The mortality of COVID-19 in CML patients from 2020 until 2022: results from the EPICOVIDEHA survey.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Dissecting bloodstream infections in febrile neutropenic patients with hematological malignancies, a decade-long single center retrospective observational study (2009-2019).

BACKGROUND: The use of ill-suited antibiotics is a significant risk factor behind the increase in the mortality, morbidity, and economic burden for patients who are under treatment for hematological malignancy (HM) and bloodstream infections (BSI). Such unfitting treatment choices intensify the evolution of resistant variants which is a public health concern due to possible healthcare-associated infection spread to the general population. Hence, this study aims to evaluate antibiograms of patients with BSI and risk factors associated with septicemia. METHODS: A total of 1166 febrile neutropenia episodes (FNE) among 513 patients with HM from the National Center for Cancer Care and Research (NCCCR), Qatar, during 2009-2019 were used for this study. The socio-demographic, clinical, microbial, and anti-microbial data retrieved from the patient's health records were used. RESULTS: We analyzed the sensitivity of gram-negative and gram-positive bacilli reported in HM-FN-BSI patients. Out of the total 512 microorganisms isolated, 416 (81%) were gram-negative bacteria (GNB), 76 (15%) were gram-positive bacteria (GPB) and 20 (4%) were fungi. Furthermore, in 416 GNB, 298 (71.6%) were Enterobacteriaceae sp. among which 121 (41%) were ESBL (Extended Spectrum Beta-Lactamase) resistant to Cephalosporine third generation and Piperacillin-Tazobactam, 54 (18%) were Carbapenem-resistant or multidrug-resistant organism (MDRO). It's noteworthy that the predominant infectious agents in our hospital include E. coli, Klebsiella species, and P. aeruginosa. Throughout the study period, the mortality rate due to BSI was 23%. Risk factors that show a significant correlation with death are age, disease status, mono or polymicrobial BSI and septic shock. CONCLUSION: Decision pertaining to the usage of antimicrobials for HM-FN-BSI patients is a critical task that relies on the latest pattern of prevalence, treatment resistance, and clinical outcomes. Analysis of the antibiogram of HM-FN-BSI patients in Qatar calls for a reconsideration of currently followed empirical antibiotic therapy towards better infection control and antimicrobial stewardship.

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study.

Introduction: The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion: Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants' CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA).

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey.

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p < 0.001). Age, severe/critical COVID-19, ≥2 comorbidities, and lack of HM treatment were independent risk factors for mortality, whereas a lymphocyte count >500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy.

Survival Outcome of Empirical Antifungal Therapy and the Value of Early Initiation: A Review of the Last Decade.

AIM: This rapid systematic review aimed to collect the evidence published over the last decade on the effect of empirical antifungal therapy and its early initiation on survival rates. METHODS: A systematic search was conducted in PubMed, Cochrane, Medline, Scopus, and Embase, in addition to a hand search and experts' suggestions. RESULTS: Fourteen cohort studies and two randomized clinical trials reporting the survival outcome of empirical antifungal therapy were included in this review. Two studies reported the association between early empirical antifungal therapy (EAFT) and survival rates in a hematological cancer setting, and fourteen studies reported the outcome in patients in intensive care units (ICU). Six studies reported that appropriate EAFT decreases hospital mortality significantly; ten studies could not demonstrate a statistically significant association with mortality rates. DISCUSSION: The inconsistency of the results in the literature can be attributed to the studies' small sample size and their heterogeneity. Many patients who may potentially benefit from such strategies were excluded from these studies. CONCLUSION: While EAFT is practiced in many settings, current evidence is conflicting, and high-quality studies are needed to demonstrate the true value of this approach. Meanwhile, insights from experts in the field can help guide clinicians to initiate EAFT when indicated.

B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA).

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.

Epidemiology, microbiological and clinical characteristics of Enterococcus species bloodstream infections: A 10-year retrospective cohort study from Qatar.

