Rotation of antimicrobial therapy in the intensive care unit: impact on incidence of ventilator-associated pneumonia caused by antibiotic-resistant Gram-negative bacteria.

The development of antibiotic resistance is associated with high morbidity and mortality, particularly in the intensive care unit (ICU) setting. We evaluated the effect of an antibiotic rotation programme on the incidence of ventilator-associated pneumonia (VAP) caused by antibiotic-resistant Gram-negative bacteria. We conducted a 2-year before-and-after study at two medical-surgical ICUs at two different tertiary referral hospitals. We included all mechanically ventilated patients admitted for > or =48 h who developed VAP. From 1 January through 31 December 2007, a quarterly rotation of antibiotics (piperacillin/tazobactam, fluoroquinolones, carbapenems and cefepime/ceftazidime) for the empirical treatment of VAP was implemented. We analysed the incidence of VAP and the antibiotic resistance patterns of the responsible pathogens in 2006, before (P1) and, in 2007, after (P2) the introduction of the scheduled rotation programme. Overall, there were 79 VAP episodes in P1 and 44 in P2; the mean incidence of VAP was 20.96 cases per 1,000 days of mechanical ventilation (MV) during P1 and 14.97 in P2, with no significant difference between periods on segmented regression analysis. We observed a non-significant reduction of the number of both the poly-microbial (14 [17.7%] in P1 and 5 [10.6%] in P2 [p = 0.32]) and of the antibiotic-resistant Gram-negative bacteria-related VAP (42 [45.2%] in P1 and 16 [34%] in P2 [p = 0.21]). Conversely, the number of VAP caused by Pseudomonas aeruginosa passed from 8.35 per 1,000 days of MV in P1 to 2.33 per 1,000 days of MV in P2 (p = 0.02). No difference in ICU mortality and crude in-hospital mortality between P1 and P2 was noted. Moreover, no significant change of microbial flora isolated through clinical cultures was observed. We were able to conclude that, despite global microbial flora not being affected by such a programme, antibiotic therapy rotation may reduce the incidence of VAP caused by antibiotic-resistant Gram-negative bacteria in the ICU, such as Pseudomonas aeruginosa. The application of this programme may also improve antibiotic susceptibility. However, further studies are needed to confirm our results.

Meticillin-resistant Staphylococcus aureus control in an intensive care unit: a 10 year analysis.

Data regarding the efficacy of programmes to control meticillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs) are limited. We performed an observational 'before-and-after' study to evaluate the search-and-destroy (S&D) strategy as compared with S&D and isolation (SDI), to control MRSA in a general ICU. S&D included active surveillance, contact precautions and treatment of carriers; in SDI, isolation or cohorting were added. Three phases were identified: period 1 (p1), 1996-1997, before the introduction of programme; period 2 (p2), 1998-2002, with S&D programme; period 3 (p3), 2003-2005, with SDI in a new ICU. During the 10 years of the study we observed 3978 patients; 667, 1995 and 1316 patients in p1, p2 and p3 respectively. The numbers of MRSA-infected patients were 19 in p1, 23 in p2, and 6 in p3. The infection rate was 3.5, 1.7 and 0.7 cases per 1000 patient-days in p1, p2 and p3, respectively; a significant reduction was observed between p1 vs p2 (P=0.024) and p2 vs p3 (P=0.048), although the latter was not confirmed by a segmented regression analysis. The proportion of ICU-acquired MRSA cases was 80%, 77% and 52% during p1, p2 and p3, respectively (P=0.0001 for trend). The proportion of S. aureus isolates resistant to meticillin was 51%, 32% and 23% during p1, p2 and p3, respectively (P<0.0001 for trend). S&D strategy was effective in significantly reducing MRSA infection, transmission rates and proportion of meticillin resistance in an ICU with endemic MRSA. SDI may further enhance S&D efficacy.

Antibiotic prophylaxis of early onset pneumonia in critically ill comatose patients. A randomized study.

OBJECTIVE: To evaluate if a 3-day ampicillin-sulbactam prophylaxis can reduce the occurrence of early-onset pneumonia (EOP) in comatose mechanically-ventilated patients. DESIGN: This was a single-centre, prospective, randomised, open study. SETTING: A 10-bed general-neurological ICU in a 2,000-bed university hospital. PATIENTS AND PARTICIPANTS: Comatose mechanically-ventilated patients with traumatic, surgical or medical brain injury. INTERVENTIONS: Patients were randomized to either ampicillin-sulbactam prophylaxis (3 g every 6 h for 3 days) plus standard treatment or standard treatment alone. MEASUREMENTS AND RESULTS: Main outcome was the occurrence of EOP. Secondary outcome measures were occurrence of late-onset pneumonia, percentage of non-pulmonary infections and of emerging multiresistant bacteria, duration of mechanical ventilation and of ICU stay and ICU mortality. Interim analysis at 1 year demonstrated a statistically significant reduction of EOP in the ampicillin-sulbactam group, and the study was interrupted. Overall, 39.5% of the patients developed EOP, 57.9% in the standard treatment group and 21.0% in the ampicillin-sulbactam group (chi-square 5.3971; P =0.022). Relative risk reduction of EOP in patients receiving ampicillin-sulbactam prophylaxis was 64%; the number of patients to be treated to avoid one episode of EOP was three. No differences in other outcome parameters were found; however, the small sample size precluded a definite analysis. CONCLUSIONS: Antibiotic prophylaxis with ampicillin-sulbactam significantly reduced the occurrence of EOP in critically ill comatose mechanically ventilated patients. This result should encourage a large multicenter trial to demonstrate whether ampicillin-sulbactam prophylaxis reduces patient mortality, and whether antibiotic resistance is increased in patients receiving prophylaxis.

