Impact of a hospital-wide antibiotic restriction policy program on the resistance rates of nosocomial Gram-negative bacteria.

BACKGROUND: To evaluate the impact of an antibiotic restriction policy on antibiotic consumption and Gram-negative resistance rates, in an environment of antibiotic overconsumption and increasing resistance rates for nosocomial pathogens. METHODS: The study was a 'before and after' trial of 18-month duration; the antibiotic restriction policy program was implemented in 1998-2000 and was based on a government program addressed by the Ministry of Health to public hospitals on a national basis. This included prescribing of all newer antibiotics on an order form, auditing of the order forms and consultation with infectious diseases (ID) specialists, dispensing of treatment and prophylaxis guidelines, feedback, and face-to-face education. Antibiotic consumption and Gram-negative resistance rates were recorded before and after the intervention. RESULTS: Despite the addition of a new 40-bed ID department in the hospital during the 'after' period, the consumption of restricted antibiotics was significantly reduced by 42% (and their cost by 31%). Gram-negative resistance rates for Pseudomonas, Klebsiella, and Enterobacter, serving as index microorganisms for Gram-negative nosocomial pathogens, were significantly reduced during the 'after' period, even against antibiotics for which there was an increase in consumption. CONCLUSIONS: Multidisciplinary restriction programs can reduce antibiotic consumption and Gram-negative resistance rates in the hospital setting.

Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor.

INTRODUCTION: Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed. METHODS: A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden. RESULTS: Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥ 17 and suPAR ≥ 12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12 ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR ≥ 12 ng/ml with mortality 17.4%; iii) APACHE II ≥ 17 and suPAR <12 ng/ml with mortality 37.4%; and iv) APACHE II ≥ 17 and suPAR ≥ 12 ng/ml with mortality 51.7%. This prediction rule was confirmed by the Swedish cohort. CONCLUSIONS: A novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR is proposed. Prognostication by this rule is confirmed by an independent cohort.

Changes in adaptive and innate immunity in patients with acute pancreatitis and systemic inflammatory response syndrome.

BACKGROUND: Acute pancreatitis is a form of inflammation with clinical features ranging from pancreatic inflammation to fatal systemic manifestations. The aim of this study was to clarify changes in lymphocyte subsets and alterations in the functioning of natural killer (NK) cells. PATIENTS AND METHODS: Forty-five patients were enrolled into the study; 35 with acute pancreatitis and systemic inflammatory response syndrome (SIRS) and 10 healthy subjects. Blood was sampled early from all patients. Blood immune cells were studied on days 1 and 4 by flow cytometry. Tumor necrosis factor-α (TNFα) and interleukin (IL)-6 were estimated from supernatants of NK cells before/after stimulation with lipopolysaccharide (LPS). RESULTS: Apoptosis in patients was significantly different on days 1 and 4 compared with controls. Apoptosis of CD4(+) lymphocytes was significantly correlated with the days to resolution of SIRS (r = +0.586, p = 0.022). Significant differences were observed in TNFα and IL-6 on day 1 with/without LPS stimulation between patients and healthy individuals. Significantly increased levels of TNFα and IL-6 were found after LPS stimulation compared with unstimulated supernatants in day 1. CONCLUSION: NK cells altered their secretory status when stimulated with LPS. This finding could be explained by the cellular reprogramming of NK cells in the field of acute pancreatitis and SIRS.

The significance of compliance for the success of antimicrobial prophylaxis in recurrent lower urinary tract infections: the Greek experience.

In an attempt to define the most important driver responsible for recurrence of cystitis in women, 181 records were retrospectively analysed among 1010 consecutive references in a tertiary centre for lower urinary tract infections (UTIs). All 181 women had more than three episodes of cystitis per year; 129 were under continuous prophylaxis and 52 were under postcoital prophylaxis. Analysis revealed that the most important factor affecting successful outcome of chemoprophylaxis was the compliance of patients (odds ratio 0.074; P<0.0001). Among women treated for >or=6 months, the most effective regimen was nitrofurantoin, with a success rate of 96.8% compared with 82.8% for trimethoprim/sulphamethoxazole and 72.3% for norfloxacin (P=0.046 between agents). Failure of chemoprophylaxis was observed in 51 women in total; in 26 of them resistance to the administered agent had developed. Results of this retrospective study revealed that the most important driver leading to failure of prophylaxis for recurrent lower UTIs was the lack of compliance of women with their medication. Nitrofurantoin was the most potent among the administered agents.

Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women.

One hundred sixty-three women with uncomplicated acute lower urinary tract infections were included in a multicenter randomized study comparing cefpodoxime-proxetil (one 100-mg tablet twice daily) with trimethoprim-sulfamethoxazole (one double-strength tablet [160/800 mg] twice daily) for 3 days. A total of 30 women in both arms were excluded from the study for various reasons. At 4 to 7 days after the discontinuation of therapy, 62 of 63 (98.4%) cefpodoxime-proxetil recipients and 70 of 70 (100%) trimethoprim-sulfamethoxazole patients were clinically cured and demonstrated bacteriological eradication, respectively. At 28 days after treatment, 48 of 55 (87.3%) and 43 of 50 (86%) cefpodoxime-proxetil recipients as well as 51 of 60 (85%) and 42 of 50 (84%) trimethoprim-sulfamethoxazole recipients were clinically cured and demonstrated bacteriological eradication, respectively. Independently of the prescribed regimen, a significant difference (P < 0.001) in failure rates was observed only for patients with a previous history of three or more episodes of acute cystitis per year. With the exception of one patient in the trimethoprim-sulfamethoxazole arm who discontinued therapy because of gastrointestinal pain, both antimicrobials were well tolerated. In conclusion, cefpodoxime-proxetil treatment for 3 days was as safe and effective as trimethoprim-sulfamethoxazole for 3 days for the treatment of uncomplicated acute cystitis in women.

Bacterial translocation following intrabdominal surgery. Any influence of antimicrobial prophylaxis?

Bacterial translocation may accompany various intra-abdominal operations. In order to define its incidence and the effect of preoperative antimicrobial prophylaxis and the duration of hospitalization before elective surgery, mesenteric lymph nodes were excised from 43 patients undergoing various programmed intra-abdominal operations without any evidence of intra-abdominal septic focus. Nodes were cultured and examined for histopathological findings of reactive lymphadenitis. The incidence of bacterial translocation was 5.9% accompanying graft replacement post aortic aneurysm, 44.4% accompanying colectomy, 50% accompanying gastrectomy and 33.3% accompanying splenectomy but it did not occur with other types of laparotomy. Bacterial isolates from the mesenteric lymph nodes were mainly species of enterobacteriaceae. Bacterial translocation was found in 17.6% of patients receiving antimicrobial prophylaxis prior to dissection of the lymph nodes compared with 26.8% of those administered prophylaxis after lymph node removal (PNS). Reactive lymphadenitis was documented in 70.6% of patients undergoing aortic aneurysm graft replacement, in 33.3% undergoing colectomy, in 50% undergoing gastrectomy, in 33.3% undergoing cholocystectomy (33.3%) whereas it was not found in any patient undergoing splenectomy or other type of laparotomy. It is concluded that colectomy and gastrectomy are accompanied by the greatest risk for bacterial translocation among a great variety of intra-abdominal operations. The administration of preoperative antimicrobial prophylaxis and the duration of hospitalization before operation did not seem to have any effect on the process of bacterial translocation.

Procalcitonin: a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient?

OBJECTIVES: To define the role of procalcitonin in the differential diagnosis, prognosis and follow-up of critically ill patients. DESIGN: Prospective study during the 2-year period from January 1998-2000. PATIENTS: One hundred nineteen critically ill patients: 29 with systemic inflammatory response syndrome (SIRS) without any signs of infection, 11 with sepsis, 17 with severe sepsis, 10 with septic shock and 52 controls. Daily measurements of procalcitonin were performed by an immunocheminoluminometric assay, and values were correlated to the clinical characteristics of the patients. RESULTS: Mean concentrations of procalcitonin were 5.45 (95% CI: 2.11, 8.81), 7.29 (95% CI: -1.92,14.59), 6.26 (95% CI: -1.32, 13.85) and 38.76 ng/ml (95% CI: 0.15, 77.38) on the 1st day in patients with SIRS, sepsis, severe sepsis and septic shock, respectively, and were statistically superior to those of control patients. Procalcitonin was gradually diminished over time with the resolution of the syndrome, while it was sustained in the same or more augmented levels upon worsening. Mean concentrations of procalcitonin on the 1st day for patients finally progressing to ARDS, to ARDS and acute renal failure, to ARDS, acute renal failure and DIC and to ARDS, acute renal failure, DIC and hepatic failure were 10.48, 8.08, 32.72 and 43.35 ng/ml, respectively. ROC curves of the sensitivity and specificity of procalcitonin for the evaluation of SIRS and sepsis were similar. CONCLUSIONS: The definite differential diagnosis between SIRS and sepsis may not rely on a single application of procalcitonin but on the complete clinical and laboratory evaluation of the patient with procalcitonin playing a considerable role. Procalcitonin is an early prognostic marker of the advent of MODS; therefore, daily determinations might help in the follow-up of the critically ill patient.