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This retrospective study aimed to assess the effectiveness and safety of colistin used in combination therapy for treating nosocomial bloodstream infections caused by multi-drug resistant gram-negative pathogens in pediatric patients. Patients aged between 1 month and 18 years consecutively hospitalized with healthcare-associated bloodstream infections necessitating the administration of intravenous colistin at Dr. Sami Ulus Training and Research Hospital between January 2015 and January 2020 were included in the study. Patient-specific detailed clinical information, prognoses, and laboratory findings on days 1, 3, and 7 of colistin treatment were obtained from medical records. The study included 45 pediatric patients receiving intravenous colistin; 26 (57.8%) were male and 19 (42.2%) were female, with a median age of 18 months. While the clinical response was observed at 82.2% and microbiological response at 91.1% with colistin treatment, two patients (4.4%) discontinued treatment due to side effects without assessing treatment response. The most common adverse effect associated with the use of colistin was nephrotoxicity, which occurred in eight patients (17.8%). Among these patients, only one had pre-existing chronic kidney failure.    Conclusion: Colistin used in combination therapy may be effective and safe for treating nosocomial infections caused by multi-drug resistant gram-negative bacteria in pediatric patients, who often have high mortality rates and limited treatment options. What is Known: • Colistin is an antibacterial agent used in the treatment of infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) and is associated with significant adverse effects such as nephrotoxicity. • The increasing prevalence of hospital-acquired infections has led to the expanded use of colistin in clinical practice. What is New: • The study demonstrates a high clinical and microbiological response rate to combination therapy with colistin in the treatment of infections caused by MDR-GNB. • The study highlights the importance of monitoring nephrotoxicity in pediatric patients receiving colistin, showing that these effects can be reversible after treatment cessation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Klebsiella pneumoniae is an important opportunistic Gram-negative pathogen. This study describes an outbreak due to colistin-resistant and carbapenem-resistant Klebsiella pneumoniae (ColR-CRKP) in a tertiary hospital related to six patients successively admitted to the department of medical intensive care unit (MICU) between March 11 and April 29, 2021., Methods: Phenotypic characterization was conducted on 16 ColR-CRKP strains obtained from six infected patients and five ColR-CRKP strains isolated from 48 environmental samples, followed by whole-genome sequencing (WGS) and polymerase chain reaction (PCR) analysis., Results: All ColR-CRKP strains showed resistance to commonly used antibiotics. Whole-genome sequencing revealed a variety of resistance genes such as blaKPC-2, blaCTX-M-65, and blaTEM-4 present in all strains, which is consistent with their antimicrobial resistance profile. All isolates were identified as the high-risk sequence type 11 (ST11) clonal lineage by multilocus sequencing typing (MLST) and subsequently clustered into a single clonal type by core genome MLST (cgMLST). IS5-like element ISKpn26 family transposase insertion mutations at positions 74 nucleotides in the mgrB gene were the main cause of colistin resistance in these ColR-CRKP. The variations of genes were verified by PCR. SCOTTI analysis demonstrated the transmission pathway of the ColR-CRKP between the patients., Conclusion: Our study highlights the importance of coordinated efforts between clinical microbiologists and infection control teams to implement aggressive surveillance cultures and proper bacterial genotyping to diagnose nosocomial infections and take control measures. Routine surveillance and the use of advanced sequencing technologies should be implemented to enhance nosocomial infection control and prevention measures., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Colistin, a cationic polypeptide antibiotic of the polymyxin class has come back into use due to its potent antimicrobial activity against multidrug-resistant Gram-negative bacteria and the lack of new antibiotics. The purpose of this study was to assess the critically ill infants treated with colistin in our neonatal intensive care unit and to identify predisposing factors for the emergence of acute kidney injury (AKI) following colistin treatment., Methods: This was a retrospective case-control study that included infants with proven or suspected nosocomial infections in the neonatal intensive care unit of a University Hospital between January 2012 and March 2022. Over the same time period, the clinical and laboratory characteristics and outcomes of patients who received antibiotic combination with colistin were