Methicillin-resistant Staphylococcus aureus: epidemiology and antimicrobial susceptibility experiences from the University Hospital 'Luigi Vanvitelli' of Naples.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the important pathogens worldwide showing resistance to several widely used antibiotics. This has made the treatment of MRSA infections harder, especially due to their prevalence in the hospital setting. We evaluated the antibiotic susceptibility patterns of healthcare-associated MRSA infections with a focus on Vancomycin Intermediate S. Aureus (VISA) and macrolide-licosamide-streptogramin B (MLSB) phenotypes. A total of 417 Staphylococcus aureus (S. aureus) cases were isolated between January 2017 and December 2018, through several clinical specimens collected from the University Hospital 'Luigi Vanvitelli' of Naples. We identified bacterial strains using Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) and antimicrobial susceptibility using Phoenix BD (Becton Dickinson, NJ, USA). Out of the total 417 S. aureus cases, 140 were MRSA (33.6%) and of these, 50% were soft tissue infections. All MRSA and Methicillin sensible S.aureus MSSA isolates were susceptible to linezolid and daptomycin. Two MRSA cases exhibited intermediate resistance to vancomycin and were of constitutive MLSB phenotype. Among the MRSA strains, 11.4% were constitutive and 43.6% were inducible MLSB phenotypes and 8.6% were macrolide-streptogramin B phenotype. This study characterized the epidemiological status, antibiotic resistance patterns, and current prevalent phenotypes of healthcare-associated MRSA. This knowledge can aid clinicians in improving the antimicrobial stewardship program by adapting appropriate guidelines for the proper use of MRSA antibacterial agents.

The effect of an antimicrobial stewardship programme in two intensive care units of a teaching hospital: an interrupted time series analysis.

OBJECTIVES: To evaluate the effect of an antimicrobial stewardship programme in two intensive care units (ICUs) of a teaching hospital. METHODS: Between January 2017 and June 2018 we conducted a prospective, interventional, interrupted time-series study, based on Prospective Audit and Feedback in two ICUs of an acute-care teaching hospital. The primary outcomes were the difference in the antibiotic consumption, and the incidence of bloodstream infections (BSI) caused by multidrug-resistant (MDR) organisms. The secondary outcomes included the hospital mortality rate, the mean length of stay and the antibiotic expense. RESULTS: During the study, 231 audits were performed, evaluating 693 antibiotic prescriptions. The programme led to a global reduction in antibiotic consumption, with a change in level (CL) of -324.8 defined daily doses (DDD)/100 patient-days (PD), p 0.04, and particularly in the use of fluoroquinolone: (CL: -63.48 DDD/100 PD, p < 0.001). A non-significant reduction was obtained for the consumption of carbapenems (CL: -34.7 DDD/100 PD, p 0.25) and third- and fourth-generation cephalosporins (CL: -27.3 DDD/100 PD, p 0.102). Furthermore, we registered a significant decrease in all BSI (CL: -5.8 events/100 PD, p 0.026) and in BSI due to MDR Gram-negative organisms (CL: -2.96 events/100 PD, p 0.043). No difference was observed in the hospital mortality and length of stay. CONCLUSIONS: Our study demonstrated that implementation of an antimicrobial stewardship programme in two ICUs of a teaching hospital induced a significant reduction in antibiotic consumption and in the incidence of BSI due to MDR Gram-negative organisms, without any impact on the mortality rate.

Induction of VEGF and MMP-9 expression by toll-like receptor 2/4 in human endothelial cells infected with Chlamydia pneumoniae.

