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Staphylococcus aureus is still an important problem in clinical and therapeutic area, worldwide. In Italy, in recent years, methicillin resistance remained stable, yet considerably high, the percentage of strains of MRSA being around 40%. It was deemed interesting and timely to carry out a consensus conference using the RAND/UCLA method to collect the opinion of a group of experts in infectious diseases on the role of glycopeptides in the management of MRSA infections within several clinical scenarios and namely in pneumonia, bacteremia and endocarditis, joint replacement infections, skin and soft tissue infections, diabetic foot, abdominal infections and central nervous system infections. The scenarios proposed by the Scientific Committee have been validated by a group of experts in infectious diseases and then voted in three meetings of infectious disease specialists. The results obtained on each individual condition were analyzed and therapeutic recommendations on each of these were released.

Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges. Fourteen members of the Italian Society of Infectious Diseases, after a careful review of the most recent literature using Medline database and their own clinical experience, updated a previous paper published in 2011 by preparing a draught manuscript of the statements. The manuscript was successively reviewed by all members and ultimately re-formulated the present manuscript during a full day consensus meeting. The microbiological and clinical aspects together with diagnostic features were considered for necrotizing and not necrotizing SSTIs in the light of the most recent guidelines and evidences published in the last five years. The antimicrobial therapy was considered as well - both empirical and targeted to methicillin-resistant Staphylococcus aureus and/or other pathogens, also taking into account the epidemiological and bacterial resistance data and the availability of new antibacterial agents.

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.

Background: Daptomycin pharmacokinetics has not been extensively studied in patients undergoing continuous renal replacement therapy (CRRT)., Methods: The aim of the study was to collect pharmacokinetics and clinical data of patients undergoing CRRT and receiving daptomycin therapy. Daptomycin was measured using an isocratic high-performance liquid chromatography technique., Results: Three patients with bloodstream infection underwent CVVHD and three CVVHDF. CVVHDF patients had significantly lower mean AUC(0-24) and C(max) values. A significant decrease in plasma levels was observed in a CVVHDF patient using 'high cut-off' hemofilters., Conclusion: Increasing doses of daptomycin should be considered in critical patients, especially those undergoing CVVHDF.

Invasive pulmonary aspergillosis (IPA) is one of the major causes of morbidity and mortality in severely immunocompromised patients, but recently several authors have reported the occurrence of IPA in liver cirrhosis, chronic obstructive pulmonary disease (COPD) patients, most of whom, but not all, were receiving steroid treatment, with a very high mortality rate. The detection of galactomannan performed in respiratory specimens is a new valuable test for the diagnosis of probable IPA, even in non-neutropenic high risk patients. Since the frequency and clinical impact of IPA in non-hematologic patients is not well known, it seemed rational to us to attempt a prospective study evaluating all patients hospitalized in a university hospital for whom an infectious Diseases consultation was required. This 14-month survey in our hospital, using recently recommended diagnostic criteria, seems to suggest an emerging role of IPA in these patients who may have a higher mortality rate than their neutropenic peers, and provides preliminary evidence that early diagnosis and prompt initiation of antifungal therapy may improve the ultimate outcome of their IPA.

Skin and soft-tissue infections (SSTIs) are among the most common bacterial infections, posing considerable diagnostic and therapeutic challenges and resulting in significant morbidity and mortality among patients as well as increased healthcare costs. eight members of the SSTI working group of the Italian Society of infectious Diseases prepared a draft of the statements, grading the quality of each piece of evidence after a careful review of the current literature using MEDLINE database and their own clinical experience. Statements were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America (IDSA). The manuscript was successively reviewed by seven members of the SSTI working group of the international Society of Chemotherapy, and ultimately re-formulated by all e xperts. the microbiological and clinical aspects together with diagnostic features were considered for uncomplicated and complicated SSTIs. Antimicrobial therapy was considered as well -both empirical and targeted to methicillin-resistant Staphylococcus aureus (MRSA) and/or other main pathogens.

Candida species are the most common causes of invasive fungal infections in humans, producing infections that range from mucocutaneous disorders to invasive disease that can involve any organ. Here we present our clinical experience with anidulafungin for the treatment of documented nosocomial candidaemia. From february 2009 through January 2010 all patients with documented candidemia treated with anidulafungin in three medical centers in italy were reviewed. Demographics, clinical and microbiological data, and outcome were collected for each patient. Twenty-four patients were included in the study. most patients had a central venous catheter (CVC) or a port-a-cath (100%), had a history of recent surgery (87.5%), or were receiving total parenteral nutrition (79%), broad spectrum antibiotics (83%), steroids or chemotherapy (45.8%). C. albicans (54%) was the most commonly isolated pathogen. CVC was the source of candidemia in 79% of cases. Six patients (25%) developed severe sepsis or septic shock, and five patients had unfavorable outcomes, with an overall mortality rate of 20%. No patients experienced side effects related to anidulafungin therapy. Anidulafungin was effective in the treatment of patients with documented candidemia arising from different sites, and no significant side effects were observed.

Carbapenem-resistant Acinetobacter baumannii was isolated from 15 colonized or infected patients (carriers) between April and July 2004, in a teaching hospital ICU in Rome, Italy. All isolated strains were susceptible only to gentamicin, ampicillin-sulbactam and colistin and displayed the same Random Amplified Polymorphic DNA (RAPD) 1 pattern. Twelve out of 15 strains were susceptible to tigecycline, whereas the remaining three showed intermediate susceptibility. Although infection control measures were reinforced and carriers isolated in separate rooms, A. baumannii transmission continued. Therefore, finally A. baumannii carriers were moved to another available subintensive unit, which was re-equipped, and cared for by dedicated personnel, whereas only the non infected/colonized patients remained in the ICU. This study shows that during an outbreak by multiresistant A. baumannii it may be indispensable to geographically isolate not only patients but also dedicated staff.

Staphylococcus haemolyticus strains (n=20), responsible of blood stream infections, were consecutively isolated from patients hospitalized in two different wards at high risk of infection. Strains displayed high rate of resistance to oxacillin (90%). All strains but two with decreased susceptibility (MIC = 4 microg/mL), were sensitive to vancomycin. Ten strains were resistant to teicoplanin. Among the strains susceptible to glycopeptides, three displayed heteroresistance to vancomycin and seven to teicoplanin, when tested by Etest technique with 2 x McFarland inoculum. Biochemical reactions allowed to assign strains to eight biotypes, with 11 strains clustering under two main biotype A and biotype B. Pulsed-field-gel-electrophoresis (PFGE) identified 11 different PFGE-types. Seven strains grouping under the major PFGE-type 1 and three strains clustering in PFGE-type 2, closely correlated to biotype A and biotype B respectively. Seven teicoplanin-resistant isolates clustered in the PFGE-type 1, two in the PFGE-type 2 and one in PFGE-type 5. Therefore, teicoplanin-resistant strains were biochemically and genetically related and clonally distributed, despite different clones of S. haemolyticus circulated in the units during the study period.

In spite of the adoption of third generation cephalosporin restriction policies, two independent outbreaks by Extended Spectrum Beta-Lactamase (ESBL)-producing Klebsiella pneumoniae occurred in two different wards (Neonatal Intensive Care Unit, NICU and Neurosurgery) of a teaching hospital in Rome, Italy. In the former 19 infected neonates were reported, whereas in the latter there were 10 infected patients. In both wards no differences were observed in the mortality rates in periods of outbreak and those with no outbreak. Molecular typing on a total of 19 isolated strains was carried out and restriction patterns were compared. The PFGE showed that nine isolates responsible for infection in the NICU were all included in three closely related clusters. In Neurosurgery nine strains out of ten were strictly related and part of an outbreak occurring between August-December 2003, while one isolate was temporarily (February 2003) and genetically (seven band differences) unrelated to the outbreak strains. When ESBL producing K. pneumoniae clusters from the two wards (NICU vs Neurosurgery) were compared, they appeared to be completely different both for their genotype pattern and plasmid type or presence, thus demonstrating cross transmission by two different genotypes.

