In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry.

PURPOSE: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration. METHODS: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments. RESULTS: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%). CONCLUSION: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.

Characteristics of viral pneumonia in the COVID-19 era: an update.

Influenza virus, rhinovirus, and adenovirus frequently cause viral pneumonia, an important cause of morbidity and mortality especially in the extreme ages of life. During the last two decades, three outbreaks of coronavirus-associated pneumonia, namely Severe Acute Respiratory Syndrome, Middle-East Respiratory Syndrome, and the ongoing Coronavirus Infectious Disease-2019 (COVID-19) were reported. The rate of diagnosis of viral pneumonia is increasingly approaching 60% among children identified as having community-acquired pneumonia (CAP). Clinical presentation ranges from mild to severe pneumonitis complicated by respiratory failure in severe cases. The most vulnerable patients, the elderly and those living with cancer, report a relevant mortality rate. No clinical characteristics can be useful to conclusively distinguish the different etiology of viral pneumonia. However, accessory symptoms, such as anosmia or ageusia together with respiratory symptoms suggest COVID-19. An etiologic-based treatment of viral pneumonia is possible in a small percentage of cases only. Neuraminidase inhibitors have been proven to reduce the need for ventilatory support and mortality rate while only a few data support the large-scale use of other antivirals. A low-middle dose of dexamethasone and heparin seems to be effective in COVID-19 patients, but data regarding their possible efficacy in viral pneumonia caused by other viruses are conflicting. In conclusion, viral pneumonia is a relevant cause of CAP, whose interest is increasing due to the current COVID-19 outbreak. To set up a therapeutic approach is difficult because of the low number of active molecules and the conflicting data bearing supportive treatments such as steroids.

Oral Therapy, Microbiological Findings, and Comorbidity Influence the Outcome of Prosthetic Joint Infections Undergoing 2-Stage Exchange.

BACKGROUND: The aim of the present study was to investigate potential predictive factors of an unfavorable outcome in patients with prosthetic joint infection (PJI) undergoing 2-stage exchange. METHODS: Patients with PJI undergoing 2-stage exchange and observed over a 5-year period (2009-2013) were included. Cure was defined by the disappearance of infection after a 96-week follow-up period. Statistical analysis was performed using the Mann-Whitney U test, the Fisher exact test, and the multivariate analysis. RESULTS: One-hundred twenty-two patients with PJI were included (median age, 69 years [range, 36-80 years]; 48% males, 47 hip PJI, and 75 knee PJI). Known comorbidities related to an increased risk of infection were reported in 43 patients (35%). Microbiological definition was obtained in 101 (83%) patients, and Staphylococcus aureus was isolated in 44 (36%) patients. Coagulase-negative staphylococci were isolated in 41 (34%) patients. A favorable outcome was obtained in 102 of 122 patients (84%). After univariate analysis, bacterial growth from operative specimens (P = .007), growth of Gram-positive bacteria (P < .001), use of oral therapy (P = .01), and absence of known comorbidities (P = .02) were associated with favorable outcome. Administration of rifampin (P = .99) and results of blood analysis were not predictive of outcome. After multivariate analysis was applied, infection sustained by Gram-positive bacteria, administration of oral antibiotics, and absence of known comorbidities frequently resulted in favorable outcome. CONCLUSION: A favorable outcome in patients with PJI undergoing 2-stage procedure was associated with an infection sustained by Gram-positive bacteria, absence of known comorbidities, and administration of oral therapy. Therefore, failure rate can be reduced with appropriate treatment choices.

Deep tissue biopsy vs. superficial swab culture, including microbial loading determination, in the microbiological assessment of Skin and Soft Tissue Infections (SSTIs).

Thirty-two patients affected by SSTIs including DFIs were enrolled between 2013 and 2014. Superficial swab was obtained before and after cleansing with sterile saline, and after ultrasonic debridement; deep tissue biopsy was obtained from ulcer base. Samples were diluted with 1 mL of saline, serial 10-fold dilutions to 10-6 were made and 50 µL of each dilution was plated onto appropriate media. Bacteria were identified by Vitek II system. Microbial load was expressed as CFU/mL. Statistical analysis was performed by χ2. Incidence of Gram positives was higher than Gram negatives (S. aureus and P. aeruginosa being the most frequent); concordance (same bacteria isolated before and after debridement) never exceeded 60%. Ultrasonic debridement significantly reduced bacterial load or even suppressed bacterial growth. While reliability of superficial swab is poor for microbiological diagnosis of SSTIs, swabbing after ultrasonic debridement and biopsy of the ulcer base may be equally reliable.

