Vacuum-assisted closure therapy of paradoxical reaction in tuberculous lymphadenopathy caused by Mycobacterium africanum.

A 26-year-old HIV-negative male from Ghana was treated for cervical, intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all first-line antituberculous drugs. Four weeks after the beginning of directly observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the right cervical lymph node increased in size, liquefied and caused a spontaneous fistula. A biopsy of the necrotized lymph node revealed rare acid-fast bacilli with a positive PCR for Mycobacterium tuberculosis complex. After debridement, vacuum-assisted closure therapy was performed for 6 weeks. Five months after the beginning of antituberculous therapy, a second paradoxical reaction occurred, with painful swelling of two contralateral supraclavicular lymph nodes. Extirpation of one node yielded a positive PCR for M. tuberculosis complex; the culture was negative. Antituberculous treatment was continued, and additional treatment with oral prednisolone 20 mg daily for 1 month tapering over 10 weeks was introduced, resulting in a decrease in lymphadenopathy. Antituberculous treatment was continued for a total of 9 months. The outcome was favorable, no further lymphadenopathy occurred over the following 6 months.

[Travel-associated pneumonias]. / Pneumonien mit Reiseanamnese.

Respiratory infections are responsible for up to 11% of febrile infections in travellers or immigrants from tropical and subtropical regions. The main pathogens are the same as in temperate climate zones: Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, influenza viruses, Legionella pneumophila. However, some pulmonary diseases can be attributed to bacterial, parasitic, viral or fungal pathogens that are endemic in tropical and subtropical regions. The most commonly imported infections are malaria, dengue, and tuberculosis. Pulmonary symptoms and eosinophilia in returning travellers and migrants may be caused by several parasitic infections such as Katayama syndrome, Loeffler syndrome, tropical pulmonary eosinophilia, amebiasis, paragonimiasis, echinococcosis, and toxocariasis. In Asia, Tsutsugamushi fever is transmitted by chiggers, spotted fever rickettsiae are transmitted by ticks. Transmission of zoonotic diseases occurs mainly via contact with infected animals or their excretions, human-to-human transmission is generally rare: MERS-CoA (dromedary camels), pulmonary hantavirus infection (rodents), tularemia (rabbits and hares), leptospirosis (rats), Q-fever (sheep and goats), very rarely anthrax (hides of ruminants) and pest (infected rats and wildlife). Inhalation of contaminated dust can cause infections with dimorphic fungi: histoplasmosis (bat guano) and coccidioidomycosis in America and parts of Africa, blastomycosis in America. Some infections can cause symptoms years after a stay in tropical or subtropical regions (melioidosis, tuberculosis, histoplasmosis, schistosomiasis-associated pulmonary hypertension). Noninfectious respiratory diseases caused by inhalation of high amounts of air pollution or toxic dusts may also be considered.

Ciprofloxacin reduces the risk of hemolytic uremic syndrome in patients with Escherichia coli O104:H4-associated diarrhea.

BACKGROUND: Whether antibiotic treatment in patients with enterohemorrhagic Escherichia coli (EHEC)-associated diarrhea influences the risk of hemolytic uremic syndrome (HUS) has still to be elucidated. PATIENTS AND METHODS: During the EHEC epidemic which occurred in northern Germany in spring 2011, 24 patients with E. coli O104:H4 infection were treated at our hospitals, 19 of whom developed HUS. The use of antibiotics before and after the onset of HUS was documented, and the outcome in patients with and without antibiotic treatment was evaluated. RESULTS: Of the 24 patients with EHEC-associated diarrhea, seven received antibiotics before any signs of HUS were present (ciprofloxacin, cefotaxime, amoxicillin and/or metronidazole). Four of these seven patients (57 %) and 15 of the 17 patients (88 %) who were treated without antibiotics developed HUS (p = 0.12). Microbiological testing showed all E. coli O104:H4 to be extended-spectrum beta lactamase producers and thus susceptible only to fluoroquinolones, aminoglycosides and carbapenems. Two of the five patients (40 %) treated with ciprofloxacin and 17 of the 19 patients (89 %) treated without ciprofloxacin developed HUS (p = 0.043). CONCLUSION: In our E. coli O104:H4-infected patients, treatment of diarrhea with antibiotics did not increase the risk of HUS. Significantly fewer patients treated with ciprofloxacin developed HUS than patients who did not receive ciprofloxacin.

Interleukin-10: effects on phagocytosis and adhesion molecule expression of granulocytes and monocytes in a comparison with prednisolone.

Interleukin-10 (IL-10) has potent anti-inflammatory and immunosuppressive properties. The potential therapeutic benefit may be compromised by the down-regulation of the non-specific immune system and an increased risk of infection. We studied the effects of IL-10 on important functions of native and granulocyte-macrophage colony-stimulating factor (GM-CSF) activated neutrophils and monocytes, namely phagocytosis and membrane expression of the beta superset2-integrins and of the intercellular adhesion molecule-1 (ICAM-1). In order to simulate the in vivo situation closely, we used whole blood flowcytometric assays. The effects of IL-10 (0.05, 1, 10, 100 ng/ml) were compared to those of prednisolone (10 superset-8-10 superset-5 Mol/l), an approved immunosuppressive drug which is known to impair phagocyte function. - Incubation with IL-10 for three hours significantly attenuated the ability of neutrophils to phagocytose E.coli, particularly in lower concentrations. On the other hand, high IL-10 concentrations (10, 100 ng/ml) slightly augmented monocyte phagocytosis. Similarly, expression of the beta subset2-integrins and of ICAM-1 on monocytes was markedly enhanced with IL-10 concentrations in the range from 1 to 100 ng/ml and IL-10 showed strong synergistic effects with GM-CSF in the enhancement of monocyte receptor expression. Neutrophil adhesion molecule expression was not affected. Prednisolone suppressed the phagocytosis of both cell types in a dose-dependent fashion but hardly altered the receptor numbers. Our study indicates that IL-10 can behave as a de-activator as well as an activator on the non-specific immune system, depending on the cell type and the concentration.

In vitro effects of interleukin-10, prednisolone, and GM-CSF on the non-specific immune function of human polymorphonuclear leucocytes and monocytes.

A wide range of immune-modulating effects make IL-10 a potential therapeutic option in the treatment of numerous diseases pathophysiological based on a dysregulation of cytokine production. The background of this study was to investigate, whether the beneficial effects of a therapeutic immunosuppression with IL-10 may be countered by an increased risk for infections due to impaired effector cell functions of unspecific immunity. We demonstrated the in vitro effects of IL-10 on phagocytosis (P), intracellular killing (K), and chemotactic activity (C) by human neutrophils (PMN) and monocytes (MON) using Candida albicans as test strain and compared the results to the effects of prednisolone and GM-CSF. IL-10 reduced significantly the intracellular killing rate of PMN compared to untreated phagocytes (60 +/- 16% versus 68 +/- 13%, mean +/- SD, p = 0.0002). High dose IL-10 (100 ng/ml) had a stimulating effect on the percentage of phagocytizing MON (70.2 +/- 12.7% vs. 66.9 +/- 14.2%, p = 0.0436), without impairing intracellular killing. Prednisolone reduced significantly the Candida uptake by MON (57 +/- 18.1% vs. 66. 9 +/- 14.2%, p = 0.0019). In contrast to prednisolone, neither MON nor PMN chemotaxis was suppressed by IL-10. In conclusion, IL-10 had only marginal immunosuppressive effects on the unspecific immunity compared to prednisolone.

Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate.

In an open, randomized, triple crossover study, the effects of cisapride and sucralfate on the pharmacokinetics of sparfloxacin were assessed. Fifteen healthy volunteers received 400 mg of sparfloxacin as a single oral dose on day 0. In a random order, concomitant doses of 10 mg of cisapride three times daily from day -2 to day 2 and 1 g of sucralfate four times daily from day -2 to day 0 were administered. Sparfloxacin concentrations were measured by bioassay and high-performance liquid chromatography. Pharmacokinetic parameters for sparfloxacin alone were as follows (mean +/- standard deviation): maximum concentration of drug in serum (C(max)), 1.27 +/- 0.39 microg/ml; time to C(max) (T(max)), 4.1 +/- 1.9 h; area under the concentration-time curve (AUC), 35.0 +/- 9.7 microg x h/ml; mean residence time, 28.5 +/- 5.7 h; half-life (t1/2), 20 +/- 4 h; urinary recovery (UR x f), 11.0% +/- 2.7%; and metabolite-sparfloxacin ratio in urine, 2.6. For the cisapride group there was a significant decrease in the sparfloxacin T(max) (1.9 +/- 2.1 h) and a significant increase in C(max) (1.74 +/- 0.73 microg/ml). The QTc interval for patients receiving sparfloxacin and cisapride was prolonged by 7.7% compared to the QTc interval during medication-free periods. Significant differences in the values for the group receiving sucralfate compared to the values for the group receiving sparfloxacin alone were found: C(max), 0.77 +/- 0.31 microg/ml; AUC, 18.6 +/- 5.8 microg x h/ml; t1/2, 26 +/- 10 h; and UR x f, 5.8 +/- 1.8%. Concomitant adminstration of cisapride accelerates the absorption and increases the peak concentration of sparfloxacin without having a significant effect on the extent of bioavailability. Coadministration of sucralfate leads to a 44% decrease in the bioavailability of sparfloxacin.

Comparative pharmacokinetics of dirithromycin and erythromycin in normal volunteers with special regard to accumulation in polymorphonuclear leukocytes and in saliva.

OBJECTIVE: In a randomized cross-over study, we assessed pharmacokinetics and intracellular concentrations in polymorphonuclear leukocytes (PMN) and saliva of erythromycin and erythromycylamine, the active metabolite of dirithromycin. METHODS: Ten healthy volunteers received 1 g erythromycin b.i.d. or 500 mg dirithromycin qd for 5 days (wash out period, 35 days). Concentrations of erythromycin and erythromycylamine were measured in serum, urine, saliva, and granulocytes by bioassay and high-performance liquid chromatography (HPLC) on days 1, 3, and 5 of each study period, respectively. RESULTS: While maximal serum concentrations (Cmax) and the area under the data (AUDtot) of erythromycin were significantly higher (Cmax 1.44 mg.l-1, AUDtot 5.66 mg.h.l-1) than those of erythromycylamine (Cmax 0.29 mg.l-1, AUDtot 1.96 mg.h.l-1), erythromycylamine had a significantly higher mean residence time (21 h) than erythromycin (5.5 h). Erythromycylamine accumulated significantly more in PMN than erythromycin; the accumulation factor of erythromycylamine was 100 with a maximal intracellular concentration of 13.4 mg.l-1, whereas the maximal accumulation factor of erythromycin was 4 with a maximal intracellular concentration of 6.1 mg.l-1. There were no significant differences in maximal saliva concentrations (erythromycin 0.35 mg.l-1, erythromycylamine 0.31 mg.l-1).

Pneumocystis carinii pneumonia as a complication of immunosuppressive therapy.

BACKGROUND: Patients receiving immunosuppressive therapy with corticosteroids and cytotoxic agents may develop opportunistic infections such as Pneumocystis carinii pneumonia (PCP). This indicates a severe T-cell defect, but so far there are no established criteria for identifying patients at risk. PATIENTS AND METHODS: CD4+ and CD8+ T-lymphocyte counts were determined by flow cytometry in seven HIV-negative patients who developed PCP as a complication of immunosuppressive treatment. RESULTS: CD4+ T-lymphocyte counts (T-helper phenotype) were less than 200/microl in all seven patients (mean 90.6/microl). The markedly reduced CD4 counts measured in these patients are similar to those observed in organ transplant recipients who developed PCP during immunosuppressive therapy for prevention of graft rejection and in HIV-positive patients with PCP as an AIDS-defining illness. CONCLUSION: Measuring CD4+ T-lymphocyte counts may be helpful in determining the risk of PCP not only in HIV-positive patients, but also in patients receiving immunosuppressive therapy. The risk of acquiring PCP seems to increase when CD4+ lymphocyte counts drop below 200/microl, regardless of the underlying disease.

Levofloxacin pharmacokinetics and serum bactericidal activities against five enterobacterial species.

After oral administration of 500 mg of levofloxacin to 12 volunteers, we investigated the pharmacokinetics and serum bactericidal activities (SBAs) against five strains of members of the family Enterobacteriaceae. Pharmacokinetic data were as follows: maximum concentration in serum, 6.36 +/- 0.57 mg/liter; area under the concentration-time curve, 43.6 +/- 6.23 mg. h/liter; elimination half-life 4.23 +/- 0.87 h. SBAs were present for 24 h against Escherichia coli and Citrobacter freundii. The SBAs at 1, 12, and 24 h after administration against E. coli were 1:108, 1:29, and 1:7, respectively, and those against Citrobacter freundii were 1:74, 1:25, and 1:7, respectively. The SBAs were present for 12 h against the other three organisms tested. The SBAs against Serratia marcescens were 1:28 and 1:9 at 1 and 12 h, respectively; the SBAs against Klebsiella pneumoniae were 1:25 and 1:7 at 1 and 12 h, respectively; and the SBAs against Enterobacter cloacae were 1:24 and 1:10 at 1 and 12 h, respectively.