Free radical-induced lipoperoxidation and severe head injury. A clinical study.

Ten severely head injured patients (GCS less than or equal to 8), aged 17-62 years, were studied in order to investigate the role of lipoperoxidation in secondary brain damage. No patients had intracranial mass lesions, shock, hypoxemia, fever or sepsis. Blood samples were taken from the jugular bulb and from the right atrium, and thiobarbituric acid reacting substances (TBARS) were measured in plasma by spectrophotometry. Arterio-jugular venous oxygen differences (AVDO2) were obtained in seven patients, in order to estimate cerebral blood flow. Jugular TBARS (TBARSj) were always elevated (from To, to 2 h after injury) and correlated in a linear fashion with TBARS of right atrium (TBARSv): r = 0.74, p less than 0.001. TBARSj and AVDO2 are closely correlated, in accordance with an exponential function (R = 0.45, p less than 0.001) which describes how any cerebral perfusion derangement determines high levels of TBARSj, confirming lipoperoxidation as a key factor in the final common pathway of secondary posttraumatic brain damage.

Effects of high-dose IgG on survival of surgical patients with sepsis scores of 20 or greater.

Sixty-two consecutive septic surgical patients receiving standard multimodal intensive care unit treatment who developed a sepsis score of 20 or greater (day 0) were randomized to receive 0.4 g/kg of either intravenous IgG (29 patients) or human albumin (controls; 33 patients), repeated on days +1 and +5, in a prospective, double-blind, multicenter study. The two groups were similar in age, initial sepsis scores, and acute physiology and chronic health evaluation II score. A significantly lower mortality was recorded in the IgG-treated group (38%) than in controls (67%). Septic shock was the cause of death in 7% of IgG-treated patients and in 33% of controls. The results of this study indicate that high-dose IgG improves survival and decreases death from septic shock in surgical patients with a sepsis score of 20 or greater.

Surveillance of infections acquired in intensive care: usefulness in clinical practice.

Nosocomial infection surveillance is common in the USA and in some European countries but in Italy few hospitals use it. In order to evaluate its usefulness in clinical practice we performed a one year prospective epidemiological study that included 178 patients, admitted to an intensive care unit (ICU) for more than 48 h. Median ICU stay was 16 days. Trauma and neurological diseases accounted for 65% of admissions. The selected population had high severity scores and required a large number of invasive procedures for diagnosis and therapy. The most common infections were: pneumonia 46/1000 ventilator-days; urinary tract infections 17/1000 catheter-days; central venous catheter infections 14.5/1000 catheter-days with 1.7/1000 CVC-related sepsis; bacteraemic sepsis 12/1000 ICU-days. The most frequent pathogens were Staphylococcus aureus,Pseudomonas aeruginosa, other Gram-negative aerobes and Candida spp. Antimicrobial resistance was substantial, with 68% methicillin-resistance in S. aureus and 76% of P. aeruginosa displaying antibiotic resistance. Severe sepsis or septic shock occurred in 30 patients (8/1000 ICU-days), and three patients died from septic shock of unknown origin (10% case fatality rate). There were no case fatalities for pneumonia and bacteraemic sepsis. Overall, ICU-acquired infections were not associated with an increased risk of death.

Epidemiology of nosocomial infection in 125 Italian intensive care units.

AIM: A continuous infection surveillance program was conducted by GiViTI throughout 2006 in Intensive Care Units (ICUs). METHODS: This was a prospective epidemiological study carried out in 125 Italian intensive care units. All patients have been included in the study. Aside from the detailed clinical information collected for all patients, in cases of infection upon ICU admission and for the first site-specific episode that occurred during the patient's stay, the following data were collected: severity upon admission, micro-organisms and their antibiotic resistance patterns, subsequent multiple episodes in the same site, origin of infections and maximum severity reached. The diagnostic criteria for all infections are explicitly stated. RESULTS: A total of 34,472 patients entered the study. Infection upon admission was present in 12.6% of patients, with a high level of ICU and hospital mortality (29.4% and 38.7%, respectively). In 3148 patients one or more infections were reported as ICU-acquired with an overall incidence of 9.1% and an ICU and hospital mortality of 27.2% and 35.1%, respectively. Out of the device-related infections, ventilator-associated pneumonia was the most frequently diagnosed (8.9/1000 days on ventilator). Catheter-related blood stream infection was reported with a low incidence (1.9/1000 central venous catheter days). Nearly 20% of more than 5000 isolated microorganisms were classified as multi-drug resistant, with methicillin-resistant Staphylococcus aureus as the most frequently reported bug. CONCLUSIONS: The ad hoc expanded GiViTI software "Margherita2" allows continuous infection surveillance in Italian ICUs, annually providing an extensive and updated database. Interventions to improve infection prevention and patient safety should be tailored to accommodate these data.