Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study.

BACKGROUND: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). METHODS: We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. RESULTS: Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality. CONCLUSIONS: In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

Severe and Rare Case of Human Dirofilaria repens Infection with Pleural and Subcutaneous Manifestations, Slovenia.

We report a case of human Dirofilaria repens infection in a woman in Slovenia who had concomitant pleural and subcutaneous manifestations of the infection. This case report illustrates the clinical course of a severe symptomatic parasitic infection that had multisystemic manifestations.

An international inventory of antimicrobial stewardship (AMS) training programmes for AMS teams.

BACKGROUND: Healthcare professionals are increasingly expected to lead antimicrobial stewardship (AMS) initiatives. This role in complex healthcare environments requires specialized training. OBJECTIVES: Little is known about the types of AMS training programmes available to clinicians seeking to play a lead role in AMS. We aimed to identify clinicians' awareness of AMS training programmes, characteristics of AMS training programmes available and potential barriers to participation. METHODS: AMS training programmes available were identified by members of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) via an online survey and through an online search in 2018. Individual training programme course coordinators were then contacted (September-October 2018) for data on the target audience(s), methods of delivery, intended outcomes and potential barriers to accessing the training programme. RESULTS: A total of 166/250 ESGAP members (66%) responded to the survey, nominating 48 unique AMS training programmes. An additional 32 training programmes were identified through an online search. AMS training programmes were from around the world. Less than half (44.4%) of respondents were aware of one or more AMS training programmes available, with pharmacists more aware compared with medical doctors and other professionals (73% versus 46% and 25%, respectively). AMS training programmes were most commonly delivered online (59%) and aimed at medical doctors (46%). Training costs and a lack of recognition by health professional societies were the most frequently cited barriers to participation in AMS training programmes. CONCLUSIONS: The development of a systematic inventory of AMS training programmes around the globe identifies opportunities and limitations to current training available. Improving access and increasing awareness amongst target participants will support improved education in AMS.

Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: a multicentre retrospective observational cohort study.

BACKGROUND: Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality. METHODS: This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009-15. We evaluated the association between ß-lactam plus aminoglycoside or quinolone combination therapy versus ß-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy. RESULTS: Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64-1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens. CONCLUSIONS: In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Ceftazidime, Carbapenems, or Piperacillin-tazobactam as Single Definitive Therapy for Pseudomonas aeruginosa Bloodstream Infection: A Multisite Retrospective Study.

BACKGROUND: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although ß-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. METHODS: A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with ß-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. RESULTS: Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52-2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67-2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). CONCLUSIONS: No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection.

Antibiotic use in patients with COVID-19: a 'snapshot' Infectious Diseases International Research Initiative (ID-IRI) survey.

BACKGROUND: Antibiotics may be indicated in patients with COVID-19 due to suspected or confirmed bacterial superinfection. OBJECTIVES: To investigate antibiotic prescribing practices in patients with COVID-19. METHODS: We performed an international web-based survey and investigated the pattern of antibiotic use as reported by physicians involved in treatment of COVID-19. SPSS Statistics version 25 was used for data analysis. RESULTS: The survey was completed by 166 participants from 23 countries and 82 different hospitals. Local guidelines for antibiotic use in COVID-19 patients were reported by 61.8% (n = 102) of participants and for 82.9% (n = 136) they did not differ from local community-acquired pneumonia guidelines. Clinical presentation was recognized as the most important reason for the start of antibiotics (mean score = 4.07 and SD = 1.095 on grading scale from 1 to 5). When antibiotics were started, most respondents rated as the highest the need for coverage of atypical pathogens (mean score = 2.8 and SD = 0.99), followed by Staphylococcus aureus (mean score = 2.67 and SD = 1.05 on bi-modal scale, with values 1 and 2 for disagreement and values 3 and 4 for agreement). In the patients on the ward, 29.1% of respondents chose not to prescribe any antibiotic. Combination of ß-lactams and macrolides or fluoroquinolones was reported by 52.4% (n = 87) of respondents. In patients in the ICU, piperacillin/tazobactam was the most commonly prescribed antibiotic. The mean reported duration of antibiotic treatment was 7.12 (SD = 2.44) days. CONCLUSIONS: The study revealed widespread broad-spectrum antibiotic use in patients with COVID-19. Implementation of antimicrobial stewardship principles is warranted to mitigate the negative consequences of antibiotic therapy.

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Ureaplasma parvum ventriculitis related to surgery and ventricular peritoneal drainage.

Ureaplasma spp. usually causes genitourinary infections; few reports in the literature describe extragenital infections, usually in immunocompromised patients. We present a case of Ureaplasma parvum ventriculitis in an immunocompetent patient related to ventriculoperitoneal drainage and surgery. Ureaplasma parvum was detected with broad range 16S rRNA PCR and cultured on A8 agar.

Young doctors' perspectives on antibiotic use and resistance: a multinational and inter-specialty cross-sectional European Society of Clinical Microbiology and Infectious Diseases (ESCMID) survey.

BACKGROUND: Postgraduate training has the potential to shape the prescribing practices of young doctors. OBJECTIVES: To investigate the practices, attitudes and beliefs on antibiotic use and resistance in young doctors of different specialties. METHODS: We performed an international web-based exploratory survey. Principal component analysis (PCA) and bivariate and multivariate [analysis of variance (ANOVA)] analyses were used to investigate differences between young doctors according to their country of specialization, specialty, year of training and gender. RESULTS: Of the 2366 participants from France, Greece, Italy, Portugal, Slovenia and Spain, 54.2% of young doctors prescribed antibiotics predominantly as instructed by a mentor. Associations between the variability of answers and the country of training were observed across most questions, followed by variability according to the specialty. Very few differences were associated with the year of training and gender. PCA revealed five dimensions of antibiotic prescribing culture: self-assessment of knowledge, consideration of side effects, perception of prescription patterns, consideration of patient sickness and perception of antibiotic resistance. Only the country of specialization (partial η2 0.010-0.111) and the type of specialization (0.013-0.032) had a significant effect on all five identified dimensions (P < 0.01). The strongest effects were observed on self-assessed knowledge and in the perception of antibiotic resistance. CONCLUSIONS: The country of specialization followed by the type of specialization are the most important determinants of young doctors' perspectives on antibiotic use and resistance. The inclusion of competencies in antibiotic use in all specialty curricula and international harmonization of training should be considered.

Practices, organisation, and regulatory aspects in advising on antibiotic prescription: the international ESCMID AntibioLegalMap survey.

PURPOSE: Giving advice about antibiotic prescription through dedicated consultations is a cornerstone of antibiotic stewardship programmes. Our objective was to explore practices, organisation, and regulatory requirements related to antibiotic advising. METHODS: We performed an international, exploratory, Internet-based, cross-sectional survey targeting infectious diseases and clinical microbiology specialists. It was disseminated through ESCMID and ESGAP networks. RESULTS: Answers from 830 participants (74 countries, 77% of participants from Europe) were collected. Consultations were mostly given on demand (81%, 619/764), while unsolicited consultations targeting specific conditions (e.g., positive blood culture) were less frequent (66%, 501/764). Consultations usually included indications on diagnostic work-up and follow-up (> 79%). Curbside consultations (i.e., without examining the patient) were reported by 82% (598/733) of respondents, mainly by phone (89%, 531/598). The referring physician was considered authorised not to follow the advice by 57% (383/676). Direct consultations (i.e., after examining the patient) were recorded in the medical file more frequently than curbside consultations (69%, 472/689 vs 35%, 206/592). Concerning legal liability, the majority of respondents considered that it is shared between the adviser and the referring physician, who, however, is considered primarily responsible. The advisers' liability was considered to be lower in cases of curbside and unrecorded consultations. Significant inter-countries and intra-country variability were identified, suggesting that the setting markedly influenced practices. CONCLUSION: Significant variability exists in the practice of antibiotic advising. This concerns both the organisation of care and how advisers perceive regulatory requirements. These elements must be taken into account when implementing antibiotic stewardship programmes and when training stewards.

European Antibiotic Awareness Day (EAAD): any impact on antibiotic consumption and public awareness in Slovenia?

Objectives: To evaluate the impact of European Antibiotic Awareness Day (EAAD) on antibiotic consumption, improvements in general public awareness and antibiotic resistance in Slovenia. Methods: Outpatient data for the period from 2002 to 2016 and hospital antibiotic consumption data for 2004-16 were collected using the Anatomical Therapeutic Chemical (ATC) classification/DDDs. Outpatient antibiotic consumption data were expressed in DDDs/1000 inhabitants/day (DIDs), number of packages/1000 inhabitant-days and number of prescriptions/1000 inhabitants/year. Hospital consumption data were expressed in DIDs, number of DDDs/100 bed-days and number of DDDs/100 admissions. Segmented regression analysis of interrupted time series was used to estimate the effects of these interventions on antibiotic consumption. Results: During the 8 year period since establishing EAAD, a 9%-17% decrease in outpatient antibiotic consumption has been observed, depending on the measurement unit, which was a little more than in the 6 years prior to EAAD (7%-12%). The trend change in hospital consumption after EAAD was established remained small, with a highly non-significant P value. Eurobarometer data did not show an increase in knowledge on antibiotic use. Resistance of Streptococcus pneumoniae to penicillin and macrolides decreased during EAAD activities. Conclusions: EAAD activities were associated with a decreasing trend in community consumption. Owing to many other national activities on the prudent use of antimicrobials in outpatients and inpatients it is difficult to analyse the direct effect of EAAD.

