Clinical characteristics of peripheral venous catheter-associated gram-negative bloodstream infection among patients with malignancy.

PURPOSE: Previous studies have suggested that peripheral venous catheter is a significant source of gram-negative bacteraemia in patients with malignancy. We aimed to identify risk factors and develop a clinical prediction rule for the involvement of gram-negative organisms in peripheral venous catheter-associated bloodstream infections (PVC-BSIs) among patients with malignancy. METHODS: This retrospective cohort study was conducted at a 700-bed cancer hospital in Japan. Consecutive patients diagnosed with PVC-BSI based on clinical and microbiological criteria were included in this study. Based on clinical and microbiological characteristics of PVC-BSIs in cancer patients, a logistic regression model for predicting gram-negative organisms as causative organisms in PVC-BSIs was then developed. RESULTS: Of the 99 patients included in our cohort, 60 patients (60.6%) had gram-negative PVC-BSIs. The median age of patients with PVC-BSIs was 67 years (interquartile range [IQR], 59-74 years), and the median Pitt bactearemia score was 1 (IQR, 0-3). The median duration of catherization was 5 days (IQR, 4-7 days) and 70 patients (70.7%) received peripheral parenteral nutrition that contained amino acids. On multivariable analysis, age ≥65 years (odds ratio [OR], 3.07; 95% confidence interval [CI], 1.10-8.62), showering (OR, 3.15; 95% CI, 1.07-9.26), Pitt bacteraemia score ≥2 points (OR, 6.96; 95% CI, 2.52-19.2), and use of peripheral parenteral nutrition (OR, 0.31; 95% CI, 0.10-0.98) were independent predictors for gram-negative PVC-BSIs among all PVC-BSIs. The simplified PVC-GN scores established to predict gram-negative PVC-BSIs had a optimism-corrected c-index of 0.775. CONCLUSION: Gram-negative bacteria were more commonly responsible for PVC-BSI than Gram-positive bacteria among cancer patients in this cohort. Involvement of Gram-negative bacteria in PVC-BSIs could be predicted with readily available clinical variables.

[Antimicrobial susceptibilityof clinical isolates of aerobic gram-negative bacteria in 2008].

We determined MICs of antibacterial agents against 1145 clinical strains of aerobic Gram-negative bacteria (22 species) isolated at 16 Japanese facilities in 2008. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.8% of Escherichia coli, 2.6% of Klebsiella pneumoniae, 6.8% of Klebsiella oxytoca, 5.5% of Proteus mirabilis and 1.8% of Proteus vulgaris. ESBL produced strains were 6.8% at K. oxytoca that increased compared with 3.2% and 5.5% at P. mirabilis that decreased compared with 18.8% in 2006. Among Haemophilus influenzae, 61.7% that decreased compared with 67.7% in 2006, equaled 58.7% in 2004, were strains when classified by penicillin-binding protein 3 mutation. Against Pseudomonas aeruginosa, the activity of most antibacterial agents was similar to that in 2006. Although two antibacterial agents that tobramycin showed an MIC90 of 1 microg/mL and doripenem showed an MIC90 of 4 microg/mL against P. aeruginosa have potent activity. Of all P. aeruginosa strains, 4.3% were resistant to six agents of nine antipseudomonal agents, that decreased compared to 12.2% in 2004 and 5.7% in 2006. Against other glucose-non-fermentative Gram-negative rods, the activity of most antibacterial agents was similar to that in 2006.

[Antimicrobial susceptibility of clinical isolates of aerobic gram-positive cocci and anaerobic bacteria in 2008].