Diagnostic and therapeutic appropriateness in bone and joint infections: results of a national survey.

The impact of infectious diseases (ID) specialist consultation in the management of many types of bacterial infections has been fully demonstrated but not for bone and joint infections (BJIs). Nineteen ID Italian centres collected of data from June 2009 to May 2012. Italian guidelines (2009) were used to determine the appropriateness of the diagnostic and therapeutic process of BJIs before and after consulting an ID specialist. Data on 311 patients were collected: 111 cases of prosthetic joint infection, 99 osteomyelitis, 64 spondylodiscitis and 37 fixation device infection. A significant increase of microbiological investigations, imaging techniques and blood inflammation markers were noted after consulting the ID specialist. Moreover, inappropriateness of treatment duration, dosage, and number of administrations significantly decreased after consultation. Infectious disease specialist intervention in the management of BJIs significantly increases the appropriateness both in performing instrumental and laboratory analysis, but especially in determining the correct therapy.

Bacterial Epidemiology and Antimicrobial Resistance in the Surgery Wards of a Large Teaching Hospital in Southern Italy.

OBJECTIVES: Surgical infections represent an increasingly important problem for the National Health System. In this study we retrospectively evaluated the bacterial epidemiology and antimicrobial susceptibility of the microorganisms concerned as well as the utilization of antibiotics in the General and Emergency Surgery wards of a large teaching hospital in southern Italy in the period 2011-2013. METHODS: Data concerning non-duplicate bacterial isolates and antimicrobial susceptibility were retrieved from the Vitek 2 database. The pharmacy provided data about the consumption of antibiotics in the above reported wards. Chi-square or Fisher's exact test were used. RESULTS: In all, 94 Gram-negative were isolated in 2011, 77 in 2012, and 125 in 2013, Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa always being the most frequently isolated microorganisms. A. baumannii showed high rates of resistance to carbapenems (with values of 100% in 2011 and 2012) and low rates of resistance to tigecycline, colistin and amikacin. In the same years, there were respectively 105, 93, and 165 Gram-positive isolated. The rate of MRSA isolates ranged from 66% to 75% during the study period. CONCLUSIONS: Our results show no significant increase in antimicrobial resistance over the period in question, and a higher rate of both MRSA isolates and resistance to carbapenems in A. baumannii compared with other European data.

Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient. A rare case report and literature review.

Sphingomonas paucimobilis occurs widely both in natural and nosocomial environments, including hospital water systems, respiratory therapy equipment, and laboratory instruments. It is an opportunistic pathogen that rarely causes infections in humans. Among S. paucimobilis nosocomial infections, osteomyelitis is particularly rare. Almost all infections occur in patients with comorbidities such as malignancy, immunosuppressant therapy, diabetes mellitus and acquired immunodeficiency syndrome. We present the first case of Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient and include updated literature concerning infections by this microorganism.

BRAF (V600E) associates with cytoplasmatic localization of p27kip1 and higher cytokeratin 19 expression in papillary thyroid carcinoma.

The genetic alterations are responsible for the altered protein expression in tumors. The knowledge of the link between the altered protein expression and genetic alterations may provide potentially important biological and clinical information. In this study, the expression of some protein markers (Gal-3, p21Kip1, CK19) known to be associated to the papillary thyroid carcinoma (PTC) was assessed in a series of surgical samples by immunohistochemistry, and the association between expression of these markers and the BRAF (V600E) mutation was investigated. Gal-3 positive staining was evident in 26 % of benign nodules. The BRAF (V600E) mutation and Gal-3 expression, were found in 55.5 and 87 % of PTC respectively, and were unlinked. The expression of CK19 in benign nodules was weak and limited to scattered follicular cells. Diffuse cytoplasmatic expression of CK19 was present in malignant tumors in a variable percentage of cells. A higher percentage of CK19 expressing cells was associated with BRAF (V600E) (P ≤ 0.001). All benign nodules displayed nuclear p27kip1 in more than 15 % of the cells. Twenty-nine PTC showed a cytoplasmatic staining with negative nuclei. PTC with cytoplasmatic or 0-5 % of cells with nuclear staining, 6-15 % or >15 % of cells with nuclear staining were 72 (66.7 %), 24 (22.2 %), and 12 (11.1 %) respectively. In BRAF (V600E) positive tumors, the cytoplasmatic localization of p27kip1 was significantly more frequent (P = 0.024). In conclusion, we provide evidences that BRAF (V600E) is non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in PTC.