Although Staphylococcus haemolyticus (SH) represents an emerging etiology of methicillin-resistant (MR) coagulase-negative staphylococcal nosocomial bacteremia, little is known of clinical significance of this infection. Thus, we performed case-control retrospective comparative analysis of MRSH bacteremias (MRSHB), methicillin-resistant S. epidermidis bacteremias (MRSEB), and methicillin-resistant S. aureus bacteremias (MRSAB) in patients with hematologic malignancies. Most patients in the three groups were neutropenic and had a central venous catheter (CVC) in place at the onset of bacteremia. However, MRSHB patients had a CVC in place prior to bacteremia for a time significantly more prolonged than MRSEB and MRSAB ones (p<0.05). Severe sepsis or septic shock were more common in patients with MRSAB as compared with MRSHB (p=0.02). Nosocomial attributable mortality rate was very low in the 3 study groups (0 to 5.4%) and only two patients developed metastatic infections. Overall, reduced susceptibility to teicoplanin was observed in 19 (47.5%) MRSH and in 4 (10%) MRSE isolates. Resistance to teicoplanin was observed in 6 isolates, all MRSH. Reduced susceptibility or resistance to vancomycin was observed in 2 isolates, both MRSH. All MRSA isolates were susceptible to the glycopeptides. Comparison between cases of bacteremia in patients with MRSH isolates with reduced susceptibility to teicoplanin and those with susceptible MRSH did not reveal significant differences in the clinical-microbiological response to teicoplanin therapy and outcome. Our results seem to suggest that MRSHB in hematologic patients is associated with low morbidity and mortality rates. MRSH frequently shows a reduced susceptibility to teicoplanin; however these in vitro data do not seem associated with an unfavorable clinical response to teicoplanin therapy for MRSHB in patients with hematologic malignancies.

We tested the in vitro bactericidal activity of moxifloxacin, a new 8-methoxyquinolone, alone and in combination with vancomycin or teicoplanin at different multiples of minimum inhibitory concentration (MIC) against 8 methicillin-ciprofloxacin-resistant Staphylococcus aureus (M-C-RSA) and 1 methicillin-ciprofloxacin susceptible S. aureus (M-C-SSA) recently isolated from device-associated infections unresponsive to or relapsing after glycopeptide therapy, despite device removal. MICs of vancomycin ranged from 1 to 4 microg/ml, MICs of teicoplanin ranged from 2 to 8 microg/ml; MICs of moxifloxacin were always 2 microg/ml against M-C-RSA isolates and 0.125 microg/ml against the M-C-SSA isolate. The 9 strains resulted tolerant when tested for vancomycin, teicoplanin, and moxifloxacin used alone at 2 x MIC. In all cases the combination of moxifloxacin and teicoplanin or vancomycin appeared to be bactericidal already at MIC concentration for glycopeptides plus 0.5 x MIC concentration for moxifloxacin. If these results are confirmed in vivo in animal experiments, the combination of moxifloxacin with glycopeptides might be useful for treating device-associated infections, and in preventing the frightening phenomenon of increasing MICs for glycopeptides.

The conventional therapeutic approach to bone infection associated with osteosynthesis is based on the idea that microbial eradication is most readily achieved by removal of the foreign material together with adequate antimicrobial therapy. This strategy usually requires implantation of external fixation devices with additional discomfort to the patient. We report our experience with conservative medical and antimicrobial therapy without removal of the osteosynthesis until adequate bone callus deposition is documented by bone radiography scan. Twenty patients with infections associated with intramedullary nailing (9 patients), screws and plate (9 patients) or screws (2 patients) were treated between 1995 to 2000. Osteosynthesis implantation sites were tibia (7 patients), femur (6 patients), femur and tibia (1 patient), humerus (1 patient), others (5 patients). Diagnosis of infection was based on clinical-microbiological evidence and confirmed by 99Tc-labeled leukocyte scan studies. Offending pathogens were Staphylococcus aureus 17 cases, Staphylococcus aureus + Escherichia coli, Staphylococcus epidermidis, unknown, 1 case each. Most infections were initially treated with intravenous or intramuscular teicoplanin +/- ciprofloxacin or rifampin followed by oral antimicrobial therapy usually with ciprofloxacin or minocycline plus rifampin. Mean duration of antimicrobial therapy was 27.7 weeks (range 12-64 weeks). All patients (100%) were cured, and none complained of side-effects requiring antibiotic therapy discontinuation. We conclude that conservative medical therapy is feasible for osteosynthesis-associated bone infection.

We recently observed (February 1999) a 68-year old patient with endocarditis on a prosthetic biologic valve caused by a vancomycin-resistant Enterococcus faecalis. Broth dilution tests showed susceptibility to ampicillin (MIC=0.5 microg/ml), no high resistance to aminoglycosides (MIC for gentamicin <500 microg/ml) and resistance to vancomycin (MIC >256 microg/ml) and teicoplanin (MIC >16 microg/ml). A PCR assay detected vanA gene in this strain. A transthoracic echocardiogram did not show valvular vegetations. A possible endocarditis was diagnosed and the patient received ampicillin for 8 weeks and gentamicin for 6 weeks. The patient remained afebrile after a 4-month follow-up when he underwent surgical replacement of the dysfunctional bioprosthetic valve. Mitral valve was sterile on culture, but histology confirmed the diagnosis of previous endocarditis. This is the third case of endocarditis caused by vancomycin-resistant E. faecalis reported to date.

A 56-year old man with non-Hodgkin's lymphoma and biliary tract endoprosthesis, developed chronic bacteremia caused by Enterococcus faecalis with high-level resistance to gentamicin and streptomycin. The sources of bacteremia were a device-associated biliary tract infection, a suppurative thrombophlebitis of the confluence of the superior mesenteric vein with the splenic vein as well as multiple liver and pancreatic abscesses. Despite antibiotic therapy and multiple drainages of abscesses, the patient died due to overwhelming infection.

Changes in antibiotic susceptibility was evaluated in 77 consecutive nosocomial clinical isolates of Staphylococcus aureus collected from 1986 to 1994 at the Umberto I Polyclinic of the University of Rome (63 isolates) and from 7 other Roman hospitals (14 isolates). Oxacillin resistance in these isolates increased from 39% during the 1980s to 69% during the 1990s. Significant increases in resistance to ciprofloxacin, clindamycin and rifampicin were observed among oxacillin-resistant strains. No resistance to glycopeptides was observed although both teicoplanin and vancomycin had slightly reduced antistaphylococcal activity.

Bacterial infection may be a life-threatening complication in the immunocompromised host, especially in the face of profound and persistent granulocytopenia induced by cytotoxicity. Under these circumstances, antibiotic therapy is started on an empirical basis; however, knowledge of the antibiotic susceptibilities of the offending pathogen may represent a useful guide for therapy adjustments in individuals who do not respond satisfactorily to initial antibiotics. Careful antimicrobial susceptibility testing may also represent the first step of epidemiology investigations of nosocomial outbreaks; moreover, knowledge of antibiotic susceptibility patterns of the prevalent pathogens in certain institutions may help clinicians to formulate empiric antimicrobial treatments for febrile granulocytopenic patients. Careful quantitative studies involving determinations of the minimal inhibitory concentrations may help to evidence early, potentially clinically significant decreases in susceptibility to first choice antibiotics for important nosocomial pathogens. Relationship between appropriate or inappropriate treatment, based on in-vitro susceptibility testing results, and clinical outcome may help to define the clinical significance of some emerging bacterial pathogens in immunocompromised patients.

A retrospective, multicenter survey was performed to evaluate the frequency of vancomycin resistance among enterococcal blood isolates in Italian hospitals during 1993. Twenty-four laboratories, representing 21 cities, provided data on 177,623 blood cultures. Of 15,500 positive cultures, 778 (5%) yielded an Enterococcus. Of 362 evaluable cases of enterococcal bacteremia, a vancomycin resistant Enterococcus (VRE) was found in only 6 (1.6%). Based on these results, VRE bacteremia did not appear to be a major problem in Italian hospitals in 1993.

We identified 17 (20%) of 83 consecutive enterococcal isolates from hospitalized patients with documented infection as high-level ampicillin-resistant enterococci (ARE). Of these, 16 isolates were identified as Enterococcus faecium and 1 isolate as Enterococcus raffinosus. A case-control study found no significant differences with respect to underlying diseases, central venous catheterization, nosocomial acquisition of the infection and sites of infection. Patients with ARE infection were older and had a higher inhospital fatality rate than those with ampicillin-susceptible Enterococcus (ASE) infection. Hospitalization in a surgery service (usually for an abdominal procedure), prolonged hospital stay, prior treatment with antibiotics (in particular imipenem and metronidazole), were also more frequent among patients with ARE infection. ARE isolates were more frequently resistant to imipenem, ciprofloxacin and streptomycin than ASE isolates.

We reviewed our routine clinical laboratory records from January 1990 to March 1993 to evaluate the rate of oxacillin-resistance among nosocomial isolates of Staphylococcus aureus. Of 265 clinically significant isolates, 174 (65%) were oxacillin-resistant S. aureus (ORSA). Most of these strains were obtained from surgery patients and/or were isolated from surgical wounds. The isolations of S. aureus increased during the study period: 45 in 1990, 50 in 1991, 130 in 1992 and 40 in the first trimester of 1993. The annual rates of ORSA among S. aureus isolated varied from 62 to 68% through these years. Most ORSA isolates proved resistant to ciprofloxacin, gentamicin and rifampicin, and susceptible to vancomycin, netilmicin and cotrimoxazole. Based on these results, the need for a stringent application of infection control measures is outlined.

Seventy-five enterococci from infected (63 isolates) and colonized (12 isolates) patients hospitalized in various divisions of the Policlinico Umberto I, University of Rome, were in vitro studied for high-level resistance (HLR) to gentamicin (HLRG) and streptomycin (HLRS) with adoption of a standard broth dilution and an agar screen test. The employed procedures provided equal results for 100% of the 75 isolates. Of these, 21 (28%) showed HLRG and 43 (57%) HLRS. Combined HLRG and HLRS were found in 18 (24%) isolates, whereas HLRS or HLRG alone were found in 25 (33%) and 3 (4%) isolates respectively. It is concluded that HLR to aminoglycosides may represent a major problem in Italian institutions. Along with other established procedures, the agar screen test employed in the study may be used to detect this antibiotic resistance in enterococci.

Intravenous ciprofloxacin at a daily dosage of 400 mg divided in two doses was administered to 19 patients with severe infections caused by ciprofloxacin-susceptible bacteria. These infections included: 11 surgical would infections, 5 soft tissue infections, 2 respiratory tract infections, 1 urinary tract infection. The offending pathogens were: 8 coagulase-negative staphylococci, 3 Staphylococcus aureus, 3 Pseudomonas aeruginosa, 2 Proteus spp., 1 Escherichia coli, 1 Branhamella catarrhalis, 1 Klebsiella ozenae and 1 Serratia liquefaciens. Overall, 17 of 19 infections (89%) showed a satisfactory clinical response to trial therapy (15 cures and 2 improvements). Microbiological eradication was observed in 17 out of 20 isolated pathogens. Emergence of resistance to ciprofloxacin occurred in 1 coagulase-negative Staphylococcus and was associated with clinical failure. No side effects were observed. We conclude that intravenous ciprofloxacin may represent efficacious and safe therapy of severe infections; however close microbiological monitoring seems to be necessary to evaluate the emergence of resistance during quinolone therapy.