Matrix metalloproteinases (MMP) are a family of host-derived enzymes involved in the turnover of extracellular matrix (ECM) molecules, and, in particular, it is demonstrated that the 92 KDa gelatinase MMP-9 is often expressed in atherosclerotic plaques by macrophages and smooth muscle cells. Recent evidence supports a role of Toll-like receptor (TLR) signaling in the development of atherosclerosis lesions. In this study, we analyzed the TLR2/TLR4 expression in HUVEC infected with C. pneumoniae and correlated it to the production of VEGF and MMP-9. The results obtained showed an increased VEGF and MMP-9 production correlated with a time-dependent increase in cellular proliferation in HUVEC infected with C. pneumoniae at a multiplicity of infection (MOI) of 2 IFU/cell. HUVEC preincubated with VEGF antibody did not release MMP-9, as detected by zymography assessment and ELISA assay. In addition, we demonstrated that TLR2/TLR4 are expressed in HUVEC infected with viable microorganisms (25% and 17%, respectively), while UV-inactivated microorganisms induced a lesser expression (20% and 11%, respectively) compared to control cells and HUVEC exposed to heat-killed bacteria showed a percentage of TLR-expressing cells similar to the control cells. In addition, the cells preincubated for 60 min with TLR2/TLR4 neutralizing antibodies showed a decrease in C. pneumonia-induced VEGF and MMP-9 production.

Failure of first-line eradication treatment significantly increases prevalence of antimicrobial-resistant Helicobacter pylori clinical isolates.

OBJECTIVES: Helicobacter pylori infection is a major health problem worldwide, and effective eradication of the infection is mandatory. The efficacy of recommended eradication regimens is approximately 70%. To avoid treatment failure and the consequent development of secondary resistance(s), it is important to choose the most appropriate first-line treatment regimen. This choice should also be made based on the knowledge of the antimicrobial resistance peculiar to a given geographical area. We evaluated the prevalence of antimicrobial-resistant H pylori strains isolated from naive patients and from patients with previous unsuccessful treatments. METHODS: This study examined 109 H pylori-infected subjects (Group 1) who had never received an eradication treatment and 104 H pylori-infected subjects (Group 2) who had failed one or more eradication treatments. Resistance to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MET) and levofloxacin (LEV) was determined using the epsilometer test. The significance of differences was evaluated by the chi2 test. RESULTS: The prevalence of antimicrobial resistance was 0% versus 3.1% to AMO, 0% versus 2% to TET, 27% versus 41.3% to MET (p<0.05), 18% versus 45.8% to CLA (p<0.05) and 3% versus 14.6% to LEV (p<0.05) in Group 1 vs Group 2, respectively. In Group 2, there was an increased prevalence of H pylori strains resistant to multiple antimicrobials. CONCLUSIONS: This study confirms the high prevalence of H pylori strains resistant to CLA and MET, and indicates that unsuccessful treatments significantly increase resistance. Choosing eradication regimens other than standard triple therapy as a first-line therapy should be advisable in areas with high primary antimicrobial resistance prevalence.

Central serous chorioretinopathy and Helicobacter pylori.

PURPOSE: This study was designed to evaluate the prevalence of Helicobacter pylori infection in patients with central serous chorioretinopathy (CSC). METHODS: Retrospective observational case series. A group of 23 patients (22 men and 1 woman, age range 34-62 years, median age 47 years) with diagnosis of CSC, confirmed by fluorescein angiogram, and a control group of 23 consecutive patients (22 men and 1 woman, age range 41-69 years, median age 50 years) referred to our Department for retinal disease other than CSC were studied. Each patient provided peripheral venous blood samples and a stool specimen, which were analyzed at the Department of Gastroenterology and Microbiology at the same university. H. pylori infection was determined by measurement of IgG anti-bodies to H. pylori and by determination of H. pylori antigens in the stool specimens by enzyme-linked immunosorbent assay technique. Patients were defined as H. pylori infected if both tests were positive. RESULTS: The prevalence of H. pylori infection was 78.2% (95% CI, 56%-92%) in CSC patients and 43.5% (95% CI, 23%-65%) in control subjects (p<0.03 by two-tail ed Fisher exact test). The odds ratio for CSC associated with H. pylori infection was 4.6 (95% CI 1.28-16.9). CONCLUSIONS: The results of this study show that the prevalence of H. pylori infection seems to be significantly higher in patients with CSC than in control s. H. pylori infection may represent a risk factor in patients with CSC.

Selection for aneuploid potato hybrids combining a low wild genome content and resistance traits from Solanum commersonii.

A breeding scheme based on the production of progenies with odd ploidy was followed to introduce useful genes from the wild Solanum commersonii (cmm) into S. tuberosum (tbr) genome. Hybrids from 5 x x 4 x crosses were characterized for traits of interest, and selection was assisted by amplified fragment length polymorphism (AFLP) analysis. As expected, most of the hybrids were aneuploids, with a trend towards a low degree of aneuploidy. Despite the fact that aneuploidy has often been associated with a reduction in male and female fertility, most of the hybrids were fertile following crosses with tbr, making it possible to produce viable offspring. A screening for resistance traits deriving from cmm was also carried out. With respect to freezing resistance, the killing temperatures of cold-acclimated genotypes were distributed between the wild and cultivated parental values, with some hybrids displaying an acclimation capacity higher than 3 degrees C. A wide variability was also found for tuber soft rot resistance, and hybrids with high levels of resistance were identified. Selection of hybrids was based on a two-stage scheme that consisted of conventional phenotypic selection followed by an estimation of the wild genome content still present in order to identify hybrids combining noteworthy traits with a low wild genome content. Previously selected cmm-specific AFLPs were used to monitor the degree of wild genome content still present in each hybrid. The percentage of cmm-specific markers ranged from 59% to 91%, with an average value of 75%. AFLP analysis was employed to assist in the selection of valuable hybrids for further breeding efforts.

Antimicrobial action of Nitens mouthwash (cetyltrimethylammonium naproxenate) on multiple isolates of pharyngeal microbes: a controlled study against chlorhexidine, benzydamine, hexetidine, amoxicillin, amoxicillin-clavulanate, clarithromycin, and cefaclor.

BACKGROUND: Acute oropharyngeal and respiratory tract infections are due to a wide spectrum of microorganisms. The aim of this study was to compare and evaluate the in vitro activity of four antiseptics (cetyltrimethylammonium naproxenate, chlorhexidine, benzydamine, hexetidine) to four antibiotics (amoxicillin, amoxicillin-clavulanate, clarithromycin, cefaclor) on strains of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae. METHODS: Susceptibility tests were performed on 90, aerobic and anaerobic, bacterial strains, isolated from nasopharyngeal swabs and sputum. Minimum inhibitory concentrations (by microdilution) and minimum bactericidal concentrations were determined and compared. RESULTS: Our selected panel of bacteria was highly susceptible to the antiseptics, particularly to chlorhexidine and naproxenate, even more so than two of the most frequently used antibiotics. Data were statistically significant (p < 0.005). CONCLUSIONS: In view of their bactericidal and anti-inflammatory properties, these antiseptics may be effective in controlling the transitory colonization of the oral cavity by microbes that cause or worsen disease in patients with mild infections.

Peptic ulcer occurrence in follow-up of chronic gastritis in patients with treated and not eradicated CagA-positive Helicobacter pylori infection.

The aim of the present prospective investigation was to study 49 dyspeptic Helicobacter pylori (HP)-positive (HP+) or -negative (HP), CagA+ and CagA- patients with a normal pattern or pure chronic gastritis at initial histology as well as normal features or hyperemic gastropathy at initial endoscopy in a two-year follow up. All the HP+ patients were treated with omeprazole 20 mg twice a day plus amoxicillin 1 g twice a day for two weeks. No substantial change was seen in gastritis in CagA+ patients in whom the infection was not eradicated, and, in contrast, a progressive improvement in 13/14 successfully treated patients was found. At endoscopy, a progressive change to a normal picture was seen in 8 and no change in 6 of 14 patients whose HP infection was eradicated, in contrast a worsening in the 9 HP+ patients who were still infected was observed. In particular, peptic lesions arose in 6 of 21 CagA+ patients in whom the infection was not eradicated. In conclusions, the lack of change in chronic gastritis at histology and the progressive worsening of endoscopic hyperemic gastropathy (with peptic lesions arising in 28,6%) when HP+ CagA+ infection is not eradicated, unlike the progressive improvement of the anatomoclinical condition in the patients whose infection was eradicated, draws attention to the relevance of eradicating HP in CagA+ patients even when no peptic lesion is found at initial endoscopy.

Prevalence of antimicrobial resistance in eighty clinical isolates of Helicobacter pylori.

