Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Subclinical cardiac dysfunction may impact on fluid and vasopressor administration during early resuscitation of septic shock.

BACKGROUND: According to the Surviving Sepsis Campaign (SSC) fluids and vasopressors are the mainstays of early resuscitation of septic shock while inotropes are indicated in case of tissue hypoperfusion refractory to fluids and vasopressors, suggesting severe cardiac dysfunction. However, septic cardiac disfunction encompasses a large spectrum of severities and may remain "subclinical" during early resuscitation. We hypothesized that "subclinical" cardiac dysfunction may nevertheless influence fluid and vasopressor administration during early resuscitation. We retrospectively reviewed prospectically collected data on fluids and vasoconstrictors administered outside the ICU in patients with septic shock resuscitated according to the SSC guidelines that had reached hemodynamic stability without the use of inotropes. All the patients were submitted to transpulmonary thermodilution (TPTD) hemodynamic monitoring at ICU entry. Subclinical cardiac dysfunction was defined as a TPTD-derived cardiac function index (CFI) ≤ 4.5 min-1. RESULTS: At ICU admission, subclinical cardiac dysfunction was present in 17/40 patients (42%; CFI 3.6 ± 0.7 min-1 vs 6.6 ± 1.9 min-1; p < 0.01). Compared with patients with normal CFI, these patients had been resuscitate with more fluids (crystalloids 57 ± 10 vs 47 ± 9 ml/kg PBW; p < 0.01) and vasopressors (norepinephrine 0.65 ± 0.25 vs 0.43 ± 0.29 mcg/kg/min; p < 0.05). At ICU admission these patients had lower cardiac index (2.2 ± 0.6 vs 3.6 ± 0.9 L/min/m2, p < 0.01) and higher systemic vascular resistances (2721 ± 860 vs 1532 ± 480 dyn*s*cm-5/m2, p < 0.01). CONCLUSIONS: In patients with septic shock resuscitated according to the SSC, we found that subclinical cardiac dysfunction may influence the approach to fluids and vasopressor administration during early resuscitation. Our data support the implementation of early, bedside assessment of cardiac function during early resuscitation of septic shock.

Cefiderocol-Based Combination Therapy for "Difficult-to-Treat" Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives.

Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as "rescue" treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunocompromised subjects due to solid organ transplantation (2/4) or hematological malignancy (2/4). Overall, 10/13 infections were caused by carbapenem-resistant Acinetobacter baumannii, one by KPC-positive ceftazidime/avibactam-resistant Klebsiella pneumonia and two by Pseudomonas aeruginosa XDR. Based on clinical, microbiological and hematobiochemical evaluation, cefiderocol was associated with different companion drugs, particularly with fosfomycin, high-dose tigecycline and/or colistin. Microbiological eradication was achieved in all cases and the 30-day survival rate was 10/13; two patients died due to SARS-CoV-2 lung failure, whereas one death was attributed to subsequent infections. No recurrent infections within 30 days were reported. Finally, we hereby discuss the therapeutic potential of cefiderocol and the possible place in the therapy of this novel drug.

Triple Intrathecal Combination Therapy for End-Stage Cancer-Related Refractory Pain: A Prospective Observational Study with Two-Month Follow-Up.

INTRODUCTION: In cancer-related pain refractory to systemic opioids, intrathecal (IT) administration of morphine can be a useful strategy. In clinical practice, IT morphine is usually combined with other drugs with different mechanisms of action, in order to obtain a synergistic analgesic effect. However, the discussion on efficacy and safety of IT combination therapy is still ongoing. The aim of this observational study was to report the effects of an IT combination of low doses of ziconotide, morphine, and levobupivacaine in end-stage cancer refractory pain. METHODS: Sixty adult patients, 21 females and 39 males, were enrolled to an IT device implant. The mean visual analogue scale of pain intensity (VASPI) score was 88 ± 20 mm. All patients started with a triple combination therapy: the initial IT dose of morphine was calculated for each patient based on the equivalent daily dose of morphine; an oral/IT ratio of 400/1 was used. For ziconotide, a standard slow titration schedule was started at 1.2 µg/day and the initial dose of levobupivacaine was 3 mg/day. RESULTS: The initial IT mean doses of morphine, ziconotide, and levobupivacaine were 0.8 ± 0.3 mg/day, 1.2 mcg/day and 3 mg/day, respectively. At day 2, a significant reduction in VASPI score was registered (49 ± 17, p < 0.001), and this significant reduction persisted at 56 days (mean VASPI score 44 ± 9, p < 0.001), with mean doses of morphine 2 ± 1 mg/day, ziconotide 2.8 ± 1 mcg/day, and levobupivacaine 3.8 ± 2 mg/day. Very few adverse effects (AEs) were observed. Patients' satisfaction was very high during the entire study period. CONCLUSIONS: Our results, within the limit of the study design, suggest that the IT combination of ziconotide, morphine, and levobupivacaine, at low doses, allows safe and rapid control of refractory cancer pain, with high levels of patient satisfaction.

Hemodynamic goal-directed therapy and postoperative kidney injury: an updated meta-analysis with trial sequential analysis.

BACKGROUND: Perioperative goal-directed therapy (GDT) reduces the risk of renal injury. However, several questions remain unanswered, such as target, kind of patients and surgery, and role of fluids and inotropes. We therefore update a previous analysis, including all studies published in the meanwhile, to clarify the clinical impact of this strategy on acute kidney injury. MAIN BODY: Randomized controlled trials enrolling adult patients undergoing major surgery were considered. GDT was defined as perioperative monitoring and manipulation of hemodynamic parameters to reach normal or supranormal values by fluids alone or with inotropes. Trials comparing the effects of GDT and standard hemodynamic therapy were considered. Primary outcome was acute kidney injury, whichever definition was used. Meta-analytic techniques (analysis software RevMan, version 5.3) were used to combine studies, using random-effect odds ratios (OR) and 95% confidence intervals (CI). Trial sequential analyses were performed including all trials and considering only low risk of bias trials. Sixty-five trials with an overall sample of 9308 patients were included. OR for the development of renal injury was 0.64 (95% CI, 0.62-0.87; p = 0.0003), with no statistical heterogeneity. Trial sequential analyses and sensitivity analysis including studies with low risk of bias confirmed the main results. A significant decrease in renal injury rate was observed in studies that adopted cardiac output and oxygen delivery as hemodynamic target and that used both fluids and inotropes. The postoperative kidney injury rate was significantly lower in trials enrolling "high-risk" patients and major abdominal and orthopedic surgery. SHORT CONCLUSION: The present meta-analysis suggests that targeting GDT to perioperative systemic oxygen delivery, by means of fluids and inotropes, can be the best way to improve renal perfusion and oxygenation in high-risk patients undergoing major abdominal and orthopedic surgery.

Perioperative hemodynamic goal-directed therapy and mortality: a systematic review and meta-analysis with meta-regression.

INTRODUCTION: Recent data found that perioperative goal directed therapy (GDT) was effective only in higher control mortality rates (>20%) with a relatively high heterogeneity that limited the strength of evidence. The aim of the present meta-analysis was to clearly understand which high risk patients may benefit of GDT. EVIDENCE ACQUISITION: Systematic review of randomized controlled trials with meta-analyses, including a meta-regression technique. MEDLINE, EMBASE, and The Cochrane Library databases were searched (1980-January 2015). Trials enrolling adult surgical patients and comparing the effects of GDT versus standard hemodynamic therapy were considered. The primary outcome measure was mortality. Data synthesis was obtained by using Odds Ratio (OR) with 95% confidence interval (CI) by random-effects model. EVIDENCE SYNTHESIS: Fifty eight studies met the inclusion criteria (8171 participants). Pooled OR for mortality was 0.70 (95% CI 0.56-0.88, P=0.002, no statistical heterogeneity). GDT significantly reduced mortality when it is >10% in control group (OR 0.43, 95% CI 0.30-0.61, P<0.00001). The meta-regression model showed that the cut off of 10% of mortality rate in control group significantly differentiates 43 studies from the other 15, with a regression coefficient b of -0.033 and a P value of 0.0001. The significant effect of GDT was driven by high risk of bias studies (OR 0.48, 95% CI 0.34-0.67, P<0.0001). CONCLUSIONS: The present meta-analysis, adopting the meta-regression technique, suggests that GDT significantly reduces mortality even when the event control rate is >10%.

