Prospective Study of Antibiotic Prophylaxis for Prostate Biopsy Involving >1100 Men

We aimed to compare infection rates for two 3-day antibiotic prophylaxis regimens for transrectal ultrasound-guided prostate biopsy (TRUSgbp) and demonstrate local microbiological trends. In 2008, 558 men and, in 2009, 625 men had TRUSgpb. Regimen 1 (2008) comprised 400 mg Ofloxacin immediately before biopsy and 200 mg 12-hourly for 3 days. Regimen 2 (2009) comprised Ofloxacin 200 mg 12-hourly for 3 days commencing 24 hours before biopsy. 20/558 (3.6%) men had febrile episodes with regimen 1 and 10/625 (1.6%) men with regimen 2 (P = 0.03). E. coli was the most frequently isolated organism. Overall, 7/13 (54%) of positive urine cultures were quinolone resistant and (5/13) 40% were multidrug resistant. Overall, 5/9 (56%) patients with septicaemia were quinolone resistant. All patients were sensitive to Meropenem. There was 1 (0.2%) death with regimen 1. Commencing Ofloxacin 24 hours before TRUSgpb reduced the incidence of febrile episodes significantly. We observed the emergence of quinolone and multidrug-resistant E. coli. Meropenem should be considered for unresolving sepsis

Characteristics of gram-negative urinary tract infections caused by extended spectrum beta lactamases: pivmecillinam as a treatment option within South Dublin, Ireland

Abstract Background The prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is increasing and the therapeutic options are limited, especially in primary care. Recent indications have suggested pivmecillinam to be a suitable option. This pilot study aimed to assess the viability of pivmecillinam as a therapeutic option in a Dublin cohort of mixed community and healthcare origin. Methods A prospective measurement of mean and fractional inhibitory concentrations of antibiotic use in 95 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae was carried out. 36 % patients were from general practice, 40 % were admitted to hospital within south Dublin, and 25 % samples arose from nursing homes. EUCAST breakpoints were used to determine if an isolate was sensitive or resistant to antibiotic agents. Results Sixty-nine percent of patients (N = 66) with urinary ESBL isolates were female. The mean age of females was 66 years compared with a mean age of 74 years for males. Thirty-six percent of isolates originated from primary care, hospital inpatients (26 %), and nursing homes (24 %). The vast majority of ESBL isolates were E. coli (80 %). The E tests for mecillinam and co-amoxiclav had concentration ranges from 0.16 mg/L up to 256 mg/L. The mean inhibitory concentration (MIC) of mecillinam ranged from 0.25 to 256 mg/L, while co-amoxiclav MICs ranged from 6 to 256 mg/L. The percentage of isolates resistant to mecillinam and co-amoxiclav was found to be 5.26 and 94.74 % respectively. Conclusions This is the first study exploring the use of pivmecillinam in an Irish cohort and has demonstrated that its use in conjunction with or without co-amoxiclav is an appropriate and useful treatment for urinary tract infections caused by ESBL-producing organisms

Patient demographics.

<p>^a Healthcare-associated infections were defined as (i) index positive blood culture collected ≥48hrs after hospital admission, and no signs or symptoms of the infection noted at time of admission; OR (ii) index positive blood culture collected <48hrs after hospital admission if any of the following criteria are met: received intravenous therapy in an ambulatory setting in the 30 days before onset of BSI, attended a hospital clinic or haemodialysis in the 30 days before onset of BSI, hospitalised in an acute care hospital for ≥ 2 days in the 90 days prior to onset of BSI, resident of nursing home or long-term care facility.</p><p>^b<i>Staphylococcus aureus</i> bacteraemia was defined as uncomplicated if all of the following criteria were met: exclusion of endocarditis; no evidence of metastatic infection; absence of implanted prostheses; follow-up blood cultures at 2–4 days culture-negative for <i>S</i>. <i>aureus</i>; defervescence within 72 h of initiating effective therapy. Percentages shown are of entire <i>S</i>. <i>aureus</i> BSI population.</p><p>^† Three patients had chronic diabetic foot ulcers as a source of their <i>S</i>. <i>aureus</i> BSI, and in all cases the contiguous underlying bone was also found to be infected.</p><p>MRSA = methicillin-resistant <i>Staphylococcus aureus</i>. NA = not applicable. BSI = bloodstream infection.</p><p>Data are displayed as median (interquartile range) and number (percentage). <i>P</i> values are calculated by Mann-Whitney and Fisher’s exact test respectively.</p

Prior exposure to <i>S</i>. <i>aureus</i> increases IFNγ secretion by CD4⁺ and CD8⁺ T cells during subsequent infection.