[Adjuvant treatment of diabetic foot]. / Trattamenti adiuvanti del piede diabetico.

A diabetic infected foot with erythema and fluctuation can suspect that the infection has passed the fascial compartmental, a condition that requires surgical drainage. Elective amputation may be considered for patients who have recurrent ulcers, irreversible loss of function or injuries that require long-term treatment in the hospital. If the diabetic infected foot appears ischemic it requires a treatment of revascularization. The outcome of revascularization is related with the extension of the damaged artery. The debridement removes the bacterial colonies, promotes granulation tissue and its reepithelialization, also facilitates the collection of samples for microbiological analyses. This procedure can be performed with the classic sharp instruments or with advanced autolytic dressings, maggots or ultrasonic equipment. The use of hyperbaric oxygen therapy in the treatment of infected diabetic foot is controversial because studies in this area are few and methodologically questionable. The same conclusion was reached also for the use of growth factors and skin substitutes.

Antibiotic prophylaxis in catheter-associated urinary infections.

This study aimed to assess the usefulness of antibiotic prophylaxis with Levofloxacin (LVFX) in short and mediumterm catheterisations. This study was developed to evaluate and confirm the effectiveness and need for prophylaxis in preventing catheter-associated UTIs, using LVFX at a dose of 250 mg administered orally to patients who had been subjected to short and medium-term urinary bladder catheterisation following surgery (3-14 days). The study was designed as a phase III study with parallel groups, multicentre, randomised, controlled with a placebo in three groups. The study was double-blind in treatment groups A and B and single-blind in group C. The study involved the recruitment of 120 patients, 40 for each treatment group. We show two types of results, one based on primary effectiveness variables and the other on the secondary effectiveness variables. The group treated with LVFX displayed a greater tendency toward the negativisation of bacteriuria and pyuria tests than that recorded for the placebo group, and was essentially comparable to that recorded for the group of patients treated with Ciprofloxacin. We can thus affirm that LVFX may be useful for preventing short and medium-term CAUTIs.

[Skin and soft tissue infections: classification and epidemiology]. / Infezioni della cute e dei tessuti molli: classificazione ed epidemiologia.

In the present review, authors take into consideration the classification and the epidemiology of the skin and soft tissue infections (SSTIs), a set of commonly observed pathologies, which can present different features, relatively to site and localization, clinical characteristics, and aetiological agent, their severity being related to the depth of the interested sites. Given the variable presentation of SSTIs, an assessment of their incidence and prevalence is difficult. In general, the incidence of SSTIs has increased due to the ageing of the general population, the increased number of critically ill patients, the increased number of immunocompromised patients (HIV, cancer and organ transplant patients) and the recent emergence of multi-drug resistant pathogens.

Prosthetic joint infections: microbiology, diagnosis, management and prevention.

Infections associated with prosthetic joints occur less frequently than aseptic failures but represent the most devastating complication, with high morbidity and substantial cost. The most important risk factors are co-morbidity and prior joint replacement (revision surgery). No single routinely used clinical or laboratory test has been shown to achieve ideal sensitivity, specificity and accuracy for the diagnosis of prosthetic joint infection (PJI). Therefore, only the sum of clinical signs and symptoms, blood tests, histopathology, radiography, bone scans and a microbiological work-up can provide an accurate diagnosis. Antimicrobial therapy must always be combined with the correct surgical treatment, which is chosen according to the duration of the infection and co-morbidities of the patient. This review will briefly discuss the microbiology, diagnosis, management and prevention of PJI.

[Management of severe bacterial infections and role of the infectious disease specialist: results of an interview-based survey]. / Gestione delle infezioni batteriche gravi e ruolo dell'infettivologo. Risultati di una indagine condotta a mezzo di intervista.