Background and objective: Enterococcus species is one of the leading causes of community and healthcare-associated infections resulting in significant morbidity and mortality. In this study, we aim to evaluate the epidemiology, microbiological and clinical characteristics of Enterococcus Blood Stream Infections (BSIs) over 10 years period in a national secondary care setting. Methods: A retrospective cohort study was conducted on verified cases of enterococcal BSIs in adults from January 2009-December 2018 from specialized care hospitals at Hamad Medical Corporation, Qatar. Epidemiological, microbiological and clinical data were reported and analyzed. Results: A total of 263 enterococcus BSIs cases were identified, predominant were males (65%) with a median age of 63 (IQR 48-74). E. faecalis and E. faecium were predominate at 93.5% (73.38% and 20.15% respectively). Diabetes was the commonest premorbid condition (54.3%) followed by chronic kidney disease (36.5%). Central lines and genitourinary were the most common sources (18.25%, 14.83% respectively) while no identified source was reported in 45.25% of cases. Ampicillin susceptibility was 82.51% while vancomycin resistance was reported in 10.6% of isolates. Successful bacteremia clearance was achieved in 81.37% of cases at a mean of 4 days (Range 2-5 days) while metastatic complications occurred in 5.3% of cases. Univariate mortality risk analysis was associated with ICU admission, low level of consciousness, high bacteremia scores, and presence of catheters. The 30 days mortality was high at 66.54% with CKD and cancer patients at the highest mortality risks (OR 16.334 (CI 4.2-62.4) and 16 (CI 3-84) respectively. Conclusion: Significant mortality was associated with enterococcus BSI despite low rates for ampicillin and vancomycin resistance necessitating early identification of susceptible patients to instigate suitable preventive measures.

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA).

BACKGROUND: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. METHODS: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. RESULTS: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. CONCLUSIONS: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.

Ecthyma gangrenosum: a rare manifestation of Stenotrophomonas maltophilia infection in acute myelogenous leukemia patient.

Ecthyma gangrenosum is a cutaneous infection typically associated with Pseudomonas aeruginosa. However, it is rarely caused by Stenotrophomonas maltophilia which might be overlooked leading to devastating consequences. We describe this case to avoid delays in the diagnosis and treatment of this aggressive infection, especially in immunocompromised patients.

Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review.

INTRODUCTION: A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options. METHODS: Literature searches retrieved peer-reviewed publications and abstracts from major international infectious disease congresses from January 2015 to February 2021. Results were screened using pre-defined criteria to limit the dataset to relevant publications (notable exclusions were paediatric data and outcomes data for bacteria intrinsically resistant to ceftazidime-avibactam). Data for included publications were subjected to qualitative synthesis. RESULTS: Seventy-three relevant publications (62 peer-reviewed articles; 10 abstracts) comprising 1926 patients treated with ceftazidime-avibactam (either alone or combined with other antimicrobials) and 1114 comparator/control patients were identified. All patients were hospitalised for serious illness and most had multiple comorbidities. The most common infections were pneumonia, bacteraemia, and skin/soft tissue, urinary tract, or abdominal infections; smaller numbers of patients with meningitis, febrile neutropenia, osteomyelitis, and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE; n = 1718) and carbapenem-resistant, multidrug-resistant (MDR), and extensively drug-resistant Pseudomonas aeruginosa (n = 150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains. CONCLUSION: This review provides qualitative evidence of successful use of ceftazidime-avibactam for the treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.

Clinical characteristics, microbiology, and outcomes of infective endocarditis in Qatar.

BACKGROUND: Infective endocarditis (IE) is a serious and potentially life-threatening disease. The epidemiology, treatment options, and outcomes have changed considerably over the last two decades. The aim of the study was to describe the epidemiology, clinical characteristics, and outcomes of patients with IE in Qatar. METHODS: Patients were identified from Hamad Medical Corporation hospitals' electronic records, the national referral center for the State of Qatar. We included those aged ≥ 18 years with Duke Criteria-based diagnosis of IE during the period from January 2015 to September 2017. Demographic and clinical data were retrieved. Descriptive statistics were performed, and logistic regression analysis was used to describe the relationship between patient characteristics and all-cause in-hospital mortality. All potentially relevant variables were included in the univariate analysis, while those with p < 0.1 in the univariate logistic regression model were included in the multivariate analysis. For the final model, we calculated odds ratios (OR) adjusted for each of the variables included, along with their 95% confidence intervals (95% CI). Data were analyzed using STATA software version 15 (StataCorp, College Station, Texas, USA). The study was approved by the Institutional Research Board with a waiver for informed consent. RESULTS: Fifty-seven cases were included, of which 70% were males. The mean age was 51 years ( ± 16.8 years). Eleven (19%) were associated with prosthetic valves, and 6 (11%) with implantable cardiac devices. Fever (84%), dyspnea (46%), and heart failure (37%) were the most common presentations. Only 58% of patients had known preexisting valvular heart disease or an intracardiac device. Skin infections (10 patients, 18%) were the most prevalent portals of infection, followed by venous catheters, recent valve surgery, and implantable cardiac devices. Staphylococci were implicated in 19 (34%) and Streptococcaceae in 9 (16%) patients, whereas 21 (37%) patients were culture negative. Left-side IE (49 patients, 86%) was predominant. Acute kidney injury (AKI) (17 patients, 30%) and heart failure (11 patients, 19%) were common complications. The majority of patients received targeted antimicrobial therapy with at least two active agents. Only 9 (16%) patients underwent surgical intervention. Fourteen (25%) patients died of any cause before hospital discharge. Logistic regression analysis identified septic shock [OR 57.8, 95% CI 2.6-1360.2; p < 0.01] and AKI OR 33.9, 95% CI 2.9-398.1; p < 0.01) as the only risk factors independently associated with in-hospital mortality. CONCLUSION: Staphylococci are the most common microbiological cause of IE in Qatar. Surgical intervention is uncommon, and mortality is relatively high. Our findings suggest that efforts should be directed toward improving IE prevention strategies in high-risk patients, encouraging early microbiological investigations and improving medical and surgical management.

Percutaneous coronary intervention-associated Actinomyces oris.

Coronary artery interventions are safe procedures yet have a risk of stent infection, bacteremia and sepsis, events that are rare but with high morbidity and mortality sequel. A few prior cases had reported post percutaneous coronary intervention (PCI) infections, abscesses and sepsis due to Staphylococcus aureus, followed by Pseudomonas aeruginosa. Cardiac Actinomyces infections are extremely rare. Here we report a case of a 50 year old patient who developed a post intervention Actinomyces oris epicardial abscess occluding right coronary artery with subsequent bacteremia eventually requiring open heart surgery. He was treated during and thereafter with IV penicillin and ceftriaxone for almost 8 weeks. We highlight during this review the available literature regarding risk factors, the possible theories of acquiring such bacterium at this unusual site as well as our patient's course and treatment outcome.

Q-fever prosthetic valve endocarditis in a patient with SLE and antiphospholipid antibody syndrome.

Q fever prosthetic valve endocarditis in association with antiphospholipid antibody syndrome (APS) in systemic lupus erythematosus (SLE) has not been previously reported. Here, we report a 22-year-old Saudi female diagnosed with SLE and APS. She had mitral valve replacement with bio-prosthesis five years earlier for Libman-Sack endocarditis. She presented with two months' history of fever, cough, palpitations, and progressive shortness of breath. A transthoracic echocardiogram showed a degenerative mitral valve prosthesis with a large mass causing severe obstruction. Open heart surgery revealed multiple masses on the mitral valve. PCR from the resected tissues was positive for Coxiella burnetii DNA. Q fever serology showed phase two IgG 1:2048, phase one IgG 1:512, and IgM 1:1024. The valve was replaced with a bio-prosthesis. She was well at 12 months of follow-up.

