Development of Meropenem Resistance in a Multidrug-Resistant Campylobacter coli Strain Causing Recurrent Bacteremia in a Hematological Malignancy Patient.

Campylobacter bacteremia is an uncommon disease that mainly occurs in immunocompromised patients and is associated with antibiotic resistance, particularly in Campylobacter coli. We report a patient with persistent blood infection because of a multidrug-resistant (MDR) C. coli strain over a 3-month period. Through this period monotherapy with meropenem was associated with the development of resistance to it. Improving immunity status and a combined therapy for intestinal decolonization were useful to control persistent C. coli infection in this patient.

Impact of Empirical Antibiotic Regimens on Mortality in Neutropenic Patients with Bloodstream Infection Presenting with Septic Shock.

We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. A multicenter retrospective study (2010 to 2019) of two prospective cohorts compared BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Of 1,563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% versus 15%, P < 0.001). Gram-negative bacilli caused 81% of episodes with septic shock, Gram-positive cocci caused 22%, and Candida species caused 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical ß-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific Gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% versus 51%, P = 0.002). Age of >70 years (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2 to 4.7), IEAT for Candida spp. or Gram-negative bacilli (OR, 3.8; 95% CI, 1.3 to 11.1), acute kidney injury (OR, 2.6; 95% CI, 1.4 to 4.9), and amikacin as the only active antibiotic (OR, 15.2; 95% CI, 1.7 to 134.5) were independent risk factors for mortality, while the combination of ß-lactam and amikacin was protective (OR, 0.32; 95% CI, 0.18 to 0.57). Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active ß-lactam and amikacin results in the best outcomes.

Inappropriate Empirical Antibiotic Treatment in High-risk Neutropenic Patients With Bacteremia in the Era of Multidrug Resistance.

BACKGROUND: We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality. METHODS: This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes. RESULTS: Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19-4.91]), shock at onset (4.62 [2.49-8.56]), and pneumonia (3.01 [1.55-5.83]). CONCLUSIONS: IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa-related BSI mortality and in turn is the only modifiable factor to improve outcomes.

A Randomized, Double-Blind, Placebo-Controlled Trial (TAURCAT Study) of Citrate Lock Solution for Prevention of Endoluminal Central Venous Catheter Infection in Neutropenic Hematological Patients.

Infection of long-term central venous catheters (CVCs) remains a challenge in the clinical management of cancer patients. We aimed to determine whether a lock solution with taurolidine-citrate-heparin would be more effective than placebo for preventing nontunneled CVC infection in high-risk neutropenic hematologic patients. We performed a prospective, multicenter, randomized (1:1), double-blind, parallel, superiority, placebo-controlled trial involving 150 hematological patients with neutropenia carrying nontunneled CVCs who were assigned to receive CVC lock solution with taurolidine-citrate-heparin or heparin alone. The primary endpoint was bacterial colonization of the CVC hubs. Secondary endpoints were the incidence of catheter-related bloodstream infection (CRBSI), CVC removal, adverse events related to the lock solution, and the 30-day case fatality rate. CVC lock solution with taurolidine-citrate-heparin was associated with less colonization of the CVC hubs than that with placebo, with no statistically significant differences: 4.1%, versus 10.1% (relative risk [RR] = 0.41, 95% confidence interval [CI] = 0.11 to 1.52), with a cumulative incidence of 4.17 (95% CI = 0.87 to 11.70) and 10.14 (95% CI = 4.18 to 19.79), respectively. There were no significant differences regarding the secondary endpoints. Only three episodes of CRBSI occurred during the study period. No adverse events related to the administration of the lock solution occurred. In this trial involving high-risk patients carrying nontunneled CVCs, the use of taurolidine-citrate-heparin did not show a benefit over the use of placebo. Nevertheless, the safety of this prevention strategy and the trend toward less hub colonization in the taurolidine-citrate-heparin group raise the interest in assessing its efficacy in centers with higher rates of CRBSI. (This study has been registered in ISRCTN under identifier ISRCTN47102251.).

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990-2017.

INTRODUCTION: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. METHODS: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. RESULTS: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990-1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71-9.25), 0.70 (0.13-3.85), and 1.29 (0.28-5.91) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990-1996 period, the odds ratios and 95% CIs were 0.80 (0.09-7.22); 1.94 (0.21-17.96), and 2.42 (0.25-23.07) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. CONCLUSION: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.

An Ocean between the Waves: Trends in Antimicrobial Consumption in Hospitalized Patients with COVID-19.

We assessed the antibiotic use in SARS-CoV-2-infected patients during four different waves of the COVID-19 pandemic, as well as its trends over the period and associated risk factors. We performed a cross-sectional retrospective analysis nested in a prospectively collected cohort of hospitalized adult patients with COVID-19 at a university hospital in Spain. A total of 2415 patients were included in this study, among whom 1120 corresponded to the first wave. The highest percentage of patients receiving some sort of antibiotic treatment was higher during the first wave (77.6%) than during the others; nevertheless, our calculation of the average DOT (days of antibiotic treatment) per 100 patient days of stay found that the highest antibiotic prescription rate corresponded to the second pandemic wave (61.61 DOT/100 patient days), which was associated with a higher ICU admission rate and a lower SpO2/FiO2 ratio at admission. After the second wave, the prescription rates presented a steady downward trend. With regard to the use of specific antibiotic families, amoxicillin/clavulanate was the most used antibiotic in our cohort (14.20 DOT/100 patient days) due to a high prescription rate during the first wave. According to the "AWaRe" WHO classification, antibiotics corresponding to the "Watch" group were the most prescribed (27.92 DOT/100 patient days). The antibiotic use rate fell progressively, but it remained high during all four waves analyzed. In conclusion, antibiotic use was high throughout all the waves that were analyzed, despite a relatively low incidence of bacterial coinfection and superinfection. Efforts should be made to keep antimicrobial stewardship programs active, especially in complicated epidemiological situations, such as the SARS-CoV-2 pandemic.

Efficacy of extended infusion of ß-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomised, multicentre, open-label, superiority clinical trial.

OBJECTIVES: The efficacy of extended infusions (EI) of ß-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of ß-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia. METHODS: We performed a randomised, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of ß-lactam or II after a first dose in bolus. The choice of antipseudomonal ß-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50, 75 and 100%ƒuT>MIC, and 30-day mortality. RESULTS: Between November 19, 2019 and June 22, 2022, 295 patients we screened for eligibility, of whom 150 were randomly assigned to receive EI (n=77) or II (n=73) of the antipseudomonal ß-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference -12.4%; 95% confidence interval, -29.4 to 4.7, p=0.17). The pharmacokinetic/pharmacodynamic targets of 75 and 100% ƒuT>MIC for empirical treatment were achieved more frequently in the EI group. No statistically-significant differences were found between groups in terms of adverse events or 30-day mortality. CONCLUSIONS: Our findings do not support the routine use of empirical EI of ß-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis/septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to ß-lactams.

Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Increasing Gram-Negative Catheter-Related Bloodstream Infection in Cancer Patients.

Background: We aimed to assess the incidence, etiology and outcomes of catheter-related bloodstream infection (CRBSI) in onco-hematological patients, to assess the differences between patients with hematological malignancies (HMs) and solid tumors (STs) and to identify the risk factors for Gram-negative (GN) CRBSI. Methods: All consecutive episodes of BSI in adult cancer patients were prospectively collected (2006-2020). The etiology of CRBSI was analyzed in three different 5-year periods. Risk factors for GN CRBSI were assessed in the whole cohort and separately in patients with HMs and STs. Results: Among 467 episodes of monomicrobial CRBSI, 407 were Gram-positive (GP) (87.1%), 49 GN (10.5%) and 11 fungal (2.4%). Hematological patients (369 episodes) were more frequently neutropenic and were more likely to carry central venous catheters and develop GP CRBSI. Patients with STs (98 episodes) had more comorbidities, more frequently carried port reservoirs and commonly presented more GN CRBSI. GN CRBSI significantly increased over the study period, from 5.2% to 23% (p < 0.001), whereas GP CRBSI decreased from 93.4% to 73.3% (p < 0.001). CRBSI episodes involving port reservoirs and peripherally-inserted central catheters were significantly increased (p < 0.001). The most frequent GPs were coagulase-negative staphylococci (CoNS) (57.8%) and Pseudomonas aeruginosa was the most common GN (3%). Multidrug-resistant (MDR) GN represented 32.7% of all GN CRBSIs and increased over time (p = 0.008). The independent risk factors for GN CRBSI in the whole cohort were solid tumor, chronic kidney disease and carrying a port reservoir. Carrying a port reservoir was also a risk factor in patients with STs. Health-care acquisition was identified as a risk factor for GN CRBSI in the whole cohort, as well as in patients with STs and HMs. Inadequate empirical antibiotic treatment (IEAT) occurred regardless of the etiology: 49% for GNs and 48.6% for GPs (p = 0.96). In GP CRBSI, IEAT was mainly due to inadequate coverage against CoNS (87%), whereas in GN CRBSI, IEAT was associated with multidrug resistance (54.2%). Early (48 h and 7-day) and 30-day case-fatality rates were similar when analyzed according to the type of underlying disease and etiology, except for the 30-day case-fatality rate, which was higher in the group of patients with STs compared to those with HMs (21.5% vs. 12.5%, p = 0.027). The 48 h case-fatality rate was significantly higher in patients in whom the catheter had not been removed (5.6% vs. 1%; p = 0.011), and it remained significant for GP CRBSI (6% vs. 1.3%, p = 0.023). Conclusions: GNs are an increasing cause of CRBSI in cancer patients, particularly in solid tumor patients carrying port reservoirs. Multidrug resistance among GNs is also increasing and is associated with higher rates of IEAT. Decreased 48 h survival was associated with the non-removal of the catheter. These findings should be considered when deciding on early therapeutic management for cancer patients with suspected CRBSI.

The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients.

OBJECTIVES: to assess the current epidemiology, antibiotic therapy and outcomes of onco- hematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. METHODS: episodes of bacteremic SSTIs occurring in cancer patients at two hospitals were prospectively recorded and retrospectively analyzed. RESULTS: Of 164 episodes of bacteremic SSTIs, 53% occurred in patients with solid tumors and 47% with hematological malignancies. GNB represented 45.5% of all episodes, led by Pseudomonas aeruginosa (37.8%). Multidrug resistance rate was 16%. Inadequate empirical antibiotic therapy (IEAT) occurred in 17.7% of episodes, rising to 34.6% in those due to resistant bacteria. Independent risk factors for GNB infection were corticosteroid therapy and skin necrosis. Early and overall case-fatality rates were 12% and 21%, respectively. Risk factors for early mortality were older age, septic shock, and IEAT, and for overall mortality were older age, septic shock and resistant bacteria. CONCLUSIONS: GNB bacteremic SSTI was common, particularly if corticosteroid therapy or skin necrosis. IEAT was frequent in resistant bacteria infections. Mortality occurred mainly in older patients with septic shock, resistant bacteria and IEAT. These results might guide empirical antibiotic therapy in this high-risk population.

Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study.

OBJECTIVES: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies. METHODS: BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions. RESULTS: 121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most frequent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 100-day mortality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases. CONCLUSIONS: BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.

Bloodstream Infection and Endocarditis Caused by Staphylococcus aureus in Patients with Cancer: A Multicenter Cohort Study.

INTRODUCTION: In a large cohort of patients with Staphylococcus aureus bloodstream infection (SABSI), we aimed to analyze the incidence and risk factors for infective endocarditis (IE) among patients with active cancer (PAC) in comparison with those without cancer (PWC). METHODS: Multicenter cohort study of patients with SABSI admitted to two tertiary care hospitals, from 2011 to 2019. PAC were defined as those with an active solid organ cancer or hematological malignancies. SABSI and S. aureus IE were compared between PAC and PWC. RESULTS: Among 978 episodes of SABSI, 217 (22.2%) occurred in PAC. PAC were younger, had fewer comorbidities, carried cardiac devices less often, and had less community-acquired SABSI than PWC. Compared to PWC, PAC more frequently had catheter-related SABSI, less IE (2.8% vs 10.9%, p < 0.001) and osteoarticular infection (2.3% vs 14.3%, p < 0.001). Independent risk factors for IE were cardiopathy (aOR 4.392, 95% CI 2.719-7.094) and persistent bacteremia (aOR 3.545, 95% CI 2.159-5.820). Thirty-day mortality was high, and similar between groups (24.2% vs 25.5%, p = 0.282). CONCLUSIONS: PAC with SABSI developed IE less frequently than PWC did. This finding seems related to the differences in baseline characteristics and may have significant clinical implications, such as transesophageal echocardiography in PAC without cardiopathy or persistent bacteremia.

Real-Life Use of Ceftolozane/Tazobactam for the Treatment of Bloodstream Infection Due to Pseudomonas aeruginosa in Neutropenic Hematologic Patients: a Matched Control Study (ZENITH Study).