The activity of antibacterial agents against aerobic Gram-positive cocci (25 genus or species, 1029 strains) and anaerobic bacteria (21 genus or species, 187 strains) isolated from clinical specimens in 2008 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis was 59.6% and 81.2%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM), linezolid (LZD) and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC90s of < or = 2 microg/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 92.0% that was highest among our previous reports. Cefpirome, carbapenems, VCM, teicoplanin (TEIC), LZD and QPR/DPR had MIC90s of < or = 1 microg/mL against PC-intermediate and resistant S. pneumoniae strains. Against all strains of Enterococcus faecalis and Enterococcus faecium, the MICs of VCM and TEIC were under 2 microg/mL, and no resistant strain was detected, suggesting that these agents had excellent activities against these species. 15.9% of E. faecalis strains and 1.2% of E. faecium strains showed intermediate to LZD. 17.1% of E. faecium strains showed intermediate or resistant to QPR/DPR. Against all strains of Clostridium difficile, the MIC of VCM was under 1 microg/mL, suggesting that VCM had excellent activity. Carbapenems showed good activity against Clostridiales, Bacteroides spp., and Prevotella spp., but one strain of Bacteroides fragilis showed resistant to carbapenems. And so, the susceptibility of this species should be well-focused in the future at detecting continuously.

[Antimicrobial susceptibility of clinical isolates of aerobic Gram-positive cocci and anaerobic bacteria in 2006].

The activity of antibacterial agents against aerobic Gram-positive cocci (26 species, 1022 strains) and anaerobic bacteria (23 species, 184 strains) isolated from clinical specimens in 2006 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis was 53.0% and 65.8%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM) and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC90s of < or = 2 micrcog/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 87.6%. Ceftriaxone, cefpirome, cefepime, carbapenem antibiotics, VCM, teicoplanin, linezolid(LZD) and QPR/DPR had MIC90s of < or = 1 microg/mL against PC-intermediate and resistant S. pneumoniae strains. Against all strains of Enterococcus faecalis and Enterococcus faecium, the MICs of VCM and TEIC were under 2 microg/mL, and no resistant strain was detected, suggesting that these agents had excellent activities against these species. 10.9% of E. faecalis strains or 3.5% of E. faecium strains showed intermediate or resistant to LZD. 24.4% of E. faecium strains showed intermediate or resistant to QPR/DPR. Against all strains of Clostridium difficile, the MIC of VCM were under 1 microg/mL, suggesting that VCM had excellent activity against C. difficile. Carbapenems showed good activity against Peptococcaceae, Bacteroides spp., and Prevotella spp. However since several strains of Bacteroides fragilis showed resistant to carbapenems and the susceptibility of this species should be well-focused in the future.

[Antimicrobial susceptibility of clinical isolates of aerobic Gram-negative bacteria in 2006].

We determined MICs of antibacterial agents against 1280 clinical strains of aerobic Gram-negative bacteria (19 genus or species) isolated at 16 Japanese facilities in 2006. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.7% of Escherichia coli, 2.7% of Klebsiella spp., and 11.4% of Proteus spp. Notably, 18.8% of Proteus mirabilis was found to produce ESBL higher than 16.7% in 2004. This result was higher extremely than other species. Among Haemophilus influenzae, only 1.2% produced beta-lactamase and 62.8% that increased compared with 57.7% in 2004, were beta-lactamase-negative ampicillin-resistant strains when classified by penicillin-binding protein 3 mutation. Although few antibacterial agents against Pseudomonas aeruginosa have potent activity, only three agents--doripenem, ciprofloxacin, and tobramycin-showed an MIC90 of 4 microg/mL. Of all P aeruginosa strains, 5.7% were resistant to six or more agents of nine antipseudomonal agents, a decrease compared to 8.7% in 2004. Against other glucose-non-fermentative Gram-negative bacteria, the activity of most antibacterial agents was similar to that in 2004.

Microbiological and clinical study of methicillin-resistant Staphylococcus aureus (MRSA) carrying VraS mutation: changes in susceptibility to glycopeptides and clinical significance.

