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.

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.

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.

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.

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.

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.

[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%.

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.

Aztreonam in the therapy of nosocomial infections in patients with impaired host defenses.

A clinical trial was carried out to evaluate the effectiveness of treatment with aztreonam in hospital-acquired infections. Twenty patients (13 men and 7 women) with impaired host defenses and nosocomial infections were treated with aztreonam at a dosage ranging 4 and 6 g/day I.V. at 8 or 12-hour intervals. Average length of therapy was 10.35 +/- 4.61 days. The isolated organisms were as follows: Escherichia coli (5), Pseudomonas aeruginosa (5), Klebsiella pneumoniae (3), Enterobacter cloacae (1), Proteus mirabilis (2), Proteus vulgaris (1), Acinetobacter anitratus (1), Serratia marcescens (1), Citrobacter freundii (1), Bacteroides fragilis (3), Bacteroides melaninogenicus (1). In 5 patients (25%) a mixed infection was observed. Sixteen patients (80%) were completely cured from infection and 24 isolated organisms (88.8%) were eradicated. No adverse reactions were observed. Aztreonam has undoubtedly high clinical and bacteriological efficacy in the therapy of nosocomial infections in patients with impaired host defenses.

Cefamandole concentrations in the anterior chamber of the eye in rabbits and humans.

Cefamandole concentrations were determined in the aqueous humor of the anterior chamber of the eye in 10 rabbits and in 15 patients undergoing cataract extraction. The rabbits received 50 mg of cefamandole per kilogram of body weight in the ear vein and humans received 2 g of cefamandole by intravenous injection before operation. The levels recovered were several times higher than the minimum inhibitory concentrations (MICs) against the bacteria that are most often responsible for ocular infections.

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.

[Evaluation of monoamine oxidase in the serum (SMAO) of clinically healthy volunteers]. / Valutazione delle monoamino-ossidasi del siero (SMAO) in soggetti clinicamente sani.

Linearity of response "day-to-day" and "within-day" variation of a simple method for serum monoaminoxidase (SMAO) activity have been evaluated. SMAO determination in 209 clinically healthy subjects was performed to find out the "reference values" for the method.

[Activity of serum monoamine oxidase (SMAO) in patients with connective tissue diseases : preliminary results]. / Comportamento delle monoamino-ossidasi del siero (SMAO) in pazienti con affezioni connettivitiche :risultati preliminari.

Serum monoaminoxidase activity (SMAO) has been determined in patients with different connective tissue diseases. Preliminary results show a constant and significative increase sclerosis.

Cefotaxime (HR-756) in urinary tract infections.

A total of 30 hospitalized patients with upper and lower urinary tract infections were treated with cefotaxime (HR-756) by intramuscular or intravenous route. All patients had a monomicrobial infection, and the major part of bacterial isolates were gram-negative bacilli (83%) while gram-positive cocci accounted only for 17%. In 83% of the cefotaxime-treated patients both the bacteria and symptoms were eliminated at the 2nd week of follow-up, while failure or relapse occurred in 17% of the patients. No reinfections were recorded. Cefotaxime was a safe and well-tolerated drug and can be considered as an effective antibiotic in the therapy of urinary tract infections caused by "difficult' gram-negative bacilli.

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.

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 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.