Fusariosis in a Patient with Acute Myeloid Leukemia: A Case Report and Review of the Literature.

Fusarium spp. causes infections mostly in patients with prolonged neutropenia. We describe the case of a disseminated Fusarium solani infection in a patient with acute myeloid leukemia which never reached complete remission during its clinical course. The patient had profound neutropenia and developed skin nodules and pneumonia in spite of posaconazole prophylaxis. F. solani was isolated from blood and skin biopsy, being identified from its morphology and by molecular methods. By broth dilution method, the strain was resistant to azoles, including voriconazole and posaconazole, and to echinocandins. MIC to amphotericin B was 4 mg/L. The patient initially seemed to benefit from therapy with voriconazole and amphotericin B, but, neutropenia perduring, his clinical condition deteriorated with fatal outcome. All efforts should be made to determine the correct diagnosis as soon as possible in a neutropenic patient and to treat this infection in a timely way, assuming pathogen susceptibility while tests of antimicrobial susceptibility are pending. A review of the most recent literature on invasive fungal infections is reported.

Good medical practices in the use of antibiotic prophylaxis in a surgery ward: Results of a 2013 Apulian study.

This study describes the changes in the performance of health care workers regarding the control of health care-associated infection in a surgical ward of University Hospital Policlinico, Bari, Italy, before and after a training program and adoption of bundles on antibiotic therapy. There were 194 patients recruited (pre: n = 98; post: n = 96), of which 149 (76.8%) had undergone surgery. We documented a change in the proportions of patients who received in-ward prophylactic antibiotics (from 46/98 to 22/96, P < .05), surgical patients undergoing antibiotic prophylaxis in the operating room (from 18/64 to 36/85, P < .05), and average duration of prophylaxis (from 5.9 ± 4.9 to 2.9 ± 2.7 days, P < .0001). Results confirmed correspondence between the intervention and results recorded.

Cost of care and antibiotic prescribing attitudes for community-acquired complicated intra-abdominal infections in Italy: a retrospective study.

INTRODUCTION: Complicated intra-abdominal infections (cIAIs) are a common cause of morbidity worldwide, and in spite of improvements in patient care, therapeutic failure still occurs, impacting in-hospital resource consumption. This study aimed to assess the costs associated with the treatment of community-acquired cIAIs, from the Italian National Health Service perspective. METHODS: This retrospective study analyzed the charts of patients who were discharged from four Italian university hospitals between January 1 and December 31, 2009 with a primary diagnosis of community-acquired cIAIs. Patient characteristics, diagnosis, surgical procedure, antibiotic therapy, and length of hospital stay were all recorded and the cost of total hospital care was estimated. Costs were calculated in Euros at 2009 values. RESULTS: The records of 260 patients (mean age 48.9 years; 57% males) were analyzed. The average cost of care for a patient hospitalized due to cIAI was €4385 (95% CI 3650-5120), with an average daily cost of €419 (95% CI 378-440). Antibiotic therapy represented just under half (44.3%) of hospitalization costs. The strongest predictor of the increase in hospital costs was clinical failure: patients who clinically failed received an average of 8.2 additional days of antibiotic therapy and spent 11 more days in hospital compared with patients who responded to first-line therapy (both p < 0.05 vs. patients who were successfully treated). Furthermore, they incurred €5592 in additional hospitalization costs (2.88 times the cost associated with clinical success) with 53% (€2973) of the additional costs attributable to antibiotic therapy. Overall, antibiotic appropriateness rate was 78.8% (n = 205), and was significantly higher in patients receiving combination therapy compared with those treated with monotherapy (97.3% vs. 64.6%). CONCLUSION: The results of this study suggest that hospitals need to be aware of the clinical and economic consequences of antibiotic therapy of cIAIs and to reduce overall resource use and costs by improving the rate of success with appropriate initial empiric therapy.

Intra-abdominal hypertension in cardiac surgery.

OBJECTIVES: The occurrence of intra-abdominal hypertension (IAH), as well as its promoting factors in cardiac surgery, has been poorly explored. The aim of the present study was to characterize intra-abdominal pressure (IAP) variations in patients undergoing cardiac surgical procedures, and to identify the risk factors for IAH in this setting. METHODS: All consecutive adult patients requiring postoperative intensive care unit admission for >24 h were enrolled. Demographic data, pre-existing comorbidities, type and duration of surgery, cardiopulmonary bypass (CPB) use and duration, perioperative IAP, organ function and fluid balance were recorded. IAH was defined as a sustained increase in IAP >12 mmHg. Multivariate logistic regression and stepwise analyses identified the baseline and perioperative variables associated with IAH. RESULTS: Of 69 patients, 22 (31.8%) developed IAH. In the logistic model, baseline IAP, high central venous pressure, vasoactive drugs administration, positive fluid balance, AKI, CPB, total sequential organ failure assessment score and age were all promoting factors for IAH (Hosmer-Lemeshow χ(2) = 7.23; P = 0.843). Baseline IAP, high central venous pressure and positive fluid balance were independent risk factors for IAH in the stepwise analysis. The ROC curve analysis, obtained by plotting the occurrence of IAH vs the IAP baseline value, showed an AUC of 0.75 (SE 0.064; 99% CI 0.62-0.87; P < 0.0001). The best IAP cut-off value was at 8 mmHg (sensitivity 63% and specificity 76%). Considering on- and off-pump surgery groups, fluid balance and vasoactive drugs use were significantly higher in the on-pump group. Linear regression analysis showed a positive correlation (P = 0.0001) between IAP changes and fluid balance only in the on-pump group. CONCLUSIONS: IAH develops in one-third of cardiac surgery patients and is strongly associated with higher baseline IAP values, higher central venous pressure, positive fluid balance, extracorporeal circulation, use of vasoactive drugs and AKI. Determinants of IAH should be accurately assessed before and after surgery, and patients presenting risk factors must be monitored properly during the perioperative period. In this context, the baseline value of IAP may be a valuable and early warning parameter for IAH occurrence.

Haemodynamic goal-directed therapy in cardiac and vascular surgery. A systematic review and meta-analysis.

In cardiovascular surgery, reduced organ perfusion and oxygen delivery contribute to increased postoperative morbidity and prolonged intensive care unit stay. Goal-directed therapy (GDT), a perioperative haemodynamic strategy aiming to increase cardiac output, is helpful in preventing postoperative complications, but studies in the context of cardiovascular surgery have produced conflicting results. The purpose of the present meta-analysis is to determine the effects of perioperative haemodynamic goal-directed therapy on mortality and morbidity in cardiac and vascular surgery. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched until July 2011. Randomized controlled trials reporting on adult cardiac or vascular surgical patients managed with perioperative GDT or according to routine haemodynamic practice were included. Primary outcome measures were mortality and morbidity. Data synthesis was obtained by using odds ratio (OR) with 95% confidence interval (CI) by a random effects model. An OR <1 favoured GDT. Statistical heterogeneity was assessed by Q and I(2) statistics. Eleven articles (five cardiac surgery and six vascular procedures), enrolling a total sample of 1179 patients, were included in the analysis. As compared with routine haemodynamic practice, perioperative GDT did not reduce mortality in either cardiac or vascular surgery (pooled OR 0.87; 95% CI 0.37-2.02; statistical power 64%). GDT significantly reduced the number of cardiac patients with complications (OR 0.34; 95% CI 0.18-0.63; P = 0.0006), but no effect was observed in vascular patients (OR, 0.84; 95% CI 0.45-1.56; P = 0.58). Perioperative GDT prevents postoperative complications in cardiac surgery patients, while it has no effect in vascular surgery. The different characteristics and comorbidities of the population enrolled could explain these conflicting results. More trials conforming to the characteristics of low-risk-of-bias studies and enrolling a larger and well-defined population of patients are needed to better clarify the effect of GDT in the specific setting of cardiovascular surgery.

Haemodynamic goal-directed therapy and postoperative infections: earlier is better. A systematic review and meta-analysis.

INTRODUCTION: Infectious complications are the main causes of postoperative morbidity. The early timing of their promoting factors is the rationale for perioperative strategies attempting to reduce them. Our aim was to determine the effects of perioperative haemodynamic goal-directed therapy on postoperative infection rates. METHODS: We performed a systematic review and meta-analysis. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched up to March 2011. Randomised, controlled trials of major surgery in adult patients managed with perioperative goal-directed therapy or according to routine haemodynamic practice were included. Primary outcome measure was specific type of infection. RESULTS: Twenty-six randomised, controlled trials with a combined total of 4,188 participants met our inclusion criteria. Perioperative goal-directed therapy significantly reduced surgical site infections (pooled OR 0.58, 95% CI 0.46 to 0.74; P < 0.0001), pneumonia (pooled OR 0.71, 95% CI 0.55 to 0.92; P = 0.009), and urinary tract infections (pooled OR 0.44, 95% CI 0.22 to 0.84; P = 0.02). A significant benefit was found regarding total infectious episodes (OR 0.40, 95% CI 0.28 to 0.58; P < 0.00001). CONCLUSIONS: Flow-directed haemodynamic therapy designed to optimise oxygen delivery protects surgical patients against postoperative hospital-acquired infections and must be strongly encouraged, particularly in the high-risk surgical population.

Jaundice in critical illness: promoting factors of a concealed reality.

OBJECTIVE: In critical illness, liver dysfunction (LD) is associated with a poor outcome independently of other organ dysfunctions. Since strategies to support liver function are not available, a timely and accurate identification of factors promoting LD may lead to prevention or attenuation of its consequences. The aim of this study was to assess risk factors for LD in critically ill patients. DESIGN: Prospective, observational study. SETTING: A multidisciplinary intensive care unit (ICU) of a university hospital. PATIENTS: All patients consecutively admitted over a 6-month period. INTERVENTION: None. MEASUREMENTS AND RESULTS: LD was defined as serum bilirubin levels >or=2 mg/dl and lasting for at least 48 h. Out of 283 patients, 141 matched inclusion criteria. Forty-four patients (31.2%) showed LD (LD group), while 97 (68.8%) were included in control group (C group). A binomial analysis showed that LD occurrence was associated with moderate (odds ratio [OR] 3.11; p=0.04) and severe shock (OR 3.46; p= 0.05), sepsis (OR 3.03; p=0.04), PEEP ventilation (OR 4.25; p=0.006), major surgery (OR 4.03; p=0.03), and gram-negative infections (OR 3.94; p=0.002). In stepwise multivariate analysis, the single independent predictive factors of LD resulted in severe shock (p=0.002), sepsis (p=0.03), PEEP ventilation (p=0.04), and major surgery (p=0.05). CONCLUSIONS: In critically ill patients jaundice is common, and severe shock states, sepsis, mechanical ventilation with PEEP and major surgery are critical risk factors for its onset. Since there is no specific treatment, prompt resuscitation, treatment of sepsis and meticulous supportive care will likely reduce its incidence and severity.