compared to patients who received antibiotic combination without colistin., Results: A total of 77 patients were in the colistin group (ColG) and 77 patients were in the control group. The demographic and clinical characteristics of the study groups were similar. In the ColG compared to the control group, hyponatremia, hypokalemia, hypophosphatemia, hypomagnesia and AKI were all more prevalent ( P < 0.05). The most important finding in our study was the higher incidence of AKI and mortality in ColG, as well as the increasing nephrotoxic effect of other medications when used in conjunction with colistin., Conclusion: During colistin therapy, newborn infants must be closely monitored for AKI. Clinicians should be aware of an increased incidence of hyponatremia, hypokalemia, hypophosphatemia, hypomagnesia, AKI and its consequences in infants given colistin. As awareness increases, harmful effects will decrease., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Nosocomial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a growing threat due to the limited therapeutic choices and high mortality rate. The aim of this study was to evaluate the prognostic factors for mortality in patients with nosocomial pneumonia caused by CRGNB and the impact of colistin-based therapy on the outcomes of intensive care unit (ICU) patients. We conducted a retrospective study of the ICUs in five tertiary teaching hospitals in Taiwan. Patients with nosocomial pneumonia caused by CRGNB from January 2016 to December 2016 were included. Prognostic factors for mortality were analyzed using multivariate logistic regression. The influence of colistin-based therapy on mortality and clinical and microbiological outcomes were evaluated in subgroups using different severity stratification criteria. A total of 690 patients were enrolled in the study, with an in-hospital mortality of 46.1%. The most common CRGNB pathogens were Acinetobacter baumannii (78.7%) and Pseudomonas aeruginosa (13.0%). Significant predictors (odds ratio and 95% confidence interval) of mortality from multivariate analysis were a length of hospital stay (LOS) prior to pneumonia of longer than 9 days (2.18, 1.53-3.10), a sequential organ failure assessment (SOFA) score of more than 7 (2.36, 1.65-3.37), supportive care with vasopressor therapy (3.21, 2.26-4.56), and escalation of antimicrobial therapy (0.71, 0.50-0.99). There were no significant differences between the colistin-based therapy in the deceased and survival groups (42.1% vs. 42.7%, p = 0.873). In the subgroup analysis, patients with multiple organ involvement (> 2 organs) or higher SOFA score (> 7) receiving colistin-based therapy had better survival outcomes. Prolonged LOS prior to pneumonia onset, high SOFA score, vasopressor requirement, and timely escalation of antimicrobial therapy were predictors for mortality in critically ill patients with nosocomial CRGNB pneumonia. Colistin-based therapy was associated with better survival outcomes in subgroups of patients with a SOFA score of more than 7 and multiple organ involvement., (© 2022. The Author(s).)

Introduction and Aim: Multidrug resistance in bacteria has become a widespread scourge. The objective of this study is to investigate the epidemiology of multidrug-resistant bacteria (MDR) at Fattouma Bourguiba University Hospital of Monastir - Tunisia compared to the community and to define their antibiotic resistance profiles., Methods: It was a retrospective and descriptive study over a period of 5 years (2016-2020) conducted at the microbiology department of Fattouma-Bourguiba University Hospital of Monastir - Tunisia. All MDR strains isolated from diagnostic microbiological samples collected from patients hospitalized in high-risk infectious departments and from outpatients were included in our study., Results: A total of 4324 MDR among 16353 bacteria were isolated during the study period, i.e. a resistance rate of 26.4% with a predominance of hospital strains (80.3% versus 19.7% in the city). Third generation cephalosporin-resistant Enterobacteriaceae were the most prevalent and were mainly represented by extended-spectrum beta- lactamases (67.1% versus 83.4% in the community). Escherichia coli was the most frequent species (40.9%). It was frequently associated with resistance to fluoroquinolones (in more than 73% of cases). Imipenem-resistant Acinetobacter baumannii was mostly responsible for hospital acquired infections (77%). Co- resistances concerned most of the antibiotics but spared colistin. Methicillin-resistant Staphylococcus aureus infections were more frequent in the city (20.5% versus 19.3% in hospitals). Resistance associated was mainly to fusidic acid (49.6%). Glycopeptides have maintained their activity and only 2% were of decreased sensitivity to vancomycin., Conclusion: The emergence of MDR always represents a public health challenge. Thus, hygiene measures associated with an optimization of antibiotic therapy are necessary for a better control of their diffusion.