Defensive medicine among antibiotic stewards: the international ESCMID AntibioLegalMap survey.

Objectives: To investigate fear of legal claims and defensive behaviours among specialists in infectious diseases (ID) and clinical microbiology (CM) and to identify associated demographic and professional characteristics. Methods: AntibioLegalMap was an international cross-sectional internet-based survey targeting specialists in ID and CM. Three variables were explored: fear of legal liability in antibiotic prescribing/advising on antibiotic prescription; defensive behaviours in antibiotic prescribing; and defensive behaviours in advising. A multivariable logistic regression analysis was performed to identify factors significantly associated with each of the three variables. Results: Eight hundred and thirty individuals from 74 countries participated. Only 0.4% (3/779) had any kind of condemnation for malpractice related to antibiotic prescription. Concerning the fear of liability, 21.2% (164/774) of respondents said they never worried, 45.1% (349/774) sometimes worried and 28.6% (221/774) frequently worried when prescribing/advising on antibiotic prescription. Being female, younger than or equal to 35 years and aware of previous cases of litigation were independently associated with fear. Most respondents (85.0%, 525/618) reported some defensive behaviour in antibiotic prescribing. These behaviours were independently associated with being younger than or equal to 35 years and sometimes or often worried about liability. Similarly, 76.4% (505/661) reported defensive behaviours in advising. These behaviours were associated with being sometimes or often worried about liability. The preferred measures to reduce fear and defensive behaviours were having local guidelines and sharing decisions through teamwork. Conclusions: A significant proportion of specialists in ID and CM reported some form of defensive behaviour in prescribing or advising to prescribe antibiotics. Defensive medicine should be considered when implementing antibiotic stewardship programmes.

Are infection specialists recommending short antibiotic treatment durations? An ESCMID international cross-sectional survey.

Objectives: To evaluate the current practice and the willingness to shorten the duration of antibiotic therapy among infection specialists. Methods: Infection specialists giving at least weekly advice on antibiotic prescriptions were invited to participate in an online cross-sectional survey between September and December 2016. The questionnaire included 15 clinical vignettes corresponding to common clinical cases with favourable outcomes; part A asked about the antibiotic treatment duration they would usually advise to prescribers and part B asked about the shortest duration they were willing to recommend. Results: We included 866 participants, mostly clinical microbiologists (22.8%, 197/863) or infectious diseases specialists (58.7%, 507/863), members of an antibiotic stewardship team in 73% (624/854) of the cases, coming from 58 countries on all continents. Thirty-six percent of participants (271/749) already advised short durations of antibiotic therapy (compared with the literature) to prescribers for more than half of the vignettes and 47% (312/662) chose shorter durations in part B compared with part A for more than half of the vignettes. Twenty-two percent (192/861) of the participants declared that their regional/national guidelines expressed durations of antibiotic therapy for a specific clinical situation as a fixed duration as opposed to a range and in the multivariable analysis this was associated with respondents advising short durations for more than half of the vignettes (adjusted OR 1.5, P = 0.02). Conclusions: The majority of infection specialists currently do not advise the shortest possible duration of antibiotic therapy to prescribers. Promoting short durations among these experts is urgently needed.

Unilateral brachial plexopathy, a rare complication of Mycoplasma pneumoniae infection.

Few reports in the literature describe isolated peripheral neuropathies in relation to Mycoplasma pneumoniae infection without concurrent damage to the central nervous system. To our knowledge only a single case of mononeuritis multiplex with brachial plexus neuropathy coincident with M. pneumoniae has been documented until now. Here we present the first clinical case of lobar M. pneumoniae pneumonia in a 19-year-old female patient, where coincident neurological complications manifested as unilateral brachial plexus neuropathy, affecting axillar and suprascapular nerves. Isolated M. pneumoniae from sputum belonged to P1 type 2 and to MLVA type 3-6-6-2. No mutation associated with macrolide resistance in domain V of the 23S rRNA gene was detected. Serological testing of a GM1 antibody showed positive results, which might support the role of immunologic mechanisms in the pathogenesis of peripheral neuropathies related to M. pneumoniae infection.

Antimicrobial prescribing in long-term care facilities: a nationwide point-prevalence study, Slovenia, 2016.

Residents in long-term care are at high risk of infections because of their old age and many related health problems that lead to frequent antibiotic prescribing. The aim of the study was to assess antibiotic use in Slovenian long-term care facilities (LTCFs). The point-prevalence study was conducted between April and June 2016. Online questionnaires were sent to all Slovenian LTCFs. Eighty (68.4%) of the 117 LTCFs contacted, caring for 13,032 residents (70.6% of all Slovenian LTCF residents), responded to the survey. On the day of the study, the mean antibiotic prevalence per LTCF was 2.4% (95% confidence interval: 1.94-2.66). Most (70.2%) of the residents taking antibiotics were female. Most residents were being treated for respiratory tract (42.7%) or urinary tract (33.3%) infections. Co-amoxiclav and fluoroquinolones were the most frequently prescribed antibiotics (41.0% and 22.3% respectively). Microbiological tests were performed for 5.2% of residents receiving antibiotics. Forty nine (19.8%) residents receiving antibiotics were colonised with multidrug-resistant bacteria (MDR). Antibiotic use in Slovenian LTCFs is not very high, but most prescribed antibiotics are broad-spectrum. Together with low use of microbiological testing and high prevalence of colonisation with MDR bacteria the situation is worrisome and warrants the introduction of antimicrobial stewardship interventions.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms.

Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

ESGAP inventory of target indicators assessing antibiotic prescriptions: a cross-sectional survey.

Background: A variety of indicators is commonly used to monitor antibiotic prescriptions as part of national antimicrobial stewardship (AMS) programmes. Objectives: To make an inventory of indicators that assess antibiotic prescriptions and are linked to specific targets and incentives, at a national level. Methods: A cross-sectional survey (three-item questionnaire) was conducted in 2017 among all ESGAP (ESCMID Study Group for Antimicrobial stewardshiP) members, coming from 23 European countries and 16 non-European countries. Results: Almost all (20/23, 87%) European countries belonging to the ESGAP network participated, as well as one non-European country. Computerized systems routinely linking antibiotic prescriptions to clinical diagnoses were reported for only two countries (Turkey and Croatia). Only 6/21 (29%) countries had national indicators with both clear targets and incentives (Bulgaria, Croatia, France, the Netherlands, Norway and Portugal). We identified a total of 21 different indicators used in these countries, 16 concerning inpatients (9 quality indicators and 7 quantity metrics) and 8 concerning outpatients (all quantity metrics); some indicators were used in both settings. Three types of incentives were used: financing mechanism, hospitals' accreditation and public reporting. Some respondents reported that such indicators with both clear targets and incentives were used at a regional level in their country (e.g. Andalusia in Spain and England in the UK). Conclusions: National indicators, with clear targets and incentives, are not commonly used in Europe and we observed wide variations between countries regarding the selected indicators, the units of measure and the chosen targets.

Perioperative Increase in Neutrophil CD64 Expression is an Indicator for Intra-abdominal Infection after Colorectal Cancer Surgery.

BACKGROUND: Colorectal surgery is associated with a high incidence of postoperative infections. Early clinical signs are difficult to distinguish from the systemic inflammatory response related to surgical trauma. Timely diagnosis may significantly improve the outcome. The objective of this study was to compare a new biomarker index CD64 for neutrophils (iCD64n) with standard biomarkers, white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP) and procalcitonin (PCT) for the early detection of postoperative infection. METHODS: The prospective study included 200 consecutive patients with elective colorectal cancer surgery. Postoperative values of biomarkers from the postoperative day (POD) 1 to POD5 were analysed by the receiver operating characteristic (ROC) analysis to predict infection. The Cox regression model and the Kaplan-Meier method were used to assess prognostic factors and survival. RESULTS: The increase of index CD64n (iCD64n) after surgery, expressed as the ratio iCD64n after/before surgery was a better predictor of infection than its absolute value. The best 30-day predictors of all infections were CRP on POD4 (AUC 0.72, 99% CI 0.61-0.83) and NLR on POD5 (AUC 0.69, 99% CI 0.57-0.80). The best 15-day predictors of organ/space surgical site infection (SSI) were the ratio iCD64n on POD1 (AUC 0.72, 99% CI 0.58-0.86), POD3 (AUC 0.73, 99% CI 0.59-0.87) and CRP on POD3 (AUC 0.72, 99% CI 0.57-0.86), POD4 (AUC 0.79, 99% CI 0.64-0.93). In a multivariate analysis independent risk factors for infections were duration of surgery and perioperative transfusion while the infection itself was identified as a risk factor for a worse long-term survival. CONCLUSIONS: The ratio iCD64n on POD1 is the best early predictor of intra-abdominal infection after colorectal cancer surgery. CRP predicts the infection with the same predictive value on POD3.

Antituberculosis drug resistance patterns in adults with tuberculous meningitis: results of haydarpasa-iv study.

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM. METHODS: Mycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB). RESULTS: Twenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any first-line drug, the relative risk of death for INH-monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38-6.82) and 2.14 (95 % CI, 0:34-13:42), respectively. CONCLUSION: INH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing.