses given. Urine recovery of trimethoprim was better after cotrimazine (70%) than after co-trimoxazole (58%). Sixty-six percent of the sulphadiazine was recovered as unchanged, active sulphonamide in the urine compared with only 13% of the sulphamethoxazole. Consequently, the sulphonamide levels of sulphadiazine were 2.5 times those of sulphamethoxazole. With respect to plasma half-life after the first dose, sulphadiazine with 8.0 hours was closer to trimethoprim with a half-life of 8.8 hours after cotrimazine and 9.6 hours after co-trimoxazole than to the half-life of sulphamethoxazole which was 7.7 hours. The distribution volume of sulphadiazine was closer to that of trimethoprim than was that of sulphamethoxazole. On the basis of these characteristics, it has been concluded that sulphadiazine is more suitable for a fixed combination tablet with trimethoprim than sulphamethoxazole, particularly for the treatment of urinary tract infections. Some renal tubular reabsorption occurs with both unchanged sulphonamides but is more pronounced with sulphamethoxazole. The solubilities of the sulphonamides and their acetylated metabolites at acid urinary pH indicate that therapy with co-trimazine is at least as safe as with co-trimoxazole. With the former drug, the result of scrutiny for crystals after dosage until the steady state was negative, whereas crystals of acetylated sulphamethoxazole were detected and verified chemically in two of eight subjects.

Circulatory secretory non-pancreatic phospholipase A2 (snp-PLA2) was measured prospectively at the onset (day 0) of severe sepsis in 52 patients as well as on day 1 and 2 in 25 patients, in order to answer two questions: 1) does the snp-PLA2 plasma concentration differ according to the type and severity of infection? 2) what is the relation between snp-PLA2 and other mediators involved in severe sepsis, such as endotoxin, cytokines (TNFα, IL-1β, IL-6) and thromboxane B2 (the stable metabolite of thromboxane A2)? On day 0, the snp-PLA2 circulatory level was 78±17 nmol/min/ml in patients with severe sepsis as compared to 3.5±2 nmol/min/ml in 40 healthy volunteers. There was no statistical difference according to the outcome, the presence of shock, or the type of infection on day 0. However, snp-PLA2 remained elevated or even increased in patients who ultimately died, while it decreased in survivors (p=0.01 by ANOVA). The cytokine profiles during the 2-day follow-up were similar to that of snp-PLA2, but the differences were not statistically significant between survivors and non-survivors. No correlation was found between snp-PLA2 and other mediators for either initial or peak values.

One hundred and twenty women, aged between 18 and 90 years, with a history of at least four episodes of symptomatic urinary tract infection in the preceding 12 months, were randomized in an open, prospective study to prophylactic treatment with cefaclor 250 mg at bedtime or macrocrystalline nitrofurantoin 50 mg at bedtime for 12 months. Ninety-seven (49 taking cefaclor, 48 taking macrocrystalline nitrofurantoin) were assessed for efficacy; 80% of these were symptomatically improved and remained abacteriuric during the period of prophylaxis. Symptomatic attacks while patients were taking prophylaxis occurred at least five times less often than before prophylaxis had started. Seventy percent of the patients continued in an improved condition after having stopped prophylaxis. All 120 patients were assessed for adverse events; these were twice as frequent in patients taking macrocrystalline nitrofurantoin (20% vs. 10%), but only 11 patients (three taking cefaclor, eight taking macrocrystalline nitrofurantoin) withdrew from the study. Due to the small numbers of patients experiencing adverse events, these differences are not statistically significant. No significant changes in haematological or biochemical parameters were found during or after the end of the 12-month course. The 22 patients assessable for efficacy who had a non-obstructive radiological abnormality responded as well to prophylaxis as those with no detectable abnormality. Long-term, low-dose prophylaxis with a suitable antimicrobial agent is highly effective management for patients with recurrent urinary tract infections, and can appropriately be provided by the family doctor. Prophylaxis given for 1 year gives better results than when given for 6 months.

Fluoroquinolones are known to penetrate well into the infectious foci such as lung mucosa, epithelial lining fluid and alveolar macrophages achieving higher target site concentrations than the corresponding serum levels. In order to intergrate the in vitro antibacterial activity and pharmacokinetics of moxifloxacin and levofloxacin, their bactericidal efficacy was assessed by simulating human serum and lung tissue concentrations using Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae as indicator organisms. The bacteria were exposed to fluctuating moxifloxacin and levofloxacin concentrations simulating the drug levels in serum, lung mucosa, epithelial lining fluid and alveolar macrophages. The following parameters were deduced from the kill curves: area under the bactericidal kill curve normalized to the initial inoculum (AUBKC norm), the time needed to reduce the inoculum by 3 log10 titers, and the initial bactericidal activity. In general, all these three parameters were for all the bacterial isolates having been exposed to moxifloxacin concentration dependent. In contrast, beyond a levofloxacin concentration of optimal bactericidal effect, higher drug concentrations did not further augment the bactericidal activity of levofloxacin. These data demonstrate that not all fluoroquinolones share the same pharmacodynamic targets needed to maximize their antibacterial effect.