Carlo Tascini

mcr-1.2, a New mcr Variant Carried on a Transferable Plasmid from a Colistin-Resistant KPC Carbapenemase-Producing Klebsiella pneumoniae Strain of Sequence Type 512.

ABSTRACT A novel mcr variant, named mcr-1.2, encoding a Gln3-to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512 Klebsiella pneumoniae isolate collected in Italy from a surveillance rectal swab from a leukemic child. The mcr-1.2 gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of mcr-1-bearing plasmids previously found in Escherichia coli and K. pneumoniae strains from geographically distant sites (Estonia, China, and South Africa).

Added Value of 99mTc-HMPAO–Labeled Leukocyte SPECT/CT in the Characterization and Management of Patients with Infectious Endocarditis

The clinical performance of the Duke Endocarditis Service criteria to establish the diagnosis of infectious endocarditis (IE) can be improved through functional imaging procedures such as radiolabeled leukocytes (99mTc-hexamethylpropyleneamine oxime [HMPAO]–labeled white blood cells [WBC]). Methods: We assessed the value of 99mTc-HMPAO-WBC scintigraphy including SPECT/CT acquisitions in a series of 131 consecutive patients with suspected IE. Patients with permanent cardiac devices were excluded. 99mTc-HMPAO-WBC scintigraphy results were correlated with transthoracic or transesophageal echocardiography, blood cultures, and the Duke criteria. Results: Scintigraphy was true-positive in 46 of 51 and false-negative in 5 of 51 cases (90% sensitivity, 94% negative predictive value, and 100% specificity and positive predictive value). No false-positive results were found, even in patients with early IE evaluated within the first 2 mo from the surgical procedure. In 24 of 51 patients with IE, we also found extracardiac uptake, indicating septic embolism in 21 of 24. Despite the fact that septic embolism was found in 11 of 18 cases of Duke-definite IE, most of the added value from the 99mTc-HMPAO-WBC scan for decision making was seen in patients in whom the Duke criteria yielded possible IE. The scan was particularly valuable in patients with negative or difficult-to-interpret echocardiographic findings because it correctly classified 11 of 88 of these patients as having IE. Furthermore, 3 patients were falsely positive at echocardiography but correctly negative at 99mTc-HMPAO-WBC scintigraphy: these patients had marantic vegetations. Conclusion: Our results demonstrate the ability of 99mTc-HMPAO-WBC scintigraphy to reduce the rate of misdiagnosed cases of IE when combined with standard diagnostic tests in several situations: when clinical suspicion is high but echocardiographic findings are inconclusive; when there is a need for differential diagnosis between septic and sterile vegetations detected at echocardiography; when echocardiographic, laboratory, and clinical data are contradictory; and when valve involvement (especially of a prosthetic valve) needs to be excluded during febrile episodes, sepsis, or postsurgical infections.

Carbapenem-Sparing Antibiotic Regimens for Infections Caused by Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae in Intensive Care Unit

A carbapenem-sparing regimen of tigecycline plus gentamicin or colistin was effective for treating 24 of 26 (92%) Klebsiella pneumoniae carbapenemase-producing K. pneumoniae infectious episodes in 22 polytrauma intensive care unit patients without comorbidities. The 30-day crude mortality rate was 14%. Regimens were considered appropriate in 12% of episodes according to the Vitek 2 System and in 100% based on E-test.

Synergistic activity of colistin plus rifampin against colistin-resistant KPC-producing Klebsiella pneumoniae.

ABSTRACT Infections caused by carbapenem-resistant KPC-producing Klebsiella pneumoniae are responsible for high rates of mortality and represent a major therapeutic challenge, especially when the isolates are also resistant to colistin. We used the checkerboard method to evaluate the synergistic activity of 10 antibiotic combinations against 13 colistin-resistant KPC-producing K. pneumoniae isolates (colistin MIC range of 8 to 128 mg/liter). Colistin plus rifampin was the only combination that demonstrated consistent synergistic bacteriostatic activity against 13/13 strains tested, reducing the colistin MIC below the susceptibility breakpoint (MIC ≤ 2 mg/liter) in 7/13 strains at rifampin concentrations ranging from 4 to 16 mg/liter. Bactericidal synergistic activity was also documented for 8/13 tested strains. Other antimicrobial combinations with carbapenems, gentamicin, and tigecycline showed variously synergistic results. Colistin plus rifampin also exhibited bacteriostatic synergistic activity against 4/4 colistin-susceptible KPC-producing K. pneumoniae isolates (colistin MIC range of 0.5 to 2 mg/liter) and 4/4 ertapenem-resistant extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolates (ertapenem MIC range of 16 to 32 mg/liter). Collectively, our data suggest that colistin plus rifampin is the most consistently synergistic combination against KPC-producing K. pneumoniae isolates, including colistin-resistant strains. Colistin-rifampin combinations may have a role in the treatment of multidrug-resistant K. pneumoniae and may possibly slow the selection of heteroresistant subpopulations during colistin therapy.

Microbiology of cardiac implantable electronic device infections

AIMS The aim of the study was to describe the microbiological findings of cardiac implantable electronic devices (CIEDs) infection in the 2000-2011 period at the Cardiology Unit of New Santa Chiara Hospital in Pisa (Italy). METHODS AND RESULTS Removed CIED leads and pocket material were seeded on solid media and isolates tested for antimicrobial susceptibility with the Kirby Bauer method. Electrodes from 1204 patients were analysed and 854 (70.9%) tested positive. In 663 (77.6%) cases only one species was isolated, in 175 (20.5%) two species, and in 14 (1.8%) >2 species. In 116 cases material from the pocket was also cultured. The result was consistent with that from the electrodes in 69 (59%) cases. In 359 cases a blood sample was also obtained for culture. The result was consistent with that from the leads in 124 (35%) cases. A total of 1068 strains were isolated from electrodes. Gram-positive organisms were most frequently isolated (92.5% of isolates); particularly, coagulase-negative staphylococci (CoNS), mainly Staphylococcus epidermidis, in 69% of cases and Staphylococcus aureus in 13.8%, Gram-negative rods in 6.1%, yeasts in 1% and molds in 0.4%. Overall, Oxacillin resistance was 30%, in particular 33% among CoNS and 13% among S. aureus. Oxacillin resistance and quinolones resistance have increased in the period 2006-2011 with respect to the 5 years before. Seventeen percent of Enterobacteriaceae strains had a phenotype compatible with extended spectrum beta-lactamase expression. CONCLUSIONS Culture of the leads offers the possibility of an aetiological diagnosis in the majority of cases. When material from the pocket can be obtained, the microbiological result is often consistent with that from the electrodes, while species isolated from blood cultures are often different and more likely to be the result of contamination. Cardiac implantable electronic device infection is more often monomicrobial, CoNS are most frequently isolated and S. epidermidis is largely the main single agent. Very early infections were associated with S. aureus infection. The pattern of susceptibility to antimicrobials is in general that of community-acquired infections, although oxacillin resistance and quinolones resistance has increased in the last 5 years.

Microbiological Activity and Clinical Efficacy of a Colistin and Rifampin Combination in Multidrug-Resistant Pseudomonas aeruginosa Infections

Abstract The aim of the study was to assess the microbiological activity and clinical efficacy of colistin and rifampin combination against multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The antimicrobial activity of the colistin/rifampin combination was evaluated using the checkerboard and time-kill curve methods against different MDR P. aeruginosa strains. The combination of rifampin and colistin resulted fully (1 strain) or partially (5 strains) synergistic for 6/7 strains and minimum inhibitory concentrations (MICs) in combination were reduced to easily obtainable therapeutic levels. The time-kill curves showed that the combination was bactericidal against the strains tested. The clinical efficacy of the combination was tested in four patients with difficultto treat infections (sepsis or pneumonia) caused by MDR P. aeruginosa. All infections were successfully treated. Our microbiological and clinical observations suggest that the addition of rifampin to colistin may result in a synergistic bactericidal combination that may be useful in patients with infections caused by MDR P. aeruginosa which are difficult to cure.

THE ROLE OF IMMUNOMODULATION IN ABO-INCOMPATIBLE ADULT LIVER TRANSPLANT RECIPIENTS

ABO‐incompatible (ABO‐i) liver transplantation (LT) is a high‐risk procedure due to the potential for antibody‐mediated rejection (AMR) and cell‐mediated rejection. The aim of the current report is to illustrate the results of a retrospective comparison study on the use of immunomodulation with therapeutic plasma exchange (TPE) associated to high‐dose immunoglobulins (IVIg) and extracorporeal photopheresis (ECP) in ABO‐i adult LT patients.

Clinical and microbiological efficacy of colistin therapy alone or in combination as treatment for multidrug resistant Pseudomonas aeruginosa diabetic foot infections with or without osteomyelitis.

Abstract We retrospectively evaluated the safety and effectiveness of colistin alone or in combination with other antimicrobials in eight diabetic patients with severe diabetic foot infections due to multidrug resistant (MDR) Pseudomonas aeruginosa, complicated in 4 cases by osteomyelitis. All patients received colistin after other ineffective antimicrobial treatment, when MDR P. aeruginosa strains were isolated by cultural examination and together with a multidisciplinary care approach including revascularization, surgical debridement and adequate offloading. The mean duration of therapy was 72 ± 52.9 days. Six out of 8 patients (75%) successfully benefited from colistin therapy, while 2 patients failed and/or experienced side effects that led to discontinuation of therapy. Serious adverse events (i.e. acute renal failure and pulmonary edema) were observed in 1 patient. Our data allow us to conclude that colistin, alone or in combination with other antimicrobials, is safe and effective when administered as part of a multidisciplinary approach, to promote healing of diabetic foot infection due to MDR P. aeruginosa.

Scintigraphic imaging of vertebral osteomyelitis with 111in-biotin.

Study Design. Early diagnosis of vertebral infection (hematogenous or postsurgical) is necessary to choose a correct therapy and to minimize dramatic complications. All patients suspected to have vertebral infection underwent radiologic imaging and 111In-Biotin scintigraphy. Objective. Biotin is a growth factor used by many bacteria. The aim of our study is to use 111In-Biotin to diagnose vertebral infections. Summary of Background Data. Magnetic resonance imaging, even if endowed with fairly good sensitivity and specificity, shows some limitations in the study of the onset of pathology and in postsurgical conditions. Conventional scintigraphic imaging, like bone scintigraphy with 99mTc-MDP, 67Ga-citrate scintigraphy, or Positron Emission Tomography with [18F]FDG, are limited by relatively low specificity; the use of Streptavidin/111In-Biotin scintigraphy, based on aspecific uptake of tracer in the site of infection, shows good results in term of sensibility and specificity but the use of heterologous protein might engender immunogenic reactions. Methods. All patients (pts) (n = 110) of the study underwent 111In-biotin scintigraphy 2 hours after intravenous injection of the tracer, 71 pts were suspected to have hematogenous vertebral infection (Group I) and 39 pts were suspected to have postsurgical infection (Group II). The reference for final diagnosis was either bacterial cultures, histopathologic analysis, and/or clinical/imaging follow-up for at least 1 year. Results. 111In-biotin scintigraphy showed a sensitivity of 84% and specificity of 98% in Group I and a sensitivity of 100% and specificity of 84% in Group II. Conclusion. Our results showed that 111In-Biotin scintigraphy possess high diagnostic accuracy. This technique is easy to perform and requires short imaging time-point after intravenous tracer injection. Moreover if 111In-Biotin uptake is due only to high proliferation rate of bacteria presents in site of infection, it will be further investigated to discriminate definitely bacterial from sterile inflammation.

Oral Gentamicin Gut Decontamination for Prevention of KPC-Producing Klebsiella pneumoniae Infections: Relevance of Concomitant Systemic Antibiotic Therapy

ABSTRACT Gut colonization represents the main source for KPC-producing Klebsiella pneumoniae (KPC-Kp) epidemic dissemination. Oral gentamicin, 80 mg four times daily, was administered to 50 consecutive patients with gut colonization by gentamicin-susceptible KPC-Kp in cases of planned surgery, major medical intervention, or need for patient transfer. The overall decontamination rate was 68% (34/50). The median duration of gentamicin treatment was 9 days (interquartile range, 7 to 15 days) in decontaminated patients compared to 24 days (interquartile range, 20 to 30 days) in those with persistent colonization (P < 0.001). In the six-month period of follow-up, KPC-Kp infections were documented in 5/34 (15%) successfully decontaminated patients compared to 12/16 (73%) persistent carriers (P < 0.001). The decontamination rate was 96% (22/23) in patients receiving oral gentamicin only, compared to 44% (12/27) of those treated with oral gentamicin and concomitant systemic antibiotic therapy (CSAT) (P < 0.001). The multivariate analysis confirmed CSAT and KPC-Kp infection as the variables associated with gut decontamination. In the follow-up period, KPC-Kp infections were documented in 2/23 (9%) of patients treated with oral gentamicin only and in 15/27 (56%) of those also receiving CSAT (P = 0.003). No difference in overall death rate between different groups was documented. Gentamicin-resistant KPC-Kp strains were isolated from stools of 4/16 persistent carriers. Peak gentamicin blood levels were below 1 mg/liter in 12/14 tested patients. Oral gentamicin was shown to be potentially useful for gut decontamination and prevention of infection due to KPC-Kp, especially in patients not receiving CSAT. The risk of emergence of gentamicin-resistant KPC-Kp should be considered.