Ascertainment of SBIs plays a central role in their management, which can affect the prognosis, hopefully avoiding an inappropriate antibacterial therapy concerning choice, dosing, timing, duration and route of administration of antibiotics. Different aspects of SBI management were evaluated by interviewing doctors practising in ICU, Surgery and Haematology wards. In the period 16 June - 7 July 2003, 150 doctors, equally distributed by specialty and geographical location, experienced in the management of antibiotic therapy, were interviewed in order to acquire the following information: criteria adopted to define SBIs, presumed incidence, most frequent diagnosis, initial approach to antibiotic therapy (empirical or not, route of administration, mono- or combination therapy), ID consultation request. In most cases generic and empirical criteria are used to define SBI, generally associated to the presence of co-morbidities, the highest rates being reported in ICUs (35.1%) and Haematology (34.7%) wards. Pneumonia is the top reported SBI in all the wards, followed by sepsis in ICUs and Haematology, and by intrabdominal infections in Surgery. Antibiotic therapy is often empirical (~90%), often performed i.v. with antibiotics given in combination. Following treatment failure, which occurs on average in 35.5% of cases, ID consultation and microbiological investigation are required. ID consultation is required in 20.2%, 26.1% and 28.1% of cases by haematologists, surgeons and ICU specialists, respectively. SBIs frequently occur in all the wards where the interviews were conducted. Their management is generally empirical and either ID consultation or microbiological investigation is infrequently required especially as an initial approach. The use of appropriate guidelines and ID consultation, as proven in many controlled studies, could be efficacious in reducing the incidence of inappropriate therapies and increasing favourable outcome rates.

Ceftriaxone versus Other Antibiotics for Surgical Prophylaxis : A Meta-Analysis.

OBJECTIVE: To investigate possible differences in prophylaxis with ceftriaxone compared with other antimicrobial agents for surgical-site infections and remote infections such as respiratory tract infections (RTIs) and urinary tract infections (UTIs). METHODS: The efficacy of ceftriaxone was compared with that of other antibiotics in the perioperative prophylaxis of local (surgical wound) and remote (RTIs and UTIs) infections in a meta-analysis of randomised controlled trials published between 1984 and 2003. The analysis was based on a 2 x 2 contingency table with classification by treatment and number of infections obtained from individual studies. RESULTS: Evaluations were performed on 48 studies, for a total of 17 565 patients. Overall, 406 patients (4.8%) in the ceftriaxone group and 525 (6.3%) in the comparator group developed a surgical-site infection (log odds ratio [OR] -0.30 [CI -0.50 to -0.13]; p < 0.0001). RTIs were observed in 292 (6.01%) patients in the ceftriaxone group and in 369 (7.6%) patients in the comparator group, (log OR -0.30 [CI -0.55 to -0.09]; p = 0.0013). UTIs were reported for 2.2% of the ceftriaxone prophylaxis patients compared with 3.74% of the comparator group patients (log OR -0.54 [CI -1.18 to -0.16]; p < 0.0001). Overall, in clean surgery 195 (5.1%) and 234 (6.2%) patients developed a surgical site infection in the ceftriaxone and comparator groups, respectively (log OR -0.22 [CI -0.51 to 0.01]; p = 0.0476). RTIs were prevented for all but 1.57% of patients in the ceftriaxone group and 2.62% of patients in the comparator group (p = 0.01) in clean surgery, and for 9.54% of the ceftriaxone group versus 11.6% of the comparator group (p = 0.01) in clean-contaminated surgery. While results observed in clean surgery did not show statistically significant superiority of ceftriaxone in preventing UTI insurgence (log OR -0.21 [CI 0.0-0.65]; p = 0.7702), this was clearly shown in the clean-contaminated surgery. In fact, 4.47% of patients in the ceftriaxone group versus 7.52% of patients in the comparator group developed a UTI (log OR -0.56 [CI -1.25 to -0.16]; p < 0.0001). Adverse events were observed in a similar proportion in the ceftriaxone prophylaxis and the comparator groups (0.35% and 0.23%, respectively). Duration of prophylaxis did not influence outcome of infection. CONCLUSIONS: The meta-analysis showed that ceftriaxone is statistically superior to other antibiotics in preventing both local and remote postoperative infections.

[Multicentre survey of post-surgical infections in Campania (Italy)]. / Multicentre survey of post-surgical infections in Campania (Italy).

The aim of the study was to evaluate the incidence of post-surgical infections and to assess the way of managing antibiotic surgical prophylaxis. The survey was carried out by means of a questionnaire in order to obtain diverse information such as demographics, length of pre- and post-operative hospitalization, type of surgery, intervention duration, possible antibiotic prophylaxis and onset of post-surgical infections also monitored by post-discharge ambulatory controls. Four General Surgery and five Obstetrics and Gynaecology Departments in Campania (southern Italy) participated in the study, which was carried out in the period December 2001-January 2002. Overall, 410 questionnaires were collected referring to as many patients; antibiotic prophylaxis was performed in 385 (93.9%) patients. Antibiotic prophylaxis was generally managed not according to the general principles suggested by the international guidelines either for timing or for its duration or for the route of administration. Substantial differences were also noted in patient selection and antibiotic choice. Surgical site infections were recorded in 0.6% of patients undergoing clean surgery, in 5.3% of patients undergoing clean-contaminated surgery and in 3.2% of those undergoing contaminated surgery. Distant infections occurred in 1.8% and 6.5% in clean-contaminated and contaminated surgery, respectively. The results of the present study suggest the need of a continuous and accurate monitoring of post-surgical infections and the need to adopt appropriate guidelines to improve the management of surgical prophylaxis.

Macrolide-resistance genes in clinical isolates of Streptococcus pyogenes.

Macrolide-resistance genes were investigated in 103 macrolide-resistant strains of Streptococcus pyogenes, isolated from children with pharyngotonsillitis. The presence of mef(A), erm(B), and erm(TR) genes was detected by PCR. mef(A) was found in 48 out of 103 (46.6%) strains, whereas erm(B) was detected in 43 isolates (41.7%). All mef(A) strains showed a typical M phenotype (resistance to 14- and 15-membered macrolides, and sensitivity to lincosamides and streptogramin B), whereas erm(B) strains had the MLSB phenotype (resistance to macrolides, lincosamides, and streptogramin B antibiotics). erm(TR) was found in 10 strains, always together with other resistance genes. In seven cases erm(TR) was associated with erm(B), and three cases with mef(A). In two isolates with the M phenotype (1.9%), it was not possible to detect the presence of any of the three macrolide resistance genes tested. Inducible resistance to macrolides was shown for 24 out of the 53 MLSB strains. Analysis of macrorestriction fragment patterns by pulsed-field gel electrophoresis showed that erythromycin-resistant S. pyogenes are polyclonal, however each phenotype, MLSB and M, formed essentially homogeneous groups.

[Antibiotic prophylaxis in surgery: news and controversies]. / Profilassi antibiotica in chirurgia: attualità e controversie.

Preoperative administration of antibiotics to prevent possible post-surgical infections represents a cornerstone of modern medicine. Although the general principles of surgical prophylaxis have been quite clearly defined during the last few decades, advenaces in surgical techniques, the changes in bacterial ecology in hospital, the spread of bacterial resistance and the substantial increase in the surgical population at risk, suggest that several aspects of surgical prophylaxis should be reviewed and new controlled studies should be carried on. The American guidelines for surgical prophylaxis, worked out recently by the CDC, have not modified their general structure, and have strongly influenced the protocols and the prescriptive behaviour of other countries, including Italy. The following points suggest that these guidelines are probably no longer adeguate for the situation in question: evidence from several sources would extend the advisability of antibiotic prophylaxis to other clean surgeries; the current classification of surgical procedures does not consider the "new" population of risk patients; the duration of prophylaxis and its role in preventing post-surgical infections "at a distance" infections has not been carefully defined; the evolution of bacterial epidemiology and bacterial resistance and the contemporary availability of new antibiotics has moved the fear of a post-antibiotic era In the clinical practice, according to these considerations and whilst awaiting the results of new clinical trials, in some cases and for some at risk patients it would appear justified to use third generation cephalosporins and especially ceftriaxone that, because of its peculiar pharmacokinetcs characteristics, guarantees with a single dose the same efficacy of three doses of other cephalosporins.