A total of 41 patients were randomly allocated to receive either cefotetan (total dose, 20 g) or clindamycin (total dose, 12 g) plus amikacin (total dose, 5 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, male to female ratio, stage of cancer, and the various types of surgery. No patient received radiotherapy or chemotherapy before surgery. The wound infection rate was 4% in the group of patients receiving cefotetan and 0% in the group receiving clindamycin plus amikacin. No major side effects were observed in either group. On the basis of this study a five-day perioperative course with cefotetan may be considered effective antimicrobial prophylaxis in patients undergoing major head and neck oncologic surgery.

Blastoschizomyces capitatus represents an emerging fungal pathogen in acute leukemia patients. The susceptibility to amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole of nine clinical isolates was evaluated. A specific medium (high resolution medium) was used for testing fluconazole. This agent and 5-fluorocytosine were at least four- to eight-fold more active than amphotericin B and ketoconazole against all isolates but one.

Despite progress in antimicrobial therapy, septicemia remains a major problem of modern medicine. The clinical features and outcome may vary in different clinical settings and in a single setting during the years. As an example, gram-negative bacilli have been the prevalent cause of fulminant septicemia in granulocytopenic patients during the seventies. Nowdays, the use of indwelling central venous catheters and/or quinolone prophylaxis have favored the emergence of coagulase-negative staphylococci as a major cause of septicemia in these patients. As a consequence, the optimal management of febrile episodes in granulocytopenic patients should include not only a combination of a broad spectrum betalactam plus an aminoglycoside to prevent early death from gram-negative septicemia, but also antistaphylococcal antibiotics in cases not improving after 72 hours. The clinical spectrum of infective endocarditis continues to evolve. Infection of the right heart valves that was rare until a few decades ago, is now a frequent cause of staphylococcal septicemia in intravenous drug addicts. Along with prosthetic valve infection, new clinical syndromes of nosocomial endocarditis are emerging. Infections of permanent central venous catheters, ventriculoatrial shunts or pace-maker leads may in fact cause right-sided infective endocarditis. Septicemia will continue to challenge physicians in the future.

The changes in coagulase-negative staphylococcal flora induced by cefamandole prophylaxis were compared with those induced by pefloxacin prophylaxis among patients undergoing heart valve surgery. Twenty-five patients (15 receiving cefamandole prophylaxis and 10 receiving pefloxacin prophylaxis) were included in the study. In the pefloxacin group, colonization rates in anterior nares and in chest skin or wound that were 60% and 50% respectively before surgery, became 50% and 20% respectively after surgery. In the cefamandole group, colonization rates in anterior nares and chest skin or wound were 53.3% and 60% respectively before surgery and became 53.3% and 40% respectively after surgery. Cefamandole did not appear to induce the emergence of oxacillin or pefloxacin resistant coagulase-negative staphylococcal colonization in any cultured site. On the other hand pefloxacin appeared somewhat more efficacious than cefamandole in eradicating staphylococcal flora of anterior nares and chest skin or wound. Pefloxacin and oxacillin resistant strains were found in the perianal area in 0% of patients before pefloxacin prophylaxis and in 70% of patients after pefloxacin prophylaxis. However, further studies are necessary to confirm the emergence of antibiotic resistant coagulase-negative staphylococci in the intestinal microflora after quinolone administration. The clinical implications of such apparently disturbing phenomenon remain to be evaluated.