<p>Groups of mice were exposed to <i>S</i>. <i>aureus</i> (5x10⁸ CFU) via an i.p. injection on d 0, 7 and 14. Prior exposed mice were then re-challenged with an i.p. injection of <i>S</i>. <i>aureus</i> (5x10⁸ CFU) on d 35 alongside a control group of naïve mice. At indicated time points post-challenge the peritoneal cavity was lavaged with PBS to assess IFNγ secretion by ELISA (A). n = 15 per group. At 3 h post challenge peritoneal cells were isolated to assess the proportions of IFNγ-producing CD4⁺ and CD8⁺ T cells using flow cytometry (B). Results expressed as mean ± SEM and representative FACS plots. n = 5 per group. *p<0.05, **p<0.005, ***p<0.001.</p

Human <i>S</i>. <i>aureus</i> bloodstream infection induces <i>S</i>. <i>aureus</i> antigen-specific effector memory Th1 cells and anti-ClfA antibodies.

<p>PBMCs were isolated from patients, CFSE-labelled and incubated with heat-killed <i>S</i>. <i>aureus</i> PS80 strain (1μg/ml ≈ 1x10⁷ CFU/ml) or media alone for 10 d. Proportions of <i>S</i>. <i>aureus</i> antigen-specific effector memory cells were assessed by gating on IFNγ⁺CD45RO⁺ cells in the CFSE_lo CD4⁺ population (A). For each patient, media only responses were subtracted from responses to heat-killed <i>S</i>. <i>aureus</i> to determine the antigen-specific response. n = 5–12 per group. IgG antibody binding to ClfA was measured in patient sera using a bead-based flow cytometry technique (B). n = 11–24 per group. Results shown as box-and-whiskers plots where the horizontal line indicates the median, boundaries of the box the IQR, and whiskers indicate the highest and lowest values of the results, and representative FACS plots of CD4⁺CFSE_lo cells (A). SA = <i>S</i>. <i>aureus</i>, EC = <i>E</i>. <i>coli</i>, BSI = bloodstream infection. * p<0.05.</p

Human <i>S</i>. <i>aureus</i> bloodstream infection is associated with increased IFNγ production.

<p>Serum from <i>S</i>. <i>aureus</i> and <i>E</i>.<i>coli</i> bloodstream infection patients was collected on day 7 ± 2 post-initial bacteraemia and assessed for IFNγ (A) and IL-17A (B) by ELISA. Results expressed as individual patient values with median indicated by bar, n = 11–24 per group. *p<0.05.</p

Vaccine-induced type 1 immunity protects against <i>S</i>. <i>aureus</i> infection.

<p>Mice were vaccinated with CpG (50μg/mouse), ClfA (1μg/mouse), or CpG+ClfA via s.c. injection on d 0, 14 and 28. On d 63 mice were challenged with <i>S</i>. <i>aureus</i> (5x10⁸ CFU) via i.p. injection alongside a control group of sham-immunised (with PBS) mice. At 72 h post-infection, bacterial burden was assessed in the peritoneal cavity, kidneys and spleen. Results expressed as log₁₀ CFU/ml with means indicated by bars. n = 5–10 per group. **p<0.005, ***p<0.001.</p

Transfer of <i>S</i>. <i>aureus</i> antigen-specific peritoneal Th1 cells protects against subsequent <i>S</i>. <i>aureus</i> infection via enhanced macrophage responses.

<p>Groups of mice received transfers of 5x10⁶<i>S</i>. <i>aureus</i> specific Th1 cells originating from the peritoneal cavity of previously exposed mice via i.p. injection. Another group of mice received a transfer of 5x10⁶ naive splenic CD3⁺ cells as a control. At 3 h post transfer both groups of mice were challenged with <i>S</i>. <i>aureus</i> (5x10⁸ CFU) via i.p. injection. At 72 h post-bacterial challenge the bacterial burden was assessed in the peritoneal cavity, kidneys and spleen (A). Results expressed as log₁₀ CFU/ml with mean indicated by bars. At indicated time points post-bacterial challenge, the peritoneal cavity was lavaged with PBS to assess CXCL1 and CCL5 secretion by ELISA (B,C). Results expressed as mean ± SEM. At indicated time points post-challenge, the absolute numbers of macrophages (F4/80⁺Ly6G^-) were assessed in the peritoneal cavity by flow cytometry (D). MHCII expression by infiltrating macrophages was determined 24 h post infection (E). Absolute numbers of neutrophils (Ly6G⁺CD11b⁺) in the peritoneal cavity were assessed at the indicated time points post-challenge (F). Results expressed as mean ± SEM. n = 5–8 mice per group. Data pooled from 3 independent experiments. *p<0.05, **p<0.005.</p