Objective: To compare the effectiveness and safety of aerosolized (AER) plus intravenous (IV) colistin with IV colistin alone in patients with nosocomial pneumonia (NP) due to multidrug-resistant (MDR) Gram-negative bacteria., Methods: This was a retrospective cohort study of adults with NP who received IV colistin alone or in combination with AER colistin. The primary endpoint was clinical cure at end of therapy. Secondary endpoints included microbiological eradication, in-hospital mortality and nephrotoxicity., Results: In total, 135 patients were included in this study: 65 patients received AER plus IV colistin and 70 patients received IV colistin alone. Baseline characteristics were similar between the two groups. Clinical cure was achieved in 42 (65%) patients who received AER plus IV colistin and 26 (37%) patients who received IV colistin alone (P = 0.01). Among a total of 88 patients who were microbiologically evaluable, 27 (42%) patients who received AER plus IV colistin and 12 (17%) patients who received IV colistin alone attained favourable microbiological outcomes (P = 0.022). In-hospital mortality (43% vs 59%, P = 0.072) was higher in patients who received IV colistin alone, but the difference was not significant. Renal injury occurred in 31% of patients who received AER plus IV colistin and in 41% of patients who received IV colistin alone (P = 0.198)., Conclusion: AER colistin can be considered as salvage therapy as an adjunct to IV administration for the treatment of patients with NP due to MDR Gram-negative pathogens., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Colistin and carbapenem-resistant Acinetobacter calcoaceticus- Acinetobacter baumannii complex (CCR-Acb complex) was isolated from two consecutive patients in the neurological intensive care unit (NICU). An urgent reaction to this desperate situation was required., Patients and Methods: Screening cultures were taken from the other patients sharing the NICU with index patients and repeated periodically. NICU was closed for new admissions. Infection control precautions (ICP) such as hand hygiene, cohorting patients colonized with CCR-Acb complex, cohorting the staff caring for these patients, daily bathing with chlorhexidine gluconate impregnated clothes, using gowns when contacting with patients and patient care area, and sodium hypochlorite tablets for environmental cleaning were enforced., Results: Screening cultures revealed carbapenem-resistant Acb complex in 12 out of 32 patients and 8 of them were colonized with CCR-Acb complex. NICU was opened for new admissions one month later. No further new cases with CCR-Acb complex were detected by screening cultures after 6 weeks with enforcement of ICP. Moreover, the rate of nosocomial infections caused by other multi-drug resistant Gram-negative bacilli (MDR-GNB) decreased significantly when rates before and after closing the NICU were compared., Conclusion: ICP were effective not only to limit the spread of CCR-Acb complex but also decreased the incidence of other MDR-GNB infections when applied adequately., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pseudomonas aeruginosa cross-infections are related to increased morbidity and mortality in cystic fibrosis (CF)., Objectives: The aim of the study was to evaluate the incidence of cross-infections with P. aeruginosa in children with CF., Methodology: CF patients from whom at least one P. aeruginosa strain had been isolated were included in the study. The strain genotyping was performed using pulse-field gel electrophoresis. The history of contacts between patients was established based on questionnaires., Results: The study group consisted of 75 patients (aged 1.0-19.2 years) and the material included 170 P. aeruginosa strains. Cross-infections occurred in a group of 26 patients. In this group, the risk of the predicted occurrence of forced expiratory volume in 1 second ≤ 70% was five times greater and the risk of longer cumulative hospitalization time for intravenous antibiotic therapy (>14 days/year) was almost five times greater. In the clonal groups of strains, the multidrug-resistance rate was significantly higher than in other groups. In 2011, all tested strains were susceptible to colistin, whereas in 2012, three strains from the largest clonal group showed high levels of resistance to colistin., Conclusion: Cross-infections with P. aeruginosa occurred in our group of patients and were associated with poor clinical outcomes. Antimicrobial resistance rate in the strains isolated from such infections was significantly higher, and this included three strains resistant to colistin., (© 2019 Wiley Periodicals, Inc.)

Objective: To determine the cost-effectiveness of selective digestive decontamination (SDD) as compared to selective oropharyngeal decontamination (SOD) in intensive care units (ICUs) with low levels of antimicrobial resistance., Design: Post-hoc analysis of a previously performed individual patient data meta-analysis of two cluster-randomised cross-over trials., Setting: 24 ICUs in the Netherlands., Participants: 12 952 ICU patients who were treated with ≥1 dose of SDD (n=6720) or SOD (n=6232)., Interventions: SDD versus SOD., Primary and Secondary Outcome Measures: The incremental cost-effectiveness ratio (ICER; ie, costs to prevent one in-hospital death) was calculated by comparing differences in direct healthcare costs and in-hospital mortality of patients treated with SDD versus SOD. A willingness-to-pay curve was plotted to reflect the probability of cost-effectiveness of SDD for a range of different values of maximum costs per prevented in-hospital death., Results: The ICER resulting from the fixed-effect meta-analysis, adjusted for clustering and differences in baseline characteristics, showed that SDD significantly reduced in-hospital mortality (adjusted absolute risk reduction 0.0195, 95% CI 0.0050 to 0.0338) with no difference in costs (adjusted cost difference €62 in favour of SDD, 95% CI -€1079 to €935). Thus, SDD yielded significantly lower in-hospital mortality and comparable costs as compared with SOD. At a willingness-to-pay value of €33 633 per one prevented in-hospital death, SDD had a probability of 90.0% to be cost-effective as compared with SOD., Conclusion: In Dutch ICUs, SDD has a very high probability of cost-effectiveness as compared to SOD. These data support the implementation of SDD in settings with low levels of antimicrobial resistance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background The emergence and rapid spread of multidrug-resistant gram-negative bacteria related to nosocomial infections is a growing worldwide problem, and polymyxins have become important due to the lack of new antibiotics. Objectives To evaluate the outcomes and pharmacoeconomic impact of using colistin and polymyxin B to treat nosocomial infections. Setting Neurosurgical, cardiovascular, or transplantation intensive care unit (ICU) at the Clinical Hospital of the University of Campinas (São Paulo, Brazil). Method A retrospective cohort study was conduct in patients in the ICU. The renal function was determined daily during treatment by measuring the serum creatinine. A cost minimization analysis was performed to compare the relative costs of treatment with colistin and polymyxin B. Main outcomes measure The outcomes were 30-day mortality and frequency and onset of nephrotoxicity after beginning treatment. Results Fifty-one patients treated with colistin and 51 with polymyxin B were included. 30-day mortality was observed in 25.49% and 33.33% of patients treated with colistin and polymyxin B, respectively; Nephrotoxicity was observed in 43.14% and 54.90% of patients in colistin and polymyxin B groups, respectively; and onset time of nephrotoxicity was 9.86 ± 13.22 days for colistin and 10.68 ± 9.93 days for polymyxin B group. Colistin treatment had a lower cost per patient compared to the cost for polymyxin B treatment (USD $13,389.37 vs. USD $13,639.16, respectively). Conclusion We found no difference between 30-day mortality and nephrotoxicity between groups; however, colistin proved to be the best option from a pharmacoeconomic point of view.

Rationale: Acinetobacter baumannii is one of the antibiotic-resistant superbugs that threatens hospitalized patients. Emergence and spread of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) clones cause erratic outbreaks following environmental contamination of hospital settings., Objective: The present study intended to characterize the antimicrobial resistant profiles and the genotypes of clinical and environmental isolates of A. baumannii as a result of dissemination of resistant strains., Methods: Clinical and environmental isolates of A. baumannii were obtained from patients, staff, and environment of an educational hospital in Tehran. Antimicrobial susceptibility testing was carried out using the disk diffusion and E-test methods. Multiplex PCR was performed for detection of OXA-type genes (bla OXA-23-like , bla OXA-24-like , bla OXA-58-like , and bla OXA-51-like ). Genotypic relatedness of the isolates was achieved using repetitive extragenic palindromic element PCR (Rep-PCR) technique., Results: All the isolates were found to be susceptible to colistin and most of them (77%) were non-susceptible to tigecycline. A majority of the clinical and environmental isolates (97%) were considered as MDR strains and 41% as XDR. In multiplex detection, bla OXA-23-like was found in 54% of the isolates, which was the most frequent OXA-type gene. In addition, the frequency of the carbapenem-resistant A. baumannii (CRAB) was observed to be high (96%). In addition, molecular typing showed different Rep patterns of clinical isolates and clonal spread of environmental isolates., Conclusion: The present study highlights the circulation of drug-resistant A. baumannii strains in different wards of hospitals principally in intensive care unit (ICU) as a nosocomial pathogen due to unwise managements., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against Enterobacteriaceae and Pseudomonas aeruginosa isolates from patients in the Asia-Pacific (APAC) region with healthcare-associated infections. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. A total of 1963 Gram-negative organisms (489 P. aeruginosa and 1474 Enterobacteriaceae) were consecutively collected using a prevalence-based approach from 14 medical centres in the APAC region. Antimicrobial susceptibility testing was performed by broth microdilution method as described by the CLSI and the results were interpreted according to EUCAST and CLSI breakpoint criteria. Ceftolozane/tazobactam [MIC 50/90 , 0.25/4 µg/mL; 89.2/85.8% susceptible (CLSI/EUCAST)] and meropenem [MIC 50/90 , ≤0.06/≤0.06 µg/mL; 96.3/96.5% susceptible (CLSI/EUCAST)] were the most active compounds tested against Enterobacteriaceae. Isolates displayed susceptibility rates to other β-lactam agents ranging from 85.8/81.0% for piperacillin/tazobactam to 74.4/72.7% for cefepime and 72.8/68.1% for ceftazidime using CLSI/EUCAST breakpoints. Among the Enterobacteriaceae isolates, 3.6% were carbapenem-resistant Enterobacteriaceae (CRE) and 25.6% exhibited an extended-spectrum β-lactamase (ESBL) non-CRE phenotype. Ceftolozane/tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacteriaceae (MIC 50/90 , 0.5/16 µg/mL), but not against isolates with a CRE phenotype (MIC 50/90 , >32/>32 µg/mL). Ceftolozane/tazobactam was the most potent (MIC 50/90 , 0.5/4 µg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 90.8% at an MIC of ≤4 µg/mL. Pseudomonas aeruginosa exhibited high rates of susceptibility to amikacin [91.2/89.4% (CLSI/EUCAST)] and colistin [98.4/100.0% (CLSI/EUCAST)]. Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins when tested against Enterobacteriaceae., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: The aim of this study was to assess the safety and efficacy of colistin use in critically ill neonates., Methods: This was a case-control study that included newborn infants with proven or suspected nosocomial infections between January 2012 and October 2015, at two centers in Diyarbakir, Turkey. The clinical and laboratory characteristics and outcomes of patients who received colistin therapy were reviewed and compared to patients who were treated with antimicrobial agents other than colistin during the same period., Results: Forty-seven cases who received intravenous colistin (colistin group) and 59 control patients (control group) were included. There were no significant differences between the groups regarding outcomes and nephrotoxicity, including acute renal failure. Colistin therapy was associated with significantly reduced serum magnesium (1.38 ± 0.39 mg/dL vs. 1.96 ± 0.39 mg/dL, p < 0.001) and hypokalemia (46.8% vs. 25.4%, p = 0.026). The patients who received colistin also had longer hospital stays (43 (32-70) days vs. 39 (28-55) days, p = 0.047), a higher rate of previous carbapenem exposure (40.4% vs. 11.9%, p = 0.001), and a higher age at the onset of infection (13 (10-21) days vs. 11 (9-15) days, p = 0.03)., Conclusion: This study showed that colistin was both effective and safe for treating neonatal infections caused by multidrug-resistant gram-negative bacteria. However, intravenous colistin use was significantly associated with hypomagnesemia and hypokalemia., (Copyright © 2017. Published by Elsevier B.V.)

Stenotrophomonas maltophiliais an emerging cause of nosocomial infections. We report an outbreak of XDR-Stenotrophomonas maltophilia infection from burn unit of a tertiary care hospital in July 2016. The strain isolated was resistant to all antimicrobials tested but colistin. Outbreak investigation was carried out which subsided after timely intervention. Patients were treated adequately by Colistin.

To assess risk factors for recurrent carbapenem-resistant Klebsiella pneumoniae bloodstream-infection (CR-KP BSI), we performed a prospective observational cohort study of all consecutive adult patients cured of a CR-KP BSI at our hospital over a six-year period (June 2010 to June 2016). Maximum follow-up per patient was 180 days from the index blood cultures (BCs). Recurrent CR-KP BSI was defined as new evidence of positive BCs in patients with documented clinical response after completing a course of anti-CR-KP therapy. Univariate and multivariate cause-specific Cox proportional hazards analysis were performed. During the study period 249 patients were diagnosed with a CR-KP BSI, 193 were deemed as cured within 14 days after index BCs and were analysed. Recurrence occurred in 32/193 patients (16.6%) within a median of 35 (IQR 25-45) days after index BCs. All but one of the recurrences occurred within 60 days after the index BCs. Comparison of recurrent and non-recurrent cases showed significant differences for colistin use (84.4% vs. 62.2%, p = 0.01), meropenem-colistin-tigecycline regimen (43.8% vs. 24.8%, p = 0.03) and length of therapy for the index BSI episode (median 18 vs. 14 days, p = 0.004). All-cause 180-day mortality (34.4% vs. 16.1%, p = 0.02) was higher in recurrent cases. In the multivariate analysis, the only independent variable was source control as a protective factor for recurrence. Recurrence is frequent among patients cured of a CR-KP BSI and is associated with higher long-term mortality. When feasible, source control is mandatory to avoid recurrence. The role of antibiotic treatment should be further investigated in large multicentre studies.

Background: Infection caused by carbapenem-resistant Acinetobacter baumannii (CRAB) has become a major problem in intensive care units (ICUs), with high incidence and mortality. This prospective study investigated the diagnostic value and influence of active surveillance, followed by isolation and enhanced contact precaution (IECP), on the subsequent CRAB infection and colistin use., Methods: The study prospectively enrolled 1,115 patients who were admitted to the medical ICU of Chonnam National University Hwasun Hospital between April 2011 and November 2014. Active surveillance cultures were obtained from the throat or trachea, skin, and urine. IECP was performed beginning April 2013., Results: Active surveillance detected CRAB in 168 (15%) patients and CRAB infection developed in 70 (6%) patients. Endotracheal tube was independently associated with both CRAB colonization and infection, whereas IECP was inversely associated with both CRAB colonization and infection in multivariate analysis (all P values <.001). The sensitivity, specificity, and positive and negative predictive values of active surveillance for subsequent CRAB infection were 84%, 90%, 47%, and 98%, respectively. The rate of CRAB acquisition, CRAB infection, and the use of colistin were significantly lower during the IECP period compared with the control period (6.5 vs 34.1, 2.6 vs 14.7, and 19.9 vs 65.5 per 1,000 patient-days, respectively; all P <.001)., Conclusions: Active surveillance has good specificity and negative predictive value for subsequent CRAB infection. Active surveillance followed by IECP was inversely associated with the acquisition of CRAB and subsequent CRAB infection, and was associated with a reduction in colistin use in ICU patients., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Klebsiellapneumoniae is a significant pathogen associated with hospital infections. Its was isolated in intensive care units (ICU) at two pediatric hospitals in Moscow in 2012-2014 from 41% (387/935) of the patients. The rate of carbapenem-nonsusceptibility (Carba-NS) amounted to 25% for imipenem and 27% for meropenem. For further analyses, 67 isolates were selected, including 57 Carba-NS and 10 Carba-susceptible (Carba-S). Among the isolates, 100% was nonsusceptible to the III-IV generation cephalosporins, 50-84% was resistant to aminoglycosides. The rate of nonsusceptibility to ciprofloxacin and phosphomycin exceeded 90%. All the tested Carba-S Kpneumoniae isolates were susceptible to tigecycline, whereas 25% of the Carba-NS isolates was tigecycline-NS. The prevalence of the colistin-NS isolates was the same in Carba-S (20%) and Carba-NS (26%) bacteria. The blamrx&#95; gene was carried by 100% of the Carba-S isolates, combining with the blaTEM gene in 60% of the isolates. In 89% of the Carba-NS isolates the OXA-48 carbapenemase was detected, which was combined with CTX-M and/or TEM in all but 1 isolate. Thus, over the last decade, the rate of Carba-NS among nosocomial Kpneuynoniae increased and the OXA-48 carbapenemase was shown to be dominating in the mechanism of Carba-NS in the pediatric ICUs in Moscow.

We report the emergence and analysis of a cluster of concurrent infections/colonisations with colistin-resistant Klebsiella pneumoniae and OXA-23 carbapenemase-producing Acinetobacter baumannii in patients who had undergone cardiac surgery. We describe the emergence of colistin-resistant K. pneumoniae harbouring blaCTX-M-15, blaSHV-11, blaOXA-1, blaTEM-1 beta-lactamases and aac(6')-Ib-cr fluoroquinolone resistance. Colistin-resistant K. pneumoniae infections (pneumonia, wound infection, urinary tract infections and bacteraemia) occurred in critically ill patients previously treated with colistin for post-surgery infections with carbapenem-resistant Pseudomonas aeruginosa and/or A. baumannii. Although the cause of death could not be directly attributed to a single pathogen, three patients co-infected/colonised with K. pneumoniae, P. aeruginosa and/or A. baumannii died, whilst a fourth patient who had a mono-microbial infection with colistin-resistant K. pneumoniae only survived. The use of mobile intubation equipment in patients that shared the same ward, the clustering of cases over a short period of time, as well as the pulsed-field gel electrophoresis (PFGE) data all suggest cross-contamination between patients, either through equipment or by staff contact transmission. This report presents the 'worst-case scenario' where concurrent infection/colonisation with pathogens exhibiting resistance to different types of last-resort antimicrobials occurred in some of the most debilitated intensive care unit (ICU) patients.

The global spread of multi-drug resistant organisms (MDRO) is a major threat to public health. Fighting MDRO spread requires a multi-faceted approach as summarized in the German Antibiotic Resistance Strategy (DART). In the hospital, this includes antibiotic stewardship concepts and strict infection control measures. Treatment of MDRO is sophisticated. Within the last years, several antibiotics with activity against MRSA were launched and facilitate an individual therapy according to site of infection and co-morbidities. In contrast, novel antibiotics against carbapenemase producing Gram-negatives are still lacking. Current studies have shown, that a colistin-based combination treatment can improve the prognosis in these patients. The following article reviews MDRO definitions, burden of disease, treatment options and general strategies against MDRO., (© Georg Thieme Verlag KG Stuttgart · New York.)

We report three cases of external ventricular derivation infections caused by multidrug-resistant Gram-negative rods and treated successfully with intraventricular colistin. The intrathecal or intraventricular use of colistin have been reported in more than 100 cases without any consensus on dosage, duration and type (monotherapy or combination therapy) of treatment. Based on our comprehensive review of the relevant literature relating to both clinical and pharmacokinetic data, we conclude that the intrathecal/intraventricular administration of colistin is a safe and effective option to treat central nervous system infections caused by multidrug-resistant Gram-negative bacteria.

Carbapenem-resistant Acinetobacter baumannii isolates were obtained from 50 patients between July 2011 and July 2012 at the University Hospital A Coruña (NW Spain). These multidrug-resistant isolates, which belonged to a single clone, remained only susceptible to tigecycline, minocycline, and colistin and produced the carbapenem-hydrolyzing oxacillinase, OXA-23. This is the first reported outbreak of OXA-23-producing A. baumannii isolates in Spain.

Increasing use of colistin for multidrug-resistant Gram-negative bacterial infections has led to the emergence of colistin resistance in Klebsiella pneumoniae in several countries worldwide, including Europe (especially Greece), and colistin resistance rates are continually increasing. Heteroresistance rates, which were significantly higher than resistance rates, were found to be important. Although the mechanism underlying resistance is unclear, it has been suggested that it is related to lipopolysaccharide modification via diverse routes. Several factors have been reported as being associated with colistin resistance, with improper use and patient-to-patient transmission being most often cited. Total infections and infection-related mortality from colistin-resistant K. pneumoniae are high, but currently there are no established treatment regimens. However, several combination regimens that are mainly colistin-based have been found to be successful for treating such infections., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: Colistin is active against most multidrug-resistant, aerobic Gram-negative bacteria. Because of the reported nephrotoxicity during the first years of use of colistin, there were concerns of its use in pediatrics where there was limited experience The aim of this study is to document the clinical characteristics and outcomes of use of colistin in pediatric patients at a pediatric intensive care unit in Turkey., Methods: We reviewed the medical and laboratory records of 29 critically ill children who were treated with colistin for 38 courses between January 2011 and December 2011 at the Department of Pediatric Intensive Care Unit in Ankara University Medical School, Turkey., Results: The median age was 17 months (range 3-217 months). Male-to-female ratio was 1:1.37. Ventilator-associated pneumonia (21 courses) was the leading diagnosis followed by catheter-related blood stream infection (6 courses), bacteremia (4 courses), ventriculoperitoneal shunt infection, peritonitis and pneumonia (1 course). The most commonly isolated microorganisms were Acinetobacter baumanni, Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens, Stenotrophomonas maltophilia, and Enterobacter cloacae. Two colistin formulations were used. Colimycin (Kocak Farma) was used in 21 colistin treatment episodes. The median dosage of colistin in this group was 5.0 mg/kg/d (2.3-5.6 mg/kg/d). Colomycin (Forest Laboratories) was used in 17 colistin treatment episodes. The median dosage of colistin in the second group was 75,000 International Unit/kg/d (50,000-80,000 International Unit/kg/d). Thirty colistin treatment episodes (79%) had a good or partial clinical response and 8 (21%) had a poor clinical response. Of the 8 colistin treatment episodes with poor clinical response, 3 were in the Colimycin group and 5 were in the Colomycin group. Ten patients died. There was no evidence of neurotoxicity in this study. Nephrotoxicity was observed in 1 patient but was not attributed to colistin because the patient had multiorgan failure at the same time., Conclusions: This study in a small cohort of patients suggests that the use of colistin in severe nosocomial infections caused by multidrug-resistant Gram-negative bacteria is well-tolerated and efficacious.

Nosocomial infections and their rational antibiotic treatment represent a major challenge for the healthcare nowadays. In this context, gramnegative bacteria including Pseudomonas aeruginosa, Acinetobacter baumanii and Enterobacteriaceae spp. are etiologically important and characterized by a significant level of antibiotic resistance. To examine dynamics of the respiratory tract colonization by hospital flora, tracheal aspirates obtained at three time points from 69 children with severe craniocerebral trauma during their stay in ICU were analysed. Colonization was observed on the 4th day of the ICU stay with predomination of K. pneumoniae (45%) and A. baumanii (27-37%). P. aeruginosa was detected after the 8th day of the ICU stay with the isolation rate of 33%. Substantial proportions of P. aeruginosa (61%), A. baumanii (78%) and K. pneumoniae (25%) were resistant to carbapenems. In 65 carbapemen resistant isolates, the presence of carbapenemases was examined using PCRs. OXA-48 carbapenemase was detected in 11 out of 14 (78%) K. pneumoniae isolates. Among the A. baumanii isolates, 30/31 (97%) carried OXA-40 and 1/31 (3%) had OXA-23 carbapenemases. None of the examined A. baumanii and K. pneumoniae isolates produced metallo-betalactamases (MBL). In contrast, all 20 carbapenem resistant P. aeruginosa isolates produced a MBL, and in 12 out of 20 (60%) of theme VIM-2 was detected. Thus, gramnegative nosocomial microflora rapidly colonizes ICU patients and has a high level of resistance to antibiotics, including carbapenems.

Background: The aim of this study was to investigate the efficacy and safety of colistin therapy in pediatric patients with severe nosocomial infections in pediