[Management of surgical therapy for advanced hidradenitis suppurativa with special consideration of perioperative antibiotic treatment - a questionnaire study]. / Management der chirurgischen Therapie der fortgeschrittenen Hidradenitis suppurativa unter besonderer Berücksichtigung der perioperativen Antibiose ­ Eine Fragebogenstudie.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease, which affects areas of the body that bear apocrine glands. In extensive cases, a combination of surgical and antibiotic treatment is often needed. Studies are available on the effects of clindamycin, also in combination with rifampicin, or tetracyclines. However, there are few precise recommendations for the perioperative application of antibiotic agents. PATIENTS/MATERIAL AND METHODS: An anonymous survey was conducted to determine the current status quo of perioperative antibiotic treatment. Physicians and surgeons were surveyed who worked at a department for plastic surgery, general surgery or dermatology in the German-speaking area. The questionnaire itself was created with Limesurvey© and was sent out to qualified departments, with the help from federal ministries of health. The responses were statistically analysed with IBM® SPSS® version 23. RESULTS: In most cases, the antibiotic treatment started before surgical intervention. Bacterial swabs were the most important factor in the selection of antibiotic agents. Most of theparticipants adjusted the treatment to the microbiological results, regardless of the chosen moment of application. Clindamycin was the most often used topical and systemic agent. The combination with rifampicin was most common. Adalimumab was the most commonly used antibody against tumor necrosis factor-alpha (TNF-α). In nearly half of the cases, antibodies were combined with antibiotics, and then the duration of treatment was usually longer. The extent of the disease was the most important factor for the necessity of surgical interventions. The wide excision of the whole affected area with subsequent healing by secondary intention was the surgical method of choice in all but one area. CONCLUSION: This study has shown that there are significant differences in the treatment between disciplines and countries. On the one hand, the disease severity, on the other hand, individual experience and preferences affect the treatment. Depending on the discipline that determined the therapy, some treatments are provided more rarely or not at all. Revised and up-to-date guidelines embodying all relevant disciplines would be desirable for a standardised therapy.

Empirical antimicrobial treatment in haemato-/oncological patients with neutropenic sepsis.

Neutropenic sepsis in haemato-/oncological patients is a medical emergency, as infections may show a fulminant clinical course. Early differentiation between sepsis and febrile neutropenic response often proves to be challenging. To assess the severity of the illness, different tools, which are discussed in this article, are available. Once the diagnosis has been established, the correct use of early empirical antibiotic and antifungal treatment is key in improving patient survival. Therefore, profound knowledge of local resistance patterns is mandatory and carefully designed antibiotic regimens have to be established in cooperation with local microbiologists or infectious diseases specialists. In the following, identification, therapy and management of high-risk, neutropenic patients will be reviewed based on experimental and clinical studies, guidelines and reviews.

A case report of septic shock syndrome caused by S. pneumoniae in an immunocompromised patient despite of vaccination.

BACKGROUND AND CASE PRESENTATION: We report a case of septic shock syndrome caused by Streptococcus pneumoniae in a patient who had undergone splenectomy due to an autoimmune lymphoproliferative syndrome (ALPS), which is characterized as a dysfunction of immunoregulation. Although the patient was vaccinated with a conjugated polysaccharide vaccine after the splenectomy, he was still susceptible to S. pneumoniae infection, because the isolated serovar (24F), a serovar long thought to be apathogenic, is not covered by any vaccine currently approved, neither a conjugated nor an unconjugated polysaccharide one. CONCLUSIONS: This case demonstrates that, due to presence of different serovars, also infections with bacteria against which patients are vaccinated have to be considered as differential diagnosis. Although vaccine development has extended the coverage of S. pneumoniae from 7 to 23 serovars within recent years, there is still demand for novel vaccines which can provide broader protection also against so-thought "apathogenic" strains, especially for groups at high risk.

Direct sternal administration of Vancomycin and Gentamicin during closure prevents wound infection.

OBJECTIVES: Deep sternal wound infection is still a major complication in patients undergoing cardiac surgery. We previously identified mammary artery harvesting as a risk factor for decreased antibiotic tissue penetration. In addition, other risk factors including diabetes may inhibit sufficient tissue penetration of perioperative antibiotic prophylaxis. A novel closure protocol applying 2 topical antibiotics and further recommendations for sternal wiring was introduced at our department to decrease the incidence of sternal wound infections. METHODS: A 12-month period prior to (March 2013-February 2014) and after (July 2014-June 2015) the introduction of a novel sternal closure protocol was studied. All sternal wound infections resulting from an operation during this period were analysed. The closure protocol consisted of the intra-sternal application of vancomycin and the subcutaneous application of gentamicin. Furthermore, we increased the number of sternal wires for more uniform distribution of lateral forces. RESULTS: Patients in both groups were comparable regarding demographic data and risk factors. Fifty-three out of 919 patients operated prior to the protocol change developed an infection (5.8%). The introduction of the novel sternal closure protocol reduced this number to 19 out of 932 patients (2.0%; P < 0.001). A binary regression including common risk factors revealed a strong independent risk reduction by the novel protocol (OR 0.322, P < 0.001). The number of sternal wires was not significant in this analysis. CONCLUSIONS: The topical application of 2 antibiotic agents significantly reduced sternal wound infection. However, the results of this trial should be confirmed in a randomized trial.

[Guidelines for vaccination of immunocompromised individuals]. / Impfungen bei Immundefekten/Immunsuppression - Expertenstatement und Empfehlungen.

Immunosuppression of various origins is associated with an increased risk of infection; therefore the prevention of infectious diseases by vaccination is especially important in immunocompromised patients. However, the response to vaccinations is often reduced in these risk groups and the application of live vaccines is contraindicated during immunosuppression.In the following expert statement, recommendations for vaccination were created on the basis of current evidence and theoretical/immunological considerations. A first, general part elaborates on efficacy and safety of vaccinations during immunosuppression, modes of action of immunosuppressive medications and recommended time intervals between immunosuppressive treatments and vaccinations. A core piece of this part is a graduation of immunosuppression into three stages, i. e. no relevant immunosuppression, mild to moderate and severe immunosuppression and the assignment of various medications (including biologicals) to one of those stages; this is followed by an overview of possible and necessary vaccinations in each of those stages.The second part gives detailed vaccination guidelines for common diseases and therapies associated with immunosuppression. Primary immune deficiencies, chronic kidney disease, diabetes mellitus, solid and hematological tumors, hematopoetic stem cell transplantation, transplantation of solid organs, aspenia, rheumatological-, gastroenterologic-, dermatologic-, neurologic diseases, biologicals during pregnancy and HIV infection are dealt with.These vaccination guidelines, compiled for the first time in Austria, aim to be of practical help for physicians to facilitate and improve vaccination coverage in immunocompromised patients and their household members and contact persons.

Cefazolin and linezolid penetration into sternal cancellous bone during coronary artery bypass grafting.

OBJECTIVES: Deep sternal wound infection is a severe complication after cardiac surgery. Insufficient antibiotic target site concentrations may account for variable success of perioperative prophylaxis. Therefore, we measured perioperative penetration of cefazolin and of linezolid into sternal cancellous bone after sternotomy in coronary artery bypass grafting (CABG) patients by in vivo microdialysis. METHODS: Nine patients underwent CABG using a skeletonized left internal mammary artery. Standard antibiotic prophylaxis consisted of 4 g cefazolin prior to skin incision and additional 2 g during skin closure. In addition, 600 mg of linezolid were administered prior to skin incision and after 12 h for study purposes. Two microdialysis probes were inserted into the sternal cancellous bone (left and right side) after sternotomy. RESULTS: First mean peak cefazolin and linezolid plasma concentrations were 273 ± 92 µg/ml and 22.1 ± 8.9 µg/ml, respectively. Mean peak concentrations of antibiotics in sternal cancellous bone on the left and right sternal side were 112 ± 59 µg/ml and 159 ± 118 µg/ml for cefazolin and 10.9 ± 4.0 µg/ml and 12.6 ± 6.1 µg/ml for linezolid, respectively. Cefazolin exceeded the required tissue concentrations for relevant pathogens by far, but linezolid did not gain effective tissue concentrations in all patients for some relevant pathogens. Mammary artery harvesting had no significant effect on antibiotic tissue penetration. CONCLUSIONS: Direct measurement of antibiotic concentration in sternal cancellous bone with in vivo microdialysis is technically demanding but safe and feasible. We could demonstrate sufficient antibiotic coverage with our standard cefazolin-dosing regimen in the sternal cancellous bone during cardiac surgery. Mammary artery harvesting had no clinically relevant effect on tissue penetration. Linezolid concentrations were not sufficient for some relevant pathogens.

Fatal skin and pulmonary infection caused by Hormographiella aspergillata in a leukaemic patient: case report and literature overview.

Invasive systemic fungal infections are a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation. We report the case of a fatal infection with Hormographiella aspergillata in a patient undergoing allogenic peripheral blood stem cell transplantation for acute myeloid leukaemia.

Pneumonia in a patient with familial Mediterranean fever successfully treated with anakinra--case report and review.

We report the case of a 35-years-old renal transplant patient known to have familial Mediterranean fever with serum amyloid A (SAA)-amyloidosis, who presented with his second episode of bilateral pneumonia. As antimicrobials failed to control the first episode of pneumonia and all studies done were non-contributory, we attributed the condition to the highly active Mediterranean fever presumably resistant to colchicine and treated the patient with the interleukin-1 receptor antagonist anakinra: the patient substantially improved by clinical symptoms, chemistry and radiological evidence within no more than 2 days and was discharged in good health after 4 days.

Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha as acne inversa therapy.

We present a case of fever, brain abscesses, and Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha (TNF-α) therapy in a 21-year-old acne inversa patient currently taking long-term dapsone. To the best of our knowledge, this is the first report describing such a case. During antimicrobial therapy, the patient developed systemic varicella infection with severe thrombocytopenia.

Multiple-dose pharmacokinetics of anidulafungin during continuous venovenous haemofiltration.

BACKGROUND: Clinical studies support a role for anidulafungin as first-line treatment of invasive candidiasis in critically ill patients and postulate no need for dose adjustments in mild to severe renal failure. Although intensive care patients requiring renal replacement therapy are at particular risk of invasive fungal infection, no pharmacokinetic data on anidulafungin during continuous venovenous haemofiltration (CVVHF) are available. PATIENTS AND METHODS: Ten patients with CVVHF due to acute renal failure were included. Anidulafungin was infused on 3 consecutive days starting with a loading dose of 200 mg on day 1, followed by doses of 100 mg on each of days 2 and 3. During the 72 h study phase of CVVHF, blood and ultrafiltrate samples were collected at corresponding times. Anidulafungin concentrations were determined by HPLC. RESULTS: Peak plasma concentrations were reached 3 h after the start of infusion and were 8.5±3.6 mg/L at the pre-filter port. The mean arterial area under the curve (AUC0-24) of the study population was 109.9±49.82 mg·h/L, the total clearance was 1.08±0.41 L/h, the volume of distribution was 41.97±22.64 L and the elimination half-life was 28.78±10.40 h. Anidulafungin was not filtered, but CVVHF resulted in a substance loss of ∼20%, due to adherence to synthetic surfaces. CONCLUSIONS: Pharmacokinetics of anidulafungin during CVVHF resembled findings in healthy adults and adults with fungal infections. Therefore we recommend a loading dose of 200 mg intravenous anidulafungin on the first day and 100 mg on consecutive treatment days in patients during CVVHF.

[Questionnaire surveying nephrologists on drug dose adjustment in patients with impaired kidney function]. / Umfrage zur Arzneimitteldosierung bei Niereninsuffizienz unter nephrologisch tätigen Arzten.

OBJECTIVE: Our intention was to assess knowledge and requirements related to drug dose adjustment in patients with impaired kidney function. METHOD: In 2005, we sent a questionnaire containing 22 questions to nephrologists in Germany and Austria. With 77 responses, the study was not representative. However, it was probably of importance for the target group of practising physicians and potential users of a future drug information system. RESULTS: Only 28% of the responding colleagues use the package inserts; these are obviously not considered to be an obligatory guideline for dose adjustment. The most common dosing problems (p < 0.05) were associated with anti-infective (48%) and anti-cancer drugs (25%). The greatest problems with dosing were encountered within intensive care units (29%). The risk of excessive dosing is estimated significantly more serious than the risk of underdosing (51% vs. 23%, p = 0.02). There was support for the statement that for cephalosporin antibiotics the trough levels are more important than peak levels (58% vs. 27%, p < 0.01). However, only 8% knew that in patients with impaired kidney function, trough concentrations of aminoglycosides and vancomycin need to be higher than in patients with normal kidney function for adequate peak levels to be obtained. Forty-five percent of respondents erroneously presumed that ceftriaxone must be adjusted to the kidney function. Half of the respondents were incorrect in assuming that ceftriaxone or moxifloxacin would be removed by dialysis. CONCLUSIONS: We see the need for more knowledge-based information on drug dosing in patients with kidney impairment and those in the intensive care unit. The risk to life posed by underdosage might be underestimated, especially for anti-infective drugs.

Intra-cystic drug concentration of albendazole sulphoxide in patients with Echinococcus granulosus cysts.

Albendazole therapy--alone or in combination with surgery--remains the standard of care for human echinococcosis depending on the stage of disease. However, only limited data are available on target site concentrations in liver cysts and data for non-liver cysts are lacking. We report on intra-cystic concentrations of the biologically active metabolite albendazole sulphoxide in non-liver cysts indicating a relative intra-cystic drug concentration of 48-156% compared with plasma levels. These data are evidence for a satisfactory penetration of albendazole sulphoxide into Echinococcus cysts localized in other organs than the liver and underline the usefulness of albendazole therapy for this indication.

Influence of vancomycin on renal function in critically ill patients after cardiac surgery: continuous versus intermittent infusion.

BACKGROUND: Vancomycin is frequently used in clinical practice to treat severe wound and systemic infections caused by Gram-positive bacteria after cardiac surgery. The drug is excreted almost entirely by glomerular filtration and might exhibit nephrotoxic side effects. This study compared the nephrotoxic impact of vancomycin during continuous versus intermittent administration. METHODS: The authors analyzed 149 patients admitted to the intensive care unit during a 5-yr period. All patients were treated at the intensive care unit after elective open heart surgery. Thirty patients received a dosage of 1325 +/- 603 mg/d vancomycin (range 300-3400 mg/d) by intermittent infusion, and 119 patients received a mean dosage of 1935 +/- 688 mg/d (range 352-3411 mg/d) by continuous infusion. RESULTS: Nephrotoxicity occurred in 11 patients (36.7%) in the intermittent treatment group and in 33 patients (27.7%) in the continuous treatment group (P = 0.3; 95% CI = 0.283). Continuous veno-venous hemofiltration after vancomycin administration was required for 9 patients (9 of 30; 30%) in the intermittent treatment group and for 28 (28 of 119; 23.5%) in the continuous treatment group (P = 0.053; 95% CI = 0.256). A change of one unit (1 mg/l) in vancomycin serum concentration (DeltaVancoC) induced an average change of 0.04 mg/dl in creatinine (DeltaCrea) in the intermittent treatment group versus 0.006 mg/dl in the continuous treatment group (P < 0.001). CONCLUSIONS: The data show that both the intermittent and also the continuous application modality of vancomycin are associated with deterioration of renal function in critically ill patients after cardiac surgery. However, continuous infusion showed the tendency to be less nephrotoxic than the intermittent infusion of vancomycin.

Catastrophic graft-versus-host disease after lung transplantation proven by PCR-based chimerism analysis.

Acute graft-versus-host disease (GvHD) is a rare complication after solid organ transplantation. We describe a 52-year-old female developing neutropenia and fever 48 days after single lung transplantation for chronic obstructive pulmonary disease. Bone marrow (BM) biopsy suggested drug-induced marrow failure, so immunosuppression was reduced. Five days later a maculopapular skin rash was observed, progressing to a generalized erythema with desquamation. Skin biopsy was suspectable for GvHD, so immunosuppression was re-initiated. PCR-based chimerism analysis of BM revealed 78% donor cells. Intensified immunosuppression resulted in temporary improvement, but BM aplasia recurred and the patient experienced severe GvHD of gut and liver. Despite extensive immunosuppression the patient died from multi-organ failure 99 days after transplantation. This report describes the occurrence of neutropenia as an early presenting sign of acute GvHD after lung transplantation. We therefore recommend incorporating GvHD in the differential diagnosis of neutropenia after solid organ transplantation, calling for early chimerism analyses.

Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery.

Soft tissue infections constitute a serious complication following surgery in diabetic patients and frequently require the administration of vancomycin. However, despite antibiotic treatment, mortality of patients with postoperative infections remains high and might be related to an impaired penetration of anti-infective agents to target tissues. Therefore, the present study was designed to measure vancomycin tissue concentrations in six diabetic and six nondiabetic patients after cardiac surgery. Vancomycin was administered as a continuous intravenous infusion at an infusion rate of 80 to 120 mg/h. Vancomycin concentrations in soft tissues and plasma were measured in all patients during steady state as "therapeutic window" concentrations in plasma by microdialysis on day 8+/-4 after initiation of vancomycin treatment. Vancomycin tissue concentrations in diabetic patients were significantly lower than in nondiabetics (3.7 mg/liter versus 11.9 mg/liter; P=0.002). The median vancomycintissue/vancomycinplasma concentration ratio was 0.1 in diabetic patients and 0.3 in nondiabetics (P=0.002). Our study demonstrated that vancomycin penetration into target tissues is substantially impaired in diabetic patients versus nondiabetics. Insufficient tissue concentrations could therefore possibly contribute to failure of antibiotic treatment and the development of antimicrobial resistance in diabetic patients.

Brief report: practicability and safety of amphotericin B deoxycholate as continuous infusion in neutropenic patients with hematological malignancies.

Fungal infections are a major cause of morbidity and mortality in patients with hematological malignancies. Candida and Aspergillus species are the most important opportunistic fungal pathogens in this patient population. Amphotericin B is the treatment of choice, but its administration is often hampered by severe side-effects, which may be reduced by continuous infusion of this drug. We describe 17 consecutive patients with hematological malignancies, suffering from fever of unknown origin with possible fungal infections, treated with amphotericin B as continuous infusion compared with a control group of 10 patients treated with conventional rapid infusion of amphotericin B over 2 - 6 h. No acute side-effects or severe nephrotoxicity were observed during continuous infusion of amphotericin B. Target doses were reached faster in patients with continuous infusion of amphotericin B than in patients with rapid infusion. We conclude that continuous infusion of amphotericin B is safe in neutropenic patients with hematological malignancies.

Bedside exclusion of clinically significant recirculation volume during venovenous ECMO using conventional blood gas analyses.

STUDY OBJECTIVE: To investigate prospectively whether blood gas samples drawn from extracorporeal membrane oxygenation (ECMO) cannulae help to exclude at least clinically significant recirculation volumes in patients with acute respiratory failure. DESIGN: Feasibility study. SETTING: Intensive care unit at a university-affiliated hospital. PATIENTS: Ten consecutive adult patients suffering from severe respiratory failure and undergoing ECMO. INTERVENTIONS: The drawing (venous) ECMO cannula was placed into the inferior vena cava via a femoral vein, and the oxygenated blood was returned via the right subclavian vein by supraclavicular access directly into the right atrium. Blood gas samples were obtained from both cannulae. MEASUREMENTS AND MAIN RESULTS: The median arterial oxygen tension (PaO(2)) obtained from the arterial cannula was 537 mmHg (range, 366 to 625 mmHg), the median mixed venous oxygen tension (PvO(2)) drawn from the venous cannula was 42 mmHg (range, 25 to 54 mmHg), which was less than 10% of that observed in the arterial cannula, and also within the physiologic range of PvO(2). The ECMO flow necessary to maintain patients' oxygen saturation above 90% (4.1 L/min; range, 1.95 to 5.8 L/min) was significantly lower than the patients' cardiac output (CO; 6.2 L/min; range, 4.1 to 7.9 L/min; p < 0.001). CONSLUSIONS; We recommend obtaining blood gas samples-immediately after initiation of ECMO-from both cannulae. A PvO(2) within physiologic range and below 10% of PaO(2) rules out any clinically relevant recirculation volume.