Cinzia Cala

Outbreak of Infection with Klebsiella pneumoniae Sequence Type 258 Producing Klebsiella pneumoniae Carbapenemase 3 in an Intensive Care Unit in Italy

Gram-negative pathogens producing carbapenemases represent an alarming clinical threat with serious effects on patient outcomes ([3][1], [7][2]). In 2001, Yigit et al. ([11][3]) reported a novel β-lactamase termed “ K lebsiella pneumoniae carbapenemase” (KPC-1) in North Carolina. KPC-producing

Prevalence of virulence-associated genotypes of Helicobacter pylori and correlation with severity of gastric pathology in patients from western Sicily, Italy

In a bacterium like Helicobacter pylori, which is characterized by a recombinant population structure, the associated presence of genes encoding virulence factors might be considered an expression of a selective advantage conferred to strains with certain genotypes and, therefore, a potentially useful tool for predicting the clinical outcome of infections. However, differences in the geographical and ethnic prevalence of the H. pylori virulence-associated genotypes can affect their clinical predictive value and need to be considered in advance. In this study we carried out such an evaluation in a group of patients living in Sicily, the largest and most populous island in the Mediterranean Sea. cagA, vacA, babA2, hopQ, oipA, sabA, and hopZ were the H. pylori virulence-associated genes assayed; their presence, expression status or allelic homologs were detected in H. pylori DNA samples and/or isolated strains, obtained by gastric biopsy from 90 Sicilian patients with chronic gastritis, inactive (n = 37), active (n = 26), or active with peptic ulcer (n = 27). Genotypes cagA+, vacAs1, vacAm1, babA2+, and hopQ I, I/II were identified in 51.8, 80.4, 35.2, 47.3, and 67.7% of the different samples respectively. Only these genotypes were associated with each other and with the active form of chronic gastritis, irrespective of the presence of a peptic ulcer. In our isolates their prevalence was more similar to values observed in the north of Italy and France than to those observed in Spain or other Mediterranean countries that are closer and climatically more similar to western Sicily.

Ventilator-associated Pneumonia and MRSA ST398, Italy

To the Editor: Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST)398 has become increasingly common in livestock, particularly pigs, in some countries in Europe, such as Spain and Germany (1). In Italy, prevalences as high as 14% and 21.6% in pig-breeding facilities and meat-processing sites, respectively, have been recently reported (1). Possible association of MRSA in animals with infection in humans has been investigated. One study showed a strong relationship between contact with pigs or calves and carriage by persons having direct contact with animals and families of persons who handle animals (2). Moreover, an MRSA prevalence >11.9% has been described by de Boer et al. (3) in meat, with 85% of isolates belonging to the ST398 lineage. MRSA ST398 has been described as a lineage with limited virulence and ability to spread between humans, but severe clinical manifestations, such as wound infections and endocarditis, have been recently attributed to this clone (1,4). Cases of nosocomial ventilator-associated pneumonia have also been reported in Germany (1). Moreover, an outbreak of infection with MRSA ST398 occurred in a surgical ward of a hospital in the Netherlands in 2007 (5). MRSA ST398 is an infrequent cause of human infections in Italy. No isolates belonged to this lineage in 2 studies of MRSA in Italy during 2006–2007 (6) or in hospitals during 1990–2007 (7). Only 1 invasive infection has been recently reported in a pig farm worker (8). We report a case of ventilator-associated pneumonia caused by MRSA ST398 in a patient in Palermo, Italy. The patient and his household members did not report any exposure to companion or livestock animals. The case-patient was a 78-year-old man admitted to a cardiac intensive care unit (ICU) of ARNAS Ospedale Civico Di Cristina e Benfratelli in Palermo on January 31, 2009, because of a recent history of unstable angina pectoris and acute anemia caused by duodenal ulcers. After cardiocirculatory arrest, he was transferred to a general ICU on February 3. The patient had type 2 diabetes and ischemic-hypertensive cardiomyopathy. MRSA nasal colonization at admission was not investigated because the patient lacked risk factors for screening at admission, e.g., antimicrobial drug therapy, hospitalization for >48 hours or time in a long-term care facility within the past 6 months, need for long-term nursing care, presence of indwelling devices, or chronic skin lesions. The clinical course of the patient’s illness was characterized by serious hemodynamic instability and difficulty in weaning from mechanical ventilation. Two bronchial aspirate specimens were cultured on February 4 and 9, when he was being treated with a third-generation cephalosporin (ceftriaxone). These cultures showed Staphylococcus epidermidis and S. saprophyticus. On the 14th day in the ICU, clinical signs of ventilator-associated pneumonia developed in the patient. He had increased sputum production, fever (38.8°C), leukocytosis, and infiltrates were seen on a chest radiograph. Empiric antimicrobial drug therapy with glycopeptides and a β-lactam/β-lactamase inhibitor combination was started. Culture of bronchial secretions yielded MRSA that was susceptible to glycopeptides, rifampin, linezolid, macrolides, and sulfamethoxazole and resistant to fluoroquinolones and tetracyclines. Three days later, linezolid was given, but the patient died after an acute myocardial infarction. The isolate was identified genetically by mecA PCR. It was not typeable by pulsed-field gel electrophoresis after digestion with SmaI, negative for Panton-Valentine leukocidin, and carried staphylococcal cassette chromosome mec (SCCmec) type IVa (9). Multilocus sequence typing, performed according to a recommended procedure (http://saureus.mlst.net/misc/info.asp), identified the isolate as ST398. A 1-year epidemiologic survey on MRSA isolates from 4 general hospitals in Palermo, which had begun on February 2009, did not identify any MRSA isolate carrying SCCmec type IV or V in patients admitted to the ICU until September 2009. However, colonization or infection by MRSA ST398 in the ICU patients before the study period could not be ruled out. Although an MRSA screening policy for the ICU staff members was not being carried out, a nosocomial chain of transmission appeared to be unlikely. Our results indicate that a new zoonotic clone of MRSA is emerging as a potential cause of serious human infections. Screening at hospital admission would likely help efforts to determine whether exposure to pet animals and livestock had occurred. However, the absence of specific exposure to zoonotic clonal lineages, as in our case-patient, is a matter of concern in terms of screening and contact tracing policy for MRSA infections. Prevalence of MRSA and distribution of MRSA sequence types in livestock in Italy are not known. However, surveys of foods of animal (pig) origin have showed an MRSA prevalence of 3.7% (1,10). In view of the low prevalence of MRSA ST398 in patients with no exposure to animals, food products currently seem to play a negligible role. However, this clone is likely spreading because of the large animal reservoir of ST398 and the global market for meat and livestock. The changing epidemiology of MRSA indicates that collaborative surveillance plans integrating human and animal information should be increased.

Epidemiology and clonality of carbapenem-resistant Acinetobacter baumannii from an intensive care unit in Palermo, Italy

BackgroundMultidrug-resistant Acinetobacter baumannii, initially considered as having a poor clinical relevance, is frequently isolated from infection cases in intensive care units. We describe the epidemiology of carbapenem resistant A. baumannii (CRAB) in a general ICU in Palermo, Italy, from October 2010 to March 2011.Findings58 of 61 isolates exhibited MICs for meropenem or imipenem ≥16 mg/L. Forty-nine carried blaOXA-23 and two blaOXA-58 genes.Five subtype clusters were detected by rep-PCR. Clusters D and E included 10 isolates that tested negative for the carbapenem resistance genes. MLST attributed all isolates, but two, with sequence type (ST)2, whereas the two remaining isolates with ST78.The respiratory tract was the most common site of infection (26 out of 36 cases. 72.2%). A high infection related mortality rate was observed (18 out of 35 patients, 51.4%). Nineteen patients tested positive for other multidrug resistant organisms in addition to CRAB. In eight cases isolates belonging to distinct subtype clusters and/or with distinct carbapenemase profiles were identified.ConclusionsCarbapenem resistance was prominently driven by the dissemination of CRAB isolates belonging to ST2, carrying the carbapenemase gene blaOXA-23. The colonization/infection of some patients by multiple strains is suggestive of an endemic circulation of CRAB.

Characterization of Acinetobacter baumannii from intensive care units and home care patients in Palermo, Italy

In this study 45 isolates of Acinetobacter baumannii identified from patients in intensive care units of three different hospitals and from pressure ulcers in home care patients in Palermo, Italy, during a 3-month period in 2010, were characterized. All isolates were resistant to at least three classes of antibiotics, but susceptible to colistin and tygecycline. Forty isolates were non-susceptible to carbapenems. Eighteen and two isolates, respectively, carried the bla(OXA-23-like) and the bla(OXA-58-like) genes. One strain carried the VIM-4 gene. Six major rep-PCR subtype clusters were defined, including isolates from different hospitals or home care patients. The sequence type/pulsed field gel electrophoresis group ST2/A included 33 isolates, and ST78/B the remaining 12. ST2 clone proved to be predominant, but a frequent involvement of the ST78 clone was evident.

Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline Evaluation and Surveillance Trial.

Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae, during this time. Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A. baumannii increased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide. ABSTRACT Multidrug-resistant (MDR) Gram-negative organisms are a burden on the global health care system. The Tigecycline Evaluation and Surveillance Trial (TEST) is an ongoing global study designed to monitor the in vitro activities of tigecycline and a panel of marketed antimicrobials against a range of clinically significant pathogens. In this study, in vitro data are presented for MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, and Enterobacter cloacae isolates collected from 2004 to 2014. In total, 13% (21,967/170,759) of isolates displayed multidrug resistance globally, with the highest rates recorded among A. baumannii (overall rate, 44% [8,294/18,741], increasing from 23% [309/1,323] in 2004 to 63% [447/712] in 2014). Other multidrug resistance rates ranged from 2.5% for K. oxytoca (203/8,000) to 12% for P. aeruginosa and K. pneumoniae (3,951/32,786 and 3,895/32,888, respectively), and rates among these pathogens remained stable during the study period. Against MDR E. coli, Klebsiella spp., and E. aerogenes, the lowest rates of resistance were to tigecycline (0.2%, 6%, and 12%, respectively), and the lowest MIC90 value against A. baumannii was observed for tigecycline (2 mg/liter; MIC range, ≤0.008 to ≥32 mg/liter). The only significant change in resistance to tigecycline during the study period was for MDR E. coli (P < 0.01), among which eight resistant isolates were identified globally from 2009 to 2013. In summary, these results show that tigecycline retained in vitro activity against the majority of MDR Gram-negative organisms presented here, but the rising rates of MDR A. baumannii highlight the need for the continued monitoring of global multidrug resistance. IMPORTANCE Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae, during this time. Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A. baumannii increased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide.

Polyclonal non multiresistant methicillin resistant Staphylococcus aureus isolates from clinical cases of infection occurring in Palermo, Italy, during a one-year surveillance period

BackgroundThe evolving epidemiology of methicillin resistant Staphylococcus aureus (MRSA) is characterized by the emergence of infections caused by non multiresistant MRSA carrying staphylococcal chromosomal cassette (SCC)mec IV or V in the healthcare settings. A molecular epidemiological analysis of non multiresistant MRSA isolates from four acute general hospitals was performed in Palermo, Italy, during a one year period.MethodsFor the purpose of the study, MRSA isolates were defined as non multiresistant when they were susceptible to at least three classes of non β-lactam antibiotics. Seventy-five isolates were submitted to antimicrobial susceptibility testing, multilocus sequence typing (MLST) and polymerase chain reaction (PCR) for SCCmec, accessory gene regulator (agr) groups, arginine catabolic mobile element (ACME) and Panton Valentine leukocidin (PVL) toxin genes. For epidemiological typing, Multiple-Locus Variable-Number Tandem Repeat Fingerprinting ( MLVF) was performed on all isolates and pulsed field gel electrophoresis (PFGE) on ST8 isolates.ResultsNon multiresistant MRSA isolates were isolated from all hospitals. Resistances to ciprofloxacin, macrolides and tetracycline were the most prevalent. MLST attributed 46 isolates with ST22, 13 with ST8, eight with ST1, three with ST50 and three with ST398. SCCmec type IV was found in all isolates. PVL was detected in one ST22 isolate. All isolates tested negative for the ACME element. MLVF identified 31 different patterns, some subtype clusters ranging in size between two and 22 isolates. The closely related PFGE patterns of the ST8 isolates differed from USA300.ConclusionsA polyclonal circulation of non multiresistant MRSA along with blurring of boundaries between healthcare associated (HA)-MRSA and community associated (CA)-MRSA appear to be occurring in our epidemiological setting. A better understanding of spread of MRSA with the support of molecular typing can provide invaluable information in the epidemiological, microbiological and clinical fields.

Role of environmental and genetic factor interaction in age-related disease development: the gastric cancer paradigm.

The association of Helicobacter pylori (Hp) infection with gastric cancer is well known and might be considered a paradigmatic example of the role that interaction among environmental factors and individual background might play in inducing age-associated disease. To evaluate the role of interaction of Hp infection with genetic background, gastric cancer and chronic gastritis patients as well as random selected controls were typed for five inflammation-related polymorphisms of IL-1 and IL-10 cytokine genes. No association among IL-10 or IL-1 variants with an increased risk of gastric cancer was found, whereas an Hp-independent association of IL-1beta -511T positive genotypes to an increased risk of chronic gastritis was found (Hp-/511T+ OR 1.89, 95% CI: 1.01-3.54; Hp+/-511T+ OR 1.83, 95% CI: 1.05-3.19). Stratification of gastric cancer group according to Hp infection does not allow finding a statistically significant association of Hp+ to the higher histological grading (G3) of gastric cancer (OR 1.54, 95% CI: 0.46-5.11). Our findings seem to confirm that cytokine genetic variants might contribute to determining the background for inflammaging in which H. pylori infection might facilitate cancer development.

Daptomycin non-susceptible, vancomycin intermediate methicillin-resistant Staphylococcus aureus ST398 from a chronic leg ulcer, Italy

Human infections caused by methicillin-resistant Staphylococcus aureus (MRSA) sequence type 398 (ST398) have been emerging in recent y in Europe [1 – 3]. Most studies have shown a strong, but not exclusive, relationship with pig farming. In Italy, prevalences as high as 14% and 21.6% in pig breeding and production holdings, respectively, have been reported [3,4]. As a consequence of spread in productive livestock, MRSA can also contaminate meat products [4]. MRSA ST398 has been described as a lineage with limited ability to spread between humans, but severe clinical manifestations have recently been attributed to this clone. In Italy, some clinically relevant infections, ranging from skin and soft tissue infections [5,6] to ventilatorassociated pneumonia [7], have been described in the last y. Daptomycin is a cyclic lipopeptide antibiotic active against Gram-positive organisms, including MRSA. However, recent reports have described the development of in vitro daptomycin non-susceptibility in association with daptomycin clinical treatment failures in MRSA infections [8,9]. We report a case of human infection caused by a MRSA ST398 that after treatment acquired a vancomycin-intermediate and daptomycin non-susceptible phenotype. The case-patient was a 30-y-old housewife who had been submitted since the age of 14 y to multiple surgical interventions because of a congenital arteriovenous malformation in her left foot. The patient had also been treated with multiple courses of antibiotic therapy (aminoglycosides, third-generation cephalosporins and co-trimoxazole) on an empirical basis. At the time of her fi rst admission to the Vascular Surgery Unit of the ARNAS General Hospital “ Civico, Di Cristina e Benfratelli ” on 21 January 2010, she was being conservatively treated with topical gentamicin. She and her family were living in a semi-rural area in the province of Palermo, Italy, but did not report direct contact with livestock or pet animals. Culture from skin lesions yielded MRSA and Pseudomonas aeruginosa. The MRSA strain was Panton – Valentine leukocidin (PVL)-negative and carried SCC mec IVa. Multilocus sequence typing (MLST) was performed following the recommended procedure (http://saureus.mlst.net/misc/info.asp) and attributed the isolate to ST398. Antimicrobial susceptibility testing was carried out using the VITEK-2 system (bioM é rieux, Marcy l ’ Etoile, France). The MRSA was susceptible to rifampin, fl uoroquinolones, co-trimoxazole, linezolid, tigecycline and glycopeptides, with a minimum inhibitory concentration (MIC) for vancomycin of 2 μ g/ml and teicoplanin of 0.5 μ g/ml, and resistant to aminoglycosides, macrolides and tetracycline. The MIC for daptomycin by E-test (AB-Biodisk) was 0.094 μ g/ml. Therapy with co-trimoxazole was started. To establish the MRSA nasal colonization status of the patient and trace the possible source of this strain, on 19 March nasal swabs were taken from the patient and her 6 cohabiting relatives. Skin lesions of LETTER TO THE EDITOR

Colonization of pressure ulcers by multidrug-resistant microorganisms in patients receiving home care.

Abstract Colonization and/or infection with multidrug-resistant microorganisms (MDRO) of pressure ulcers in patients receiving care at home have seldom been investigated. The objective of this study was to assess the prevalence of MDRO colonization in pressure ulcers of patients receiving home care in Palermo, Italy. Vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and multidrug-resistant Gram-negative bacilli (MDRGN) were isolated, identified, and characterized from pressure ulcers and selected home environment surfaces. Thirty-two patients were enrolled, of whom 12 were under antimicrobial therapy. Five patients had been admitted to hospital in the preceding year. Nineteen patients tested positive for 1 or more MDROs. In particular, 1 patient was colonized by a vanA-containing strain of VRE, 5 by MRSA, and 17 by MDRGN of different species. Our findings suggest that pressure ulcers in home care patients could play a role in bringing MDROs into the community setting.