The VraSR two-component regulatory system is involved in glycopeptide resistance in Staphylococcus aureus. We examined the relationship between VraS mutation and susceptibility to various antimicrobial agents in 400 clinical isolates of methicillin-resistant S. aureus (MRSA) from Cancer Institute Hospital between 1998 and 2004. The prevalence of MRSA isolates with teicoplanin minimum inhibitory concentrations (MICs) of 4-8 microg/mL rose between 2000 and 2002 (52% in 2000). Among the isolates displaying reduced susceptibility to teicoplanin (78 isolates), 99% harboured the Ile5Asn (I5N) mutation in VraS. In addition, MICs of oxacillin and imipenem tended to be higher for I5N mutants compared with those for non-I5N isolates. By contrast, no significant change was noted in susceptibility to arbekacin or vancomycin. In this hospital, I5N mutants emerged at an early stage after the introduction of teicoplanin and thereafter declined in number upon increased usage of arbekacin instead of glycopeptides. Outcomes from 18 patients who were infected with MRSA with reduced susceptibility to teicoplanin were analysed microbiologically in a retrospective manner. Teicoplanin was effective in 50% of the patients treated with this drug. On the other hand, arbekacin and vancomycin were effective in all cases. The results indicate the relationship between antimicrobial susceptibility and therapeutic effect.

[In-vitro susceptibilites to levofloxacin and various antibacterial agents of 18,639 clinical isolates obtained from 77 centers in 2004].

A total of 18,639 clinical isolates in 19 species collected from 77 centers during 2004 in Japan were tested for their susceptibility to fluoroquinolones (FQs) and other selected antibiotics. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae showed a high susceptible rate against FQs. The isolation rate of beta lactamase non-producing ampicillin-resistant H. influenzae was approximately three times as large as those of western countries. Most strains of Enterobacteriaceae were also susceptible to FQs. The resistance rate of Escherichia coli against FQs has however been rapidly increasing so far as we surveyed since 1994. The FQs-resistant rate in methicillin-resistant Staphylococcus aureus (MRSA) showed approximately 90% except for 36%. of sitafloxacin while FQs-resistant rate in methicillin-susceptible S. aureus (MSSA) was around 5%. The FQs-resistant rate of methicillin-resistant coagulase negative Staphylococci (MRCNS) was also higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), however, it was lower than that of MRSA. In Pseudomonas aeruginosa clinical isolates, 32-34% from UTI and 15-19% of from RTI was resistant to FQs. Acinetobacter spp. showed a high susceptibility to FQs. Although FQs-resistant Neisseria gonorrhoeae have not been increased in western countries, it is remarkably high in Japan. In this survey, isolates of approximately 85% was resistant to FQs.

[In vitro susceptibilites to levofloxacin and various antibacterial agents of 11,475 clinical isolates obtained from 52 centers in 2002].

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.

[Sensitivity of MRSA isolated in our hospital to various antibacterial agents: changes over 5 years].

Among methicillin resistant Staphylococcus aureus (MRSA) strains isolated from clinical specimens during 5 years period from 1998 through 2002 in Cancer Institute Hospital, Japanese Foundation for Cancer Research, a total of 100 strains, one per patient, were successively selected each year, and their sensitivity to various antibacterial agents was measured to assess changes over five years in their sensitivity to these drugs. The following results were obtained. 1. Little or no change was observed in the sensitivity to arbekacin during 5 years period. In contrast, a tendency toward decreased sensitivity was observed with vancomycin and teicoplanin, with the tendency more marked with the latter agent. 2. Arbekacin, vancomycin and teicoplanin inhibited the growth of all clinical isolates in the year 2002 at 3.13, 1.56 and 12.5 microg/mL, respectively. 3. The sensitivity to netilmicin tended to decrease over the years. 4. Minocycline, imipenem and ofloxacin had little or no antibacterial activity, with MIC50 of more than 12.5 microg/mL throughout the years studied. 5. Ninety five percent of MRSA strains isolated during the five years were classified as coagulase type II, and enterotoxins were found to be type C in 51% and type AC in 17% of the strains studied.