Potential Saving of Antibiotics for Respiratory Infections in Several European Countries: Insights from Market Research Data.

Antibiotics represent an essential pillar in the treatment of respiratory infections (RI). Overuse of antibiotics in avoidable cases and inappropriate application in bacterial infections facilitate treatment resistance, threatening their effectiveness and causing a significant healthcare challenge. We therefore assessed the savings potential for antibiotics in ambulant care of selected RI (bronchitis and cough, pharyngitis, rhinosinusitis) in several European countries based on market research data for the year 2019. Number of antibiotic packages sold in pharmacies varied, with highest values in Serbia and France, and lowest in Sweden and Switzerland. Selected RI contributed nearly half of overall ambulant antibiotic prescriptions, with around one fifth given for bronchitis and cough; the vast majority was estimated to be of viral origin with potentially avoidable antibiotic use. Antibiotic consumption for selected RI in eight European countries (Austria, Belgium, the Czech Republic, France, Germany, Poland, Slovakia, and Switzerland) amounted to nearly 100 million, with an overall savings potential between 66.2 and 83.7 million packages. The highest estimated volume of avoidable antibiotics was in France (44.7 million, 0.80 per capita), and lowest in Switzerland (1.4 million, 0.18 per capita). Due to substantial savings potential, prudent use of antibiotics and adequate application of alternatives should be promoted in daily practice.

18F-FDG PET/CT in the Initial Assessment and for Follow-up in Patients With Tuberculosis.

PURPOSE: The aim of this retrospective study was to assess the value of 18F-FDG PET/CT in the initial evaluation and follow-up of patients with tuberculosis (TB). PATIENTS AND METHODS: Thirty-five patients (18 men) with pulmonary or extrapulmonary TB were included. Diagnosis of TB was based either on histology or microbiological assessment in 32 patients and was based on typical morphological features of TB in CT and improvement on antimycobacterial medication in 3 patients. Eighty-eight 18F-FDG PET/CT scans were performed at initial assessment and during treatment, on a Siemens Biograph PET/CT. Diagnostic contrast-enhanced CT scans were performed on the 40-slice multidetector CT of the PET/CT scanner. Mean (SD) anti-TB treatment duration was 16.1 (8.9) months. RESULTS: The initial 18F-FDG PET identified 64 affected regions in 34 among 35 patients, whereas CT identified 34 affected organs in 23 patients. Matching image results between PET and CT were observed at first visit in 11 patients (31.4%), with relevant differences in 23 (65.7%). In 1 patient, both modalities remained negative. During follow-up 18F-FDG PET scans, we recorded 15 cases with remission of disease, 16 with residual disease (2 patients with multidrug-resistant infection), and 4 cases with progressive disease or delayed onset of adequate immunological response. In only 3 patients, both modalities, PET and CT, showed completely equivalent results. CONCLUSIONS: Both components of 18F-FDG PET/CT provide complementary information at initial evaluation and during follow-up; however, 18F-FDG showed more abnormal findings than CT. 18F-FDG PET/CT might be useful for the establishment of individualized treatment regimes, but this requires further prospective studies.

Infections caused by Candida krusei in five transplant and two surgical patients.

BACKGROUND: Candida krusei (Ck) may cause severe infections in immunocompromised hosts and is innately resistant to fluconazole. PATIENTS AND METHODS: During an 18-month period, seven patients with Ck infection were identified at our center. All were treated in the transplant intensive care unit. Candida isolates were grown on Sabouraud agar, and chromosomal DNA was extracted; clonality was investigated using random amplified polymorphic DNA-polymerase chain reaction with primers M13, OPA-18, and OPE-18. RESULTS: Among the patients with Ck infection, there were three pancreas recipients with intra-abdominal infection, one liver recipient with cholangitis, one lung recipient with pleural empyema, one patient with pleural empyema after esophageal perforation, and one case of pneumonia in a patient with a ventricular assist device. Treatment consisted of caspofungin (n = 3), voriconazole (n = 1), or a combination of the two (n = 2) together with surgery (n = 3) or pigtail catheter drainage (n = 3). One patient underwent drainage without antifungal treatment, and one patient did not have drainage. The infection was controlled in all cases. The patient with the assist device died from multiple organ dysfunction, the lung recipient died after four months from graft failure, and one pancreas graft was lost. Four patients (57%) harbored the same Ck strain. CONCLUSION: Solid organ recipients seem to be at particular risk for Ck infections; clonal outbreaks may occur in intensive care units.

