Outpatient parenteral antimicrobial therapy (OPAT) from an emergency model applied during the COVID-19 pandemic to standard of care: Preliminary lessons from our experience.

OBJECTIVES: We wish to report on our experience of OPAT during the first two years of the COVID19 outbreak. PATIENTS AND METHODS: We recorded data on all patients treated in the OPAT regimen in 2020 and 2021 and compared overall trends, use of carbapenems and saved days of hospitalization. RESULTS: The OPAT model enabled us to ensure the administration of first choice antibiotic therapy to 239 patients with an increase of 21.3% from 2020 to 2021 (108 vs 131). Applying this model, we also recorded a reduction in the use of carbapenems from 33% in 2020 to 26% in 2021 and a total of 3041 recovery days saved in 2021.The clinical cure rate reached 94%. Few adverse events occurred (35/239; 14.6%), and they did not require hospitalization. CONCLUSION: OPAT is a safe, efficacious, and cost-effective model that functioned effectively during the COVID-19 crisis and could become the standard of care for the treatment of selected patients.

Catheter salvage strategies in children with central venous catheter-related or -associated bloodstream infections: a systematic review and meta-analysis.

BACKGROUND: Optimal management of central venous catheter-related, or -associated, bloodstream infections (CRBSI or CLABSI) in children is not established. AIM: To evaluate success of catheter salvage strategies in paediatric patients. METHODS: Studies were retrieved from medical databases and article reference lists. Data were collected relating to clinical outcomes of two treatments: systemic antibiotics alone or in association with antimicrobial lock therapy (ALT). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from a mixed logistic effects model. Heterogeneity was summarized using I2 statistics. Publication bias was investigated by Egger's regression test and funnel plots. FINDINGS: From 345 identified publications, 19 met inclusion criteria (total of 914 attempted salvage strategies). To achieve successful catheter salvage, in CRBSI the addition of ALT was superior to systemic antibiotics alone (OR: -0.40; 95% CI: -1.41, 0.62): 77% (95% CI: 69, 85; I2 = 42.5%; P = 0.12) and 68% of success (95% CI: 59, 77; I2 = 0; P < 0.05), respectively. CRBSI recurrence was less common in studies that used ALT compared with systemic antibiotics alone: 5% (95% CI: 0, 13; I2 = 59.7%; P = 0.03) and 18% of recurrence (95% CI: 9, 28; I2 = 0; P < 0.05), respectively. Recurrences were low with both antibiotic locks and ethanol lock. No clear benefits of ALT addition compared to systemic antibiotic only were found in CLABSI (OR: -0.81; 95% CI: -0.80, 2.43). CONCLUSION: The addition of an antimicrobial lock solution to systemic antibiotic may be beneficial for successful catheter salvage in paediatric patients with CRBSI, depending on aetiology, whereas no statistically significant difference between systemic antibiotic with or without addition of an antimicrobial lock solution was found regarding CLABSI.

Procalcitonin is useful in driving the choice of early antibiotic treatment in patients with bloodstream infections.

OBJECTIVE: To evaluate whether PCT levels could be used to distinguish among different bacterial and fungal etiologies in patients with documented bloodstream infection (BSI). PATIENTS AND METHODS: Monocentric retrospective cohort study on patients admitted to the Fondazione Policlinico Gemelli Hospital between December 2012 and November 2015 with BSI. Those who had undergone PCT determination within 48 hours of when the first positive blood culture was sampled were included in the study. RESULTS: Four hundred and one patients were included in the study. Both the 24h and 48h PCT values were significantly higher in patients with Gram-negative (GN) BSI than in those with Gram-positive (GP) or candida BSI (p at ANOVA = 0.003). A PCT value of > 1 ng/ml was found in 31.5% of patients with GN BSI. Less than 7% of people with candida BSI had PCT level of > 1 ng/ml. At multivariable regression analysis, GN BSI, septic shock, and plasma creatinine were significantly correlated with PCT values. CONCLUSIONS: PCT may be of value in distinguishing GN BSI from GP, and fungal BSI and PCT values of > 1 ng/ml could be used to prevent unnecessary antifungal treatment.

A 72-h intervention for improvement of the rate of optimal antibiotic therapy in patients with bloodstream infections.

Antimicrobial stewardship programs are implemented to optimize the use of antibiotics and control the spread of antibiotic resistance. Many antimicrobial stewardship interventions have demonstrated significant efficacy in reducing unnecessary prescriptions of antibiotics, the duration of antimicrobial therapy, and mortality. We evaluated the benefits of a combination of rapid diagnostic tests and an active re-evaluation of antibiotic therapy 72 h after the onset of bloodstream infection (BSI). All patients with BSI from November 2015 to November 2016 in a 1100-bed university hospital in Rome, where an Infectious Disease Consultancy Unit (Unità di Consulenza Infettivologica, UDCI) is available, were re-evaluated at the bedside 72 h after starting antimicrobial therapy and compared to two pre-intervention periods: the UDCI was called by the ward physician for patients with BSI and the UDCI was called directly by the microbiologist immediately after a pathogen was isolated from blood cultures. Recommendations for antibiotic de-escalation or discontinuation significantly increased (54%) from the two pre-intervention periods (32% and 27.2%, p < 0.0001). Appropriate escalation also significantly increased (22.5%) from the pre-intervention periods (8.1% and 8.2%, p < 0.0001). The total duration of antibiotic therapy decreased with intervention (from 21.9 days [standard deviation, SD 15.4] in period 1 to 19.3 days [SD 13.3] in period 2 to 17.7 days in period 3 [SD 11.5]; p = 0.002) and the length of stay was significantly shorter (from 29.7 days [SD 29.3] in period 1 to 26.8 days [SD 24.7] in period 2 to 24.2 days in period 3 [SD 20.7]; p = 0.04) than in the two pre-intervention periods. Mortality was similar among the study periods (31 patients died in period 1 (15.7%), 39 (16.7%) in period 2, and 48 (15.3%) in period 3; p = 0.90). Rapid diagnostic tests and 72 h re-evaluation of empirical therapy for BSI significantly correlated with an improved rate of optimal antibiotic therapy and decreased duration of antibiotic therapy and length of stay.

Intraventricular versus intravenous colistin for the treatment of extensively drug resistant Acinetobacter baumannii meningitis.

BACKGROUND AND PURPOSE: Reports on the safety and efficacy of intraventricularly administered (IVT) colistin for the treatment of Acinetobacter baumannii ventriculomeningitis in adults are limited and no comparative studies of IVT colistin versus intravenous (IV) therapy alone have been published. This study compared outcomes of patients with postneurosurgical ventriculomeningitis caused by extensively drug-resistant A. baumannii treated with IV colistin or IV plus IVT colistin. METHODS: In an 11-year period, information on 18 consecutive patients with extensively drug-resistant A. baumannii ventriculomeningitis was collected. Infection was defined on the basis of (i) isolation of A. baumannii from the cerebrospinal fluid (CSF); (ii) laboratory evidence of CSF infection; (iii) signs/symptoms of central nervous system (CNS) infection. Patients were divided into group 1 (nine patients, IV colistin alone) and group 2 (nine patients, IV plus IVT colistin). RESULTS: Cerebrospinal fluid sterilization was documented for 12 of 18 patients (66.6%). The CSF sterilization rate was 33.3% in group 1 and 100% in group 2 (P = 0.009). The mean time to CSF sterilization was 21 days (range 8-48). Five patients died due to A. baumannii CNS infection (all in group 1), and five deaths were unrelated to A. baumannii ventriculomeningitis. Intensive care unit mean length of stay was shorter in group 2 (20.7 vs. 41.6 days, P = 0.046). Crude relative risk ratio of cumulative incidence of persistent CNS infection in group 1 versus group 2 was 13. No cases of chemical meningitis due to intrathecal colistin administration were encountered. CONCLUSIONS: Intraventricular colistin administration is much more effective than IV therapy alone and does not seem to add further toxicity.

Initial antifungal strategy does not correlate with mortality in patients with candidemia.

The incidence of Candida bloodstream infections (BSIs) has increased over time, especially in medical wards. The objective of this study was to evaluate the impact of different antifungal treatment strategies on 30-day mortality in patients with Candida BSI not admitted to intensive care units (ICUs) at disease onset. This prospective, monocentric, cohort study was conducted at an 1100-bed university hospital in Rome, Italy, where an infectious disease consultation team was implemented. All cases of Candida BSIs observed in adult patients from November 2012 to April 2014 were included. Patients were grouped according to the initial antifungal strategy: fluconazole, echinocandin, or liposomal amphotericin B. Cox regression analysis was used to identify risk factors significantly associated with 15-day and 30-day mortality. During the study period, 130 patients with candidemia were observed (58 % with C. albicans, 7 % with C. glabrata, and 23 % with C. parapsilosis). The first antifungal drug was fluconazole for 40 % of patients, echinocandin for 57.0 %, and liposomal amphotericin B for 4 %. During follow-up, 33 % of patients died. The cumulative mortality 30 days after the candidemia episode was 30.8 % and was similar among groups. In the Cox regression analysis, clinical presentation was the only independent factor associated with 15-day mortality, and Acute Physiology and Chronic Health Evaluation (APACHE) II score and clinical presentation were the independent factors associated with 30-day mortality. No differences in 15-day and 30-day mortality were observed between patients with and without C. albicans candidemia. In patients with candidemia admitted to medical or surgical wards, clinical severity but not the initial antifungal strategy were significantly correlated with mortality.

Successful treatment of multidrug-resistant Acinetobacter baumannii ventriculitis with intrathecal and intravenous colistin.

Acinetobacter baumannii (AB) nosocomial infections, especially those due to multi-drug resistant (MDR) strains, are increasingly detected. We report a case of a 42-year-old male patient affected by low-grade ependymoma who developed AB-MDR post-neurosurgical ventriculitis. Initially, because of in vitro susceptibility, we used a combination of intravenous colistin and tigecycline. This treatment resulted in the improvement of the patient's initial condition. However, soon after, the infection relapsed; tigecycline was stopped and treatment with intrathecal colistin was initiated. Cure was achieved by continuing this treatment for approximately three weeks, without adverse effects.

Hospital-acquired candidemia in HIV-infected patients. Incidence, risk factors and predictors of outcome.

A retrospective case-control study was performed to analyze hospital-acquired candidemia in HIV-positive patients. To understand the impact of Highly Active Antiretroviral Therapy (HAART) on the incidence of nosocomial candidemia, two time periods were compared: A (1992-1996) and B (1997-2001). 32 out of 38 (84%) cases of candidemia were hospital-related. A significant reduction in the incidence of all cases of hospital-acquired candidemia has been observed in the post-HAART in respect to pre-HAART period (0.09 episodes vs. 1.1 per 100/py). Multivariate analysis showed that the presence of central venous catheter was the only variable independently associated with the development of nosocomial candidemia. The overall mortality rate was 59%. Univariate analysis indicated three prognostic indicators: presence of concomitant opportunistic infections, isolation of non-albicans Candida species; neutropenia. Multivariate analysis of prognostic indicators showed that isolation of non-albicans Candida species is the only independent variable. Despite the use of HAART, this disease still represents a severe complication of advanced stage of AIDS.

Impact of highly active antiretroviral therapy (HAART) on the incidence of bacterial infections in HIV-infected subjects.

The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) on the incidence of bacterial infections in HIV-infected patients. Two time periods were compared: (A) January 1992-December 1995 (before HAART) and (B) January 1997-December 2000 (after HAART). During the study periods, we observed 931 patients with bacterial infections, i.e. 322 with bacteremia, 369 with bacterial pneumonia and 240 with urinary tract infections, out of 4,242 HIV-infected subjects admitted to the Department of Infectious Diseases of a large university hospital. By comparing the overall incidence of bacterial infections during periods A and B, a statistically significant difference, from 32% to 18% (p<0.01), was observed. Analysis of risk factors of community- and hospital-acquired bacterial infections did not significantly differ in the two study periods. This study establishes that a significant reduction in bacterial infection incidence occurred in HIV-infected subjects when HAART became the standard therapy for HIV infection.

Correlation between cidofovir-associated uveitis and failing immunorestoration during HAART.

In order to elucidate the factors related to the development of cidofovir-associated uveitis in AIDS patients receiving highly active antiretroviral therapy, the characteristics of 17 AIDS patients with Cytomegalovirus retinitis ( n=10) or progressive multifocal leukoencephalopathy ( n=7) treated with intravenous cidofovir were evaluated. Six cases of cidofovir-associated uveitis occurred among the patients with retinitis. No cases were detected among the patients with progressive multifocal leukoencephalopathy. Stepwise linear regression analysis revealed a significantly higher HIV-viremia level ( P=0.01) and a significantly lower CD4+ cell count ( P=0.009) among cases at the time of uveitis onset in comparison with patients who did not develop uveitis. Thus, cidofovir-associated uveitis seems to occur more frequently in AIDS patients with retinitis in whom highly active antiretroviral therapy fails to restore immunity.

Changing disease patterns in focal brain lesion-causing disorders in AIDS.

OBJECTIVES: To assess temporal trends of the different disorders causing focal brain lesions (FBL) in HIV-infected patients and to examine the reliability of the U.S. Centers for Disease Control and Prevention (CDC) criteria for presumptive diagnosis of toxoplasmic encephalitis (TE) for the years 1991 to 1996. DESIGN/METHODS: A prospective, monocenter study. Percentages of occurrence of the different FBL-causing disorders for each year were calculated. Temporal trends were analyzed by chi2 test for linear trend and multivariate polytomous nonordinal logistic regression. The positive predictive value (PPV) of the CDC's presumptive criteria for the diagnosis of TE (recent onset of a focal neurologic abnormality consistent in intracranial disease or a reduced level of consciousness, evidence on brain imaging of a lesion having mass effect or the radiographic appearance of which is enhanced by injection of contrast medium, and serum antibody to toxoplasmosis) was calculated using contingency tables for each calendar year. RESULTS: A highly significant decline of the risk of TE and an increase of the probability of patients to take anti-Toxoplasma prophylaxis were observed. A threefold but statistically not significant augmented risk of diagnosing both primary central nervous system lymphoma (PCNSL) and progressive multifocal leucoencephalopathy (PML) has been registered for 1996 compared with 1991. Among FBL showing contrast enhancement, the increased finding of PCNSL over the years studied was significant. The probability of other FBL-causing disorders, such as focal viral encephalitis sustained by cytomegalovirus or herpes simplex virus, increased significantly over the years studied. Multivariate analysis confirmed that the year of diagnosis of FBL had a significant effect on the risk reduction of TE. The PPV of the CDC's criteria for the presumptive diagnosis of TE dropped from 100% for the year 1991 to 39% in the year 1996. A similar result was obtained in calculating the PPV of presumptive criteria only among patients without previous primary prophylaxis. CONCLUSIONS: Because of the significant decrease of TE and the increase of PCNSL empiric anti-Toxoplasma therapy no longer seems appropriate as a first-line approach to all HIV-positive patients with FBL. Especially in the case of a finding of FBL by contrast enhancement, new diagnostic strategies should be employed to identify the underlying disorder rapidly and accurately.

Diagnosis of AIDS-related focal brain lesions: a decision-making analysis based on clinical and neuroradiologic characteristics combined with polymerase chain reaction assays in CSF.

OBJECTIVE: To identify disease patterns in AIDS-related focal brain lesions (FBL) and to design a decision-making strategy for differential diagnosis. DESIGN: Prospective study. Probabilities of CNS disorders were calculated using Bayes' theorem according to clinical variables (mass effect at CT or MRI, Toxoplasma serology, anti-Toxoplasma prophylaxis) and to the results of polymerase chain reaction (PCR) assays. PATIENTS: 136 consecutive HIV-infected patients with a definitive diagnosis of FBL-causing disorder observed from 1991 to 1995 in a single clinical setting. INTERVENTIONS: Patients underwent empiric anti-Toxoplasma therapy. After 3 weeks, patients with progressive/stable disease underwent brain biopsy. In 66 patients Epstein-Barr virus (EBV)-DNA, JC virus (JCV)-DNA, and T gondii-DNA amplification was performed by PCR in CSF. Diagnostic criteria were histopathologic examination of bioptic or autoptic tissue specimens for all disorders and complete/partial resolution of FBL after empiric therapy for toxoplasmic encephalitis (TE). RESULTS: Neuroradiologic characteristics did not discriminate between TE and primary CNS lymphoma (PCNSL). Probability of TE was 0.87 in Toxoplasma-seropositive patients with mass effect who were not receiving anti-Toxoplasma prophylaxis, but only 0.59 if prophylaxis was performed. In seronegative patients with mass effect, the likelihood of PCNSL was 0.74. If EBV-DNA or T gondii-DNA tests were positive, the probability of PCNSL or TE increased to more than 0.96. The absence of T gondii-DNA did not exclude the possibility of a TE diagnosis. Among FBL without mass effect, the probability of progressive multifocal leukoencephalopathy (PML) was 0.81; this increased to 0.99 if JCV-DNA testing was positive. Sensitivity of brain biopsy was 93%, with a perioperative morbidity of 12% and a mortality of 2%. CONCLUSIONS: Due to the low diagnostic capability of clinical variables, PCR amplifications in CSF, especially for EBV-DNA and for JCV-DNA, represent, in most cases, an essential step in the differential diagnosis of AIDS-related FBL. This is particularly true in patients with FBL without mass effect or with mass effect and who are either seronegative or undergoing anti-Toxoplasma prophylaxis. Brain biopsy remains a necessary procedure in EBV-DNA-positive cases and in seronegative patients with FBL displaying a mass effect. Positive JCV-DNA testing may obviate the need for brain biopsy in patients with FBL without mass effect. An advanced diagnostic strategy based on combined clinical criteria and PCR tests may allow rapid and accurate identification of patients for prompt brain biopsy or specific therapy.

Disease-related factors associated with health-related quality of life in people with nonadvanced HIV disease assessed using an Italian version of the MOS-HIV Health Survey.

OBJECTIVE: This study was intended to present evidence for the reliability and validity of an Italian version of the MOS-HIV Health Survey and to identify important disease-related factors associated with health-related quality of life (HRQoL) in people with nonadvanced HIV. DESIGN: In this cross-sectional study, HRQoL was measured using an Italian version of the MOS-HIV Health Survey questionnaire in 213 HIV-infected people without previous opportunistic infections or neoplasms attending an outpatient clinic in a university hospital. Distribution of scores, reliability, and validity were calculated, and presence and frequency of HIV-related symptoms were recorded and transformed into a score. The relation of HRQoL values to sociodemographic, epidemiologic, and clinical data was assessed. RESULTS: The level of internal consistency of the Italian version of the MOS-HIV Health Survey was high (Cronbach's alpha, 0.80-0.93), and items demonstrated acceptable discrimination across scales. At linear regression analysis, all domains of HRQoL correlated with symptom score (r2 range, 0.07-0.41), but only the pain and physical-functioning scores showed a significant correlation with CD4 cell count. A weighted sum of single domains of HRQoL, TOTQoL, is also strongly correlated with symptom score (r2 = 0.57; p < .0001) but not with CD4 cell count (r2 = 0.01; p = .1). Using multivariate analysis, only symptom score (p < .0001) and total number of daily pills (p = .03) showed significant association with HRQoL. The same results were observed when analysis was performed only on people with CD4 levels <200/microl. CONCLUSIONS: This study presents the first evidence for the reliability and validity of a HRQoL instrument in Italian for people with HIV. Results also suggest a strong impact of symptoms on all measured dimensions of health status. The number of pills required to be taken daily is the only other significant factor associated with a lower HRQoL, whereas no relations were found with CD4 cell count or Karnofsky performance status values. To improve HRQoL in persons with nonadvanced HIV disease, symptom control could be a crucial element of medical treatment.

Aerosolized pentamidine, cotrimoxazole and dapsone-pyrimethamine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.

OBJECTIVE: To investigate the efficacy and safety of three regimens for primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) and to evaluate their effect on survival in patients with HIV infection. DESIGN: Randomized, open label, prospective trial. SETTING: A single Infectious Diseases Department in Italy. PATIENTS: HIV-infected patients (n = 197) with a CD4 count < 200 x 10(6)/l and without previous PCP or TE. INTERVENTIONS: Patients were randomly assigned to receive (1) aerosolized pentamidine (AP; 300 mg monthly), (2) cotrimoxazole (CTX; 160 mg trimethoprim and 800 mg sulfamethoxazole every other day), or (3) dapsone-pyrimethamine (DP; 100 mg weekly dapsone and 25 mg biweekly pyrimethamine). MAIN OUTCOME MEASURES: PCP, TE, death, and drug-limiting toxicity. Considering difference in PCP occurrence the trial was interrupted on June 1992. Observation was prolonged until June 1994 for TE and survival. RESULTS: Intention-to-treat analysis yielded PCP rates of 10.2 per 100 person-years in the AP, 2.0 in the CTX, and 32.1 in the DP group [adjusted relative risk of DP versus CTX: 17.5; 95% confidence interval (CI), 2.2-139.6; P = 0.007]. TE rates in patients with positive Toxoplasma serology were 25.6 per 100 person-years in the AP, 8.9 in the CTX and 9.4 in the DP group. In 'on treatment' analysis, no episode of TE developed in the DP group, and rates were 34.7 per 100 person-years in the AP and 2.5 in the CTX group (AP versus CTX: P = 0.01; AP versus DP: P = 0.004). The adjusted risk of mortality for the DP group was 2.8 times that of the CTX group in the first part of the study (95% CI, 1.1-7.3; P = 0.037), and 1.8 times (95% CI, 1.1-2.9; P = 0.02) in the prolonged follow-up. No significant difference in the occurrence of serious adverse reactions was observed between the three treatment groups. CONCLUSIONS: Intermittent CTX was more effective than low-dose DP and showed a slight but not significant advantage on AP for primary PCP prophylaxis. DP was associated with a shorter survival. Both CTX and DP resulted in a significant reduction in the risk of TE.