We studied the in vitro susceptibility of 80 Helicobacter pylori clinical isolates to several antimicrobials commonly used to treat the infection, using the Epsilometer test (E-test). We also compared E-test and disk diffusion test in determining H. pylori susceptibility to the same antibiotics. We found a high prevalence of H. pylori strains resistant to metronidazole (23.7%), whereas the prevalence of H. pylori strains resistant to clarithromycin was 10%. Also, a significant correlation was found between MICs obtained with the disk diffusion test and E-test for metronidazole and clarithromycin. In conclusion, our study confirms a high prevalence of metronidazole- or clarithromycin-resistant H. pylori strains. Also, our data suggest that the E-test is a single, reliable, and cost-effective method to assess in vitro susceptibility of H. pylori to antimicrobial agents commonly used to eradicate the infection.

The in vitro effects of cetyltrimethylammonium naproxenate on oral and pharyngeal microorganisms of various ecological niches.

The purpose of this study was to determine the in vitro susceptibility to cetyltrimethylammonium naproxenate for various aerobic and anaerobic micro-organisms responsible for oral and pharyngeal diseases by assessing the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) or minimum fungicidal concentrations (MFCs) and by determining kill-times. The MICs of cetyltrimethylammonium naproxenate for 46 tested strains (25 reference strains and 21 clinical isolates) ranged from 8 to 500 micrograms/ml. The MIC was found to be 31.25 micrograms/ml for 36% of the reference strains. Even lower MIC values (15.63 micrograms/ml) were observed for some anaerobic strains, for Haemophilus influenzae and for Candida tropicalis. MIC and MBC values corresponded for the majority of strains tested while the MFC for C. tropicalis and C. albicans was much higher. Only 9.5% of the clinical isolates gave a MIC value of 31.25 micrograms/ml. Enterococcus faecalis, Streptococcus pyogenes and Staphylococcus aureus showed MIC at 62.5 micrograms/ml. The MIC and MBC values among the isolates were comparable, while the MFC value for the yeasts was greater. A concentration of 125 micrograms/ml of cetyltrimethylammonium naproxenate inhibited the growth of all bacteria, except Enterobacteriaceae and Pseudomonaceae, and yeasts. Cetyltrimethylammonium naproxenate shows very rapid kill-time for S. sanguis (0"), and rapid (15") for S. pyogenes, S. dysgalactiae and S. mutans and for Moraxella catarrhalis, while a longer kill-time was necessary for the other microbes tested.

Pefloxacin versus chloramphenicol in the therapy of typhoid fever.

An open, randomized clinical study was carried out to compare the clinical efficacy and safety of pefloxacin with that of chloramphenicol in the treatment of typhoid fever. Sixty hospitalized patients (40 men and 20 women, aged from 17 to 64 years), affected by severe proven typhoid sepsis, were randomly assigned to treatment with pefloxacin at a daily dose of 1,200 mg for 15 days (Group A) or with chloramphenicol at a daily dose of 2 g for 15 days (Group B). The two groups of patients were statistically homogeneous regarding both age and sex and all patients were followed for 30 days after the end of therapy. In Group A all the patients completely recovered from infection and all the isolated strains of Salmonella typhi were eradicated by pefloxacin treatment. In Group B two patients had a relapse, two patients became chronic enteric carriers of S. typhi and only 26 patients recovered from infection with complete eradication of the pathogen. The results indicate that pefloxacin is as active as chloramphenicol in the therapy of typhoid fever and that pefloxacin could be a valid antibacterial agent to be used together with appropriate hygienic measures for an eradication program of typhoid fever in the endemic countries.

Clinical evaluation of the imipenem/cilastatin combination in the therapy of severe infections in patients with malignant diseases.

Thirty hospitalized patients (23 men and 7 women), aged 42 to 78 years, with impaired host defences for malignant underlying diseases and affected by life-threatening infections, were treated with the imipenem/cilastatin combination at a dosage ranging between 2 and 4 g daily i.v. at 8 or 12 h intervals. The average length of therapy was 9.6 +/- 2.09 days. The isolated organisms were as follows: Pseudomonas aeruginosa [12], Escherichia coli [10], Klebsiella pneumoniae [5], Proteus mirabilis [3], P. vulgaris [2], Serratia marcescens [1], Staphylococcus aureus [3], Streptococcus faecalis [3], Bacteroides fragilis [5]. In fourteen patients a mixed infection was observed. Twenty-three patients (76.66%) were completely cured of infection and 35 out of 44 isolated organisms (79.54%) were eradicated. No important side-effects were observed.

Cefoperazone therapy of bacterial meningitis: a clinical trial.

Sixteen hospitalized patients, aged between 10 and 76 years (mean: 34.3 years), with bacterial meningitis were treated i.v. with cefoperazone at daily doses of 4.5 g to 9 g. In two cases ampicillin was given in combination with cefoperazone during the last four days and the first five days of treatment, respectively. The following organisms were isolated: Neisseria meningitidis (n = 9), Haemophilus influenzae (n = 3), Escherichia coli (n = 2), Streptococcus pneumoniae (n = 2). Fourteen patients completely recovered from infection and the pathogens were eradicated; the treatment failed in only two patients and both were cured with alternative treatment. Furthermore, in 11 patients cefoperazone serum and CSF levels were determined four times during the first week of treatment (1st, 3rd, 5th and 7th days). No important side effects were recorded.

Clinical experience with ofloxacin (DL-8280) in the therapy of various infections.

Thirty-four hospitalized patients with various infections: 19 with typhoid fever, 4 with gastroenteritis, 7 with lower respiratory tract infections, 2 with biliary tract infections, 1 with brucellosis and 1 with infection of necrotic ulceration of the feet, were treated with ofloxacin at a daily dosage ranging between 600 and 900 mg orally. Thirty-one of 34 patients (91.18%) completely recovered and pathogens were eradicated. In 2 patients, both with respiratory tract infections, the treatment failed and in one patient, affected by infection of necrotic ulcerations of the feet, improvement was registered. No side effects were recorded. Ofloxacin can be considered a safe and effective antimicrobial agent in the therapy of these infections.

[Comparative evaluation of norfloxacin and cinoxacin in the therapy of complicated infections of the urinary tract]. / Valutazione comparativa della norfloxacina e della cinoxacina nella terapia delle infezioni complicate delle vie urinarie.

A randomized clinical study was conducted in order to compare the effectiveness of norfloxacin and cinoxacin in complicated urinary tract infections. Norfloxacin proved effective in 80% of the 40 patients treated, cinoxacin in only 60%.

Clinical experience with pefloxacin in the therapy of typhoid fever.

Thirty hospitalized patients (22 men and eight women), aged between 15 and 41 years (mean = 25.4 years), with severe proven typhoid sepsis were treated with pefloxacin at daily dose of 1200 mg, divided in three doses, intravenously for the first five days and orally for the following ten days of treatment. All patients completely recovered from infection and pathogens were eradicated after 30 days of follow-up. In none of the patients was a relapse registered during the follow-up or enteric carrier state after disease. Pefloxacin therapy was well tolerated by all patients: in five patients a mild and transient epigastric pain and in one patient a mild and transient nausea were registered. Pefloxacin is a safe and effective agent for therapy of typhoid fever.

Clinical and pharmacokinetic study of cefotetan in biliary tract infections: preliminary report.

Twelve hospitalised patients, affected by biliary tract infections, were treated with cefotetan at dosages ranging between 4 and 6 g daily i.v. In only 11 patients was the aetiological agent identified. Eleven patients (91.67%) completely recovered from their infections and the pathogens were eradicated; the treatment failed in only 1 patient (8.33%). Furthermore, determinations were made of cefotetan concentrations in serum, gallbladder bile, gallbladder wall and gallstones of 14 patients undergoing cholecystectomy: in 7 patients after only 1 injection i.v. of 2 g and in 7 patients after 7 injections i.v. of 2 g at intervals of 12 h. The levels recorded were several times higher than the minimum inhibitory concentrations against bacteria that are most often responsible for biliary infections. Cefotetan is a promising and effective antimicrobial agent in the therapy of biliary tract infections.