Aspergillus flavus native valve endocarditis following combined liver and renal transplantation: Case report and review of the literature.

Aspergillus endocarditis is a rare infection that occurs most commonly in patients with prior cardiac surgery but cases in post-transplant recipients without prior cardiac surgery have been reported. Diagnosis is often delayed and requires high index of suspicion. We here report a case of Aspergillus endocarditis in solid organ transplant recipient.

Complications of hematopoietic stem cell transplantation: Bacterial infections.

Bacterial infections remain a common complication of hematopoietic stem cell transplantation (HSCT), especially in the pre-engraftment phase. The risk of bacterial infections is mainly related to neutropenia, mucositis, and the presence of vascular lines. Most parts of the world have witnessed a shift in epidemiology toward Gram-negative bacteria; a large proportion of which are resistant to fluoroquinolones, extended-spectrum beta-lactams, carbapenems, and in some units even colistin. Meticulous infection control practices are essential for prevention of bacterial infections in HSCT. The role of routine prophylactic antibiotics is limited in settings with high rates of bacterial resistance. If used, prophylactic antibiotics should be limited to high-risk patients, and the agents are selected based on local resistance profiles. Neutropenic fever is a medical emergency in most HSCT recipients. Prompt clinical evaluation is paramount, along with the intravenous administration of appropriate empiric antimicrobials, typically an antipseudomonal beta-lactam agent. Glycopeptides should only be considered if the patient is hemodynamically unstable or Gram-positive infection is suspected. Additional Gram-negative agents, such as colistin or aminoglycosides, may be added if extensive Gram-negative resistance is expected. To mitigate increasing bacterial resistance, empiric antibiotic regimens should be rationalized or discontinued as soon as possible.

Complications of hematopoietic stem transplantation: Fungal infections.

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients. The improved diagnostic performance of serum biomarkers such as galactomannan and ß-D-glucan, as well as polymerase chain reaction assays has allowed the development of diagnostic-driven antifungal therapy strategies for high risk patients. Diagnostic-driven approaches have resulted in reduced unnecessary antifungal exposure, improved diagnosis of invasive fungal disease, and reduced costs without increased risk of mortality. The appropriateness of diagnostic-driven antifungal strategy for individual HSCT centers depends on the availability and turnaround times for diagnostics, multidisciplinary expertise, and the local epidemiology of invasive fungal infections. Echinocandins are the treatment of choice for invasive candidiasis in most HSCT recipients. Fluconazole may be used for the treatment of invasive candidiasis in hemodynamically stable patients with no prior azole exposure. The primary treatment of choice for invasive aspergillosis is voriconazole. Alternatives include isavuconazole and lipid formulations of amphotericin. Currently available evidence does not support routine primary combination antifungal therapy for invasive aspergillosis. However, combination salvage antifungal therapy may be considered in selected patients. Therapeutic drug monitoring is recommended for the majority of HSCT recipients on itraconazole, posaconazole, or voriconazole.

Update on colistin in clinical practice.

Considerable progress has been made in the last decade towards better understanding of the optimal clinical use of colistin. It has become evident that higher intravenous (iv) colistin methanesulfonate (CMS) doses are important, probably with the addition of a loading dose in critically ill patients. Higher CMS doses lead to increased risk of nephrotoxicity, which seems reversible in most cases. Intravenous colistin is reasonably efficacious, but should continue to be considered only in the absence of safer alternatives. Although theoretically appealing, there is insufficient evidence to support inhaled colistin mono-therapy in non-cystic fibrosis patients. Moreover, the balance of evidence available at present is not in favor of adjunctive inhaled colistin therapy. Intrathecal or intra-ventricular colistin administration are appropriate options for neurosurgical meningitis caused by colistin-susceptible, multidrug resistant gram-negative bacteria. Ongoing randomized, controlled trials will hopefully help decide if combining colistin with a carbapenem, fosfomycin, or rifampicin is of clinical advantage.