Streptococcus milleri group isolates from blood cultures: consider surgical sepsis.

BACKGROUND: Streptococcus milleri group bacteria (SMG) frequently are involved in purulent infections, often resulting in abscess formation with a high recurrence rate. Blood stream infections with these organisms are infrequent. PATIENTS AND METHODS: Review of epidemiologic and clinical characteristics of SMG-related bacteremia. RESULTS: During a four-year period, 637 SMG-positive samples from 475 patients, including 45 positive blood cultures from 25 patients (7.1%), were identified. In one pediatric patient, the SMG was a contaminant, so 24 patients (5.1%) with 44 positive blood cultures (6.9%) were available for further evaluation. The study group consisted of 17 male and seven female patients with a median age of 56 years and a median hospital stay of 23 days (range 8-83 days). In 21 patients, monomicrobial SMG blood stream infection was found, whereas in three patients, polymicrobial infection was diagnosed (coagulase-negative staphylococci in two, Escherichia coli and Bacteroides fragilis in one). The source of the organism in the blood was intra-abdominal infection in six cases, soft tissue infection in another six cases, and cardiovascular and nervous system infection in three cases each. In the remaining cases, miscellaneous sources were identified. In 14 infected patients (58.3%), surgical interventions were performed before SMG bacteremia was diagnosed. All patients received antibiotic treatment with a median duration of 11.5 d (range 6-25 d). Five patients died, but no death was related directly to SMG infection. CONCLUSIONS: Sepsis with SMG is in most cases associated with surgical infection. Source control together with directed antibiotic therapy leads to an acceptable outcome. Immunosuppression and significant co-morbidities are common in patients with this type of infection.

Clostridium perfringens liver abscess after pancreatic resection.

BACKGROUND: Liver abscess is a rare complication after pancreatectomy. Clostridium perfingens is a rare cause of intrahepatic infections. CASE REPORT: A 65-year-old woman with pancreatic cancer underwent explorative laparotomy, during which encasement of the hepatic artery by the tumor was found. Neoadjuvant radiochemotherapy with capecitabine was started, which caused tumor regression, and duodenopancreatectomy was performed. The portal vein was occluded and infiltrated by cancer and therefore was resected and not reconstructed. After a slow recovery, the patient developed hemorrhage at the gastrojejunal anastomosis, which was controlled by fibrin injection. Within a few days, she presented with signs of sepsis, and blood cultures yielded Clostridium perfringens, Streptococcus oralis, Staphylococcus aureus, and Candida albicans. The source of the sepsis proved to be a 9-cm liver abscess, which was drained; cultures grew C. perfringens, Hafnia alvei, and Enterobacter cloacae. Despite antibiotic treatment, the patient died from sepsis and multiorgan failure 27 days after pancreatic surgery. CONCLUSION: Such rare infections can follow pancreatic resection with neoadjuvant radiochemotherapy. Clostridium perfringens-associated liver abscess maintains a high mortality rate.

Recurrent appendicitis after conservative management of perityphlitic abscess: report of two cases.

We report on two cases of recurrent appendicitis after conservative management consisting of antibiotics and percutaneous drainage of perityphlitic abscess. The first patient presented 13 years after acute appendicitis with a perityphlitic abscess that was treated operatively. This patient refused to undergo interval appendectomy after the initial event. The second patient with appendicitis and perityphlitic abscess was equally managed conservatively initially but presented with reperforated appendicitis and diffuse peritonitis 1 week before scheduled interval appendectomy and also had to undergo surgery. Based on our experience with these two cases, we conclude that interval appendectomy after the recommended period of 6-12 weeks might not be appropriate and may better be managed by performing it in the case of a recurrence.

Postoperative morbidity following chemoradiation for locally advanced low rectal cancer.

BACKGROUND: Postoperative morbidity remains a significant clinical problem and may alter long-term outcome particularly after neoadjuvant chemoradiation in patients with locally advanced low rectal cancer. The aim of the present study was to identify a potential long-term effect of postoperative morbidity. METHODS: Analysis of prospectively collected data of 90 consecutive patients who underwent neoadjuvant chemoradiation and curative mesorectal excision for locally advanced (cT3/4, Nx, M0/1) adenocarcinoma of the mid and lower third of the rectum during a 7-year period (1996-2002). RESULTS: Major postoperative complications occurred in 17.8% and minor complications in 26.6% of patients. Hospital mortality and 30-day mortality was 0%. Infectious complications were seen in 34.5%. The leading causes of infectious complications were anastomotic leakage and perineal wound infection. Postoperative morbidity was statistically significantly associated with gender (P < 0.05), pre-therapeutic haemoglobin level (P < 0.05), ASA score (P < 0.05), hospitalisation (P < 0.001) and clinical long-time course (P < 0.01). Moreover, early postoperative morbidity was proven as an independent prognostic factor concerning disease-free (P < 0.05) and overall survival (P < 0.05). CONCLUSION: Early postoperative morbidity in patients with preoperative chemoradiation due to locally advanced low rectal cancer is demonstrated as an independent prognosticator. Gender, pre-therapeutic haemoglobin level and ASA score indicate patients at risk for early postoperative complications and may therefore serve as predictive features.

Zygomycosis and other rare filamentous fungal infections in solid organ transplant recipients.

Fungi cause severe infections in solid organ transplant (SOT) recipients. Recently, a shift towards non-Aspergillus filamentous fungal infections (nAFFI) was noticed. In a series of 2878 SOTs (kidney, pancreas, islets, liver, heart, lung, and bowel) performed between January 1995 and December 2006 at the Innsbruck medical university, eleven cases of nAFFI were diagnosed. The encountered species included Zygomyzetes (n = 8), and Alternaria alternate, Pseudallescheria boydii, Trichoderma spp. (one each); there were three liver and three heart, one intestinal, pancreas, lung, bilateral forearm and renal recipient each. Five patients died from nAFFI (zygomycosis: 4, Pseudallerichia boydii: 1); four were diagnosed postmortem. In five cases infection was surgically treated in combination with antifungals. Risk factors for nAFFI were renal failure (73%) and intensified immunosuppression (73%); two cases were associated with post-transplant lymphoproliferative disorder, one with graft versus host disease. An increase in the incidence of nAFFI was observed parallel to introduction of caspofungin and voriconazole (three cases until 12/2003, seven cases thereafter). NAFFI are increasingly found in SOT recipients. If diagnosed in time, the outcome seems acceptable. Intensified immunosuppression and exposure to antifungals not active against zygomycetes may be risk factors. Surgical therapy may play an important role in these infections.

Solid apocrine carcinoma of the skin: report of a rare adnexal neoplasm mimicking lobular breast carcinoma.

The so called 'sweat gland carcinoma' is a rare skin malignancy. The differentiation between apocrine and eccrine neoplasms remains difficult. Skin tumors of the axilla are often suspected to be metastasis of other neoplasms in particular breast cancer. A 71-year-old man presented with a morphea-like plaque of the right axilla which in punch biopsy was first suspected as metastasis of primary lobular breast carcinoma. After further clinical and laboratory work up including immunohistochemistry the original diagnosis of a breast cancer had to be changed to solid apocrine carcinoma of the skin. Wide excision with en-bloc axillary lymph node dissection was performed. Final tumor stage was pT2 N0 M0 (V0 L0). No adjuvant treatment was necessary, and there is no evidence of disease after 3 years. Solid apocrine carcinoma of the skin is a rare variant with apocrine differentiation. A survey of the stereotypical presentation of this lesion and a comparison with lobular breast carcinoma and other types of apocrine carcinoma of the skin is given.

Enterocolitis due to simultaneous infection with rotavirus and Clostridium difficile in adult and pediatric solid organ transplantation.

Diarrhea is a well-known complication of immunosuppression but is also frequently caused by pathogens such as Clostridium difficile (CD) and rotavirus (RV). Three adult and five pediatric solid organ recipients (SORs) developed diarrhea with simultaneous identification of CD and RV. Rotavirus was identified using an immunochromatografic- or enzyme-linked immunosorbent assay; CD was identified using a rapid immunoassay or enzyme immunoassay. One adult renal, one adult kidney-pancreas, one adult liver, and five pediatric liver recipients were affected. Onset of RV/CD infection ranged from 2 weeks to 4 years posttransplant. All patients presented with enterocolitis causing significant fluid and electrolyte loss. In adults, CD was treated with metronidazole and in children with oral vancomycin. RV infection was treated with fluid/electrolyte replacement. During diarrhea, a significant rise in tacrolimus serum level was noted. All patients cleared CD. One child developed recurrent episodes of RV infection and died from bacterial sepsis; the renal recipient died 6 months posttransplant from myocardial infarction. The remaining six patients are currently alive with well-functioning grafts. Simultaneous infection with CD and RV may lead to severe diarrhea in SORs. Both pathogens should be considered in SOR presenting with diarrhea.

Laparoscopically implanted gastric pacemaker after kidney-pancreas transplantation: treatment of morbid obesity and diabetic gastroparesis.

Combined kidney-pancreas transplantation is the treatment of choice for end-stage diabetic nephropathy. Weight gain post-transplant increases the risk for post-transplant complications and death due to cardiovascular events. Gastric pacemakers have been used for therapy of diabetic gastropathy and for the treatment of moderate morbid obesity. We report a patient who experienced significant weight gain following successful kidney-pancreas transplantation and was thereafter successfully treated for diabetic gastroparesis and morbid obesity by use of a laparoscopically implanted gastric pacemaker.

Experience with the use of piperacillin-tazobactam in pediatric non-renal solid organ transplantation.

Bacterial infection remains a major problem after solid organ transplantation (SOT), especially in children. Piperacillin-tazobactam (Pip-Tazo) is a beta-lactam-antibiotic combination with a broad spectrum of activity including gram-positive cocci as well as gram-negative rods, non-fermentative and anaerobic bacteria. The aim of this retrospective study was to critically review our experience with Pip-Tazo as perioperative prophylactic agent in pediatric non-renal SOT. Between 1993 and 2003 Pip-Tazo was used as initial perioperative prophylaxis in 45 pediatric patients who underwent a total of 49 transplants (36 liver-, seven cardiac-, two lung-, and four small bowel-) at our department. Median age of the children was 7.9 (range 0.5-18.1) years. A total of 34 rejection episodes following 27 transplants were diagnosed. During first hospitalization 44 infectious episodes were observed. Bacteria were responsible for 22 episodes including sepsis (n = 10), pneumonia (n = 5), wound infection (n = 4), urinary tract infection (n = 1), and clostridial colitis (n = 2). The isolated organisms were gram-positive cocci (n = 12), gram-negative rods (n = 3), non-fermentative bacilli (n = 4), and anaerobes (n = 3). Ten episodes were caused by Pip-Tazo resistant bacteria. Twenty-one of these infections were observed following antirejection therapy with pulse steroids. At later time points nine infectious episodes were successfully treated with a second course of Pip-Tazo. During follow up, eight patients died. Six deceased perioperatively: five from infection including aspergillosis (n = 4) and Pneumocystis jiroveci pneumonia (n = 1) and cerebrovascular bleeding (n = 1) and two children later on. At present 37 children (82%) are alive with well functioning graft after a median follow up of 39.2 (range 0.6-123.5) months. No severe side effects caused by Pip-Tazo were observed in any of the children. Pip-Tazo may be a suitable single agent for perioperative prophylaxis in pediatric non-renal solid organs recipients, however, a prospective comparative study is needed to make final conclusions.

Group milleri streptococci: significant pathogens in solid organ recipients.

Group milleri streptococci (GMS) comprise a heterogeneous group of streptococci including the species intermedius, constellatus and anginosus. They may cause chronic intra-abdominal and intrathoracic abscesses, which are difficult to treat. This is a retrospective analysis including 45 transplant recipients in whom GMS were isolated. The epidemiology, clinical significance and the impact on the outcome in all transplant patients with infections caused by GMS during a 4-year period (2001-2004) was evaluated. The 45 solid organ recipients (88 isolates) included 34 liver-, four kidney/pancreas-, one kidney-, two small bowel-, three combined liver/kidney- and one combined kidney/small bowel transplant recipient. In 42 cases GMS caused intra-abdominal infection, in two cases pleural empyema and in one case soft tissue infection. Only a single isolate of GMS was cultured from blood. In 54 of the 88 specimens (61%), which grew GMS, other pathogens were also isolated. GMS frequently caused recurrent cholangitis (n = 17) associated with anastomotic and nonanastomotic biliary strictures. These cases were managed by repeated stenting or surgical intervention and prolonged antibiotic therapy. No patient died directly related to GMS infection and all except one case responded to combined surgical/antibiotic treatment. One pancreas graft was lost because of erosion haemorrhage associated with an abscess. GMS were susceptible to penicillin G, carbapenems and clindamycin, whereas cephalosporins and quinolones showed intermediate activity or resistance in some cases, and GMS in general were found resistant to aminoglycosides. GMS may cause serious infections in transplant recipients which are difficult to treat. Their prevalence in transplant surgical site infections thus far may have been underestimated.

Rothia dentocariosa sepsis in a pediatric renal transplant recipient having post-transplant lymphoproliferative disorders.

BACKGROUND: Rothia dentocariosa (RD) is a Gram-positive rod that colonizes the human oral cavity and can cause infective endocarditis. RESULT: We report on a six-yr-old boy who underwent renal transplantation for polycystic kidney disease at the age of eight months. He developed post-transplant lymphoproliferative disorders after four yr and progressive graft failure. Following chemotherapy, the patient presented with neutropenia and sepsis. RD was isolated from blood and treatment with piperacillin/tazobactam was initiated; however, the child died because of multiorgan failure. DISCUSSION: To the best of our knowledge, this is the first case of RD sepsis in a pediatric solid organ transplant recipient.

Severe intra-abdominal infection due to Streptococcus Milleri following adjustable gastric banding.

BACKGROUND: Laparoscopic adjustable gastric banding represents a safe and effective bariatric surgical method. Nevertheless, complications such as intraabdominal infections are associated with high morbidity and mortality. CASE REPORT: A 50-year old morbidly obese female patient underwent adjustable gastric banding with the Swedish band (SAGB). After an uneventful postoperative follow-up of 2 years, she developed band infection due to colon microperforation during endoscopic polypectomy. As the causative microorgansim, Streptococcus Milleri was revealed. Band removal was required, and recovery was quite prolonged. CONCLUSION: Intra-abdominal infection with Streptococcus Milleri can cause severe and life-threatening disease. Therefore, early diagnosis and surgical intervention combined with body weight adapted antibiotic therapy for a sufficiently long period of time seems necessary. In patients with intra-abdominal implanted devices such as the SAGB who undergo endoscopic polypectomy, antibiotic prophylaxis should therefore be considered.

Severe endocarditis in transplant recipients--an epidemiologic study.

Infective endocarditis (IE) is reported with an incidence of 6/100,000 inhabitants in the general population. Even though immunosuppression predisposes to systemic infection, reports regarding IE after solid organ transplantation (SOT) are sparse. From 1989 to 2004, 2556 patients underwent SOT at the University Hospital Innsbruck. During this period, 27 transplant recipients were diagnosed IE. Nine patients (33.3%) were diagnosed at autopsy, eight patients (29.6%) were cured by antibiotic treatment and 10 patients (37.1%) underwent surgery. Overall mortality was 44.4% (12 patients). Staphylococcus was the predominant microorganism in 16 cases (59.3%), fungal infection was present in four patients (14.8%). Incidence of IE was 1% (95% CI: 0.67-1.49), indicating a 171-fold risk compared with the overall population. IE after SOT constitutes a significant problem and is associated with an excessive high mortality. Alertness to this condition is indicated, as we might diagnose more cases of IE in the future.

Listeria meningitis in transplant recipients.

INTRODUCTION: Meningitis is a rare complication following organ and stem-cell transplantation and can be caused by a variety of microorganisms. AIM: To retrospectively review the clinical course and outcome of five cases of listeriosis in four organ recipients and one stem-cell recipient during a seven-year period. PATIENTS AND METHODS: Patient records for more than 3500 patients undergoing organ or stem-cell transplantation at the university hospital of Innsbruck during a 27-year period were evaluated. Standard immunosuppression consisted of calcineurin inhibitor-based triple drug therapy with or without ATG or IL2 receptor antagonist induction. RESULTS: The first case affected a 35-year-old woman who received an allogenic bone marrow transplant for advanced breast cancer. Cases two and three related to two male heart recipients. Cases four and five were diagnosed in one male and one female renal recipient. Listeria monocytogenes was isolated from blood in two cases and from cerebrospinal fluid in three. Treatment consisted of ampicillin in all cases with the addition of tobramycin (1), TMPS (1), meropenem (2) or imipenem/cilastatin (1). The deaths of two patients were directly related to L. monocytogenes. CONCLUSIONS: Although listeriosis is a rare complication following transplantation, this infection should be ruled out in individuals presenting with neurological symptoms and fever.