We sought to assess the characteristics and outcomes of neutropenic hematologic patients with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) treated with ceftolozane-tazobactam (C/T). We conducted a multicenter, international, matched-cohort study of PA BSI episodes in neutropenic hematologic patients who received C/T. Controls were patients with PA BSI treated with other antibiotics. Risk factors for overall 7-day and 30-day case fatality rates were analyzed. We compared 44 cases with 88 controls. Overall, 91% of episodes were caused by multidrug-resistant (MDR) strains. An endogenous source was the most frequent BSI origin (35.6%), followed by pneumonia (25.8%). There were no significant differences in patient characteristics between groups. C/T was given empirically in 11 patients and as definitive therapy in 41 patients. Treatment with C/T was associated with less need for mechanical ventilation (13.6% versus 33.3%; P = 0.021) and reduced 7-day (6.8% versus 34.1%; P = 0.001) and 30-day (22.7% versus 48.9%; P = 0.005) mortality. In the multivariate analysis, pneumonia, profound neutropenia, and persistent BSI were independent risk factors for 30-day mortality, whereas lower mortality was found among patients treated with C/T (adjusted OR [aOR] of 0.19; confidence interval [CI] 95% of 0.07 to 0.55; P = 0.002). Therapy with C/T was associated with less need for mechanical ventilation and reduced 7-day and 30-day case fatality rates compared to alternative agents in neutropenic hematologic patients with PA BSI. IMPORTANCE Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited. Our study is unique because it is focused on extremely immunosuppressed hematological patients with neutropenia and bloodstream infection (BSI) due to PA (mainly multidrug resistant [MDR]), a scenario which is often associated with very high mortality rates. In our study, we found that the use of C/T for the treatment of MDR PA BSI in hematological neutropenic patients was significantly associated with improved outcomes, and, in addition, it was found to be an independent risk factor associated with increased survival. To date, this is the largest series involving neutropenic hematologic patients with PA BSI treated with C/T.

Effect of Combination Antibiotic Empirical Therapy on Mortality in Neutropenic Cancer Patients with Pseudomonas aeruginosa Pneumonia.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01−2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27−0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76−2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990–2017 / Mortalidad y secuelas de la meningitis tuberculosa en Barcelona (España): Estudio de cohortes, 1990-2017

Introduction: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. Methods: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. Results: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990–1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71–9.25), 0.70 (0.13–3.85), and 1.29 (0.28–5.91) for the 1997–2003, 2004–2010, and 2011–2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990–1996 period, the odds ratios and 95% CIs were 0.80 (0.09–7.22); 1.94 (0.21–17.96), and 2.42 (0.25–23.07) for the 1997–2003, 2004–2010, and 2011–2017 periods respectively. Conclusion: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.(AU)

Introducción: La meningitis tuberculosa (TBM), la forma más grave de tuberculosis, provoca una alta mortalidad y discapacidad a largo plazo en países con bajos recursos. Nuestro objetivo es investigar la tendencia temporal de la mortalidad y las secuelas en un país con recursos elevados y baja incidencia. Métodos: Hemos realizado un estudio de cohortes retrospectivo de los pacientes adultos con TBM en dos hospitales universitarios de tercer nivel en Barcelona (España), entre 1990 y 2017, evaluando las tendencias temporales de mortalidad y secuelas a los 12 meses, comparando cuatro periodos consecutivos de siete años. Las tasas observadas en los cuatro periodos se han ajustado por covariables. Resultados: De los 135 casos incluidos, todos menos uno inició tratamiento antituberculoso y 120 (89,6%) recibieron rifampicina, isoniazida y pirazinamida, con o sin etambutol. La probabilidad de estar vivo a los 12 meses fue de 81,8%, sin diferencias entre los cuatro periodos: en comparación con el periodo 1990-1996, los coeficientes de riesgo ajustados y los intervalos de confianza (IC) del 95% fueron 2,55 (0,71-9,25), 0,70 (0,13-3,85) y 1,29 (0,28-5,91) para los periodos 1997-2003, 2004-2010 y 2011-2017, respectivamente. Las secuelas estaban presentes en 28,3% en el mes 12, sin diferencias entre los cuatro periodos en el análisis ajustado: en comparación con el periodo 1990-1996, los coeficientes de probabilidad y los IC 95% fueron 0,80 (0,09-7,22); 1,94 (0,21-17,96) y 2,42 (0,25-23,07) para los periodos 1997-2003, 2004-2010 y 2011-2017, respectivamente. Conclusión: Este estudio muestra que la TBM todavía causa una alta mortalidad y discapacidad sin mejoría con el tiempo, incluso en un entorno con baja incidencia de tuberculosis y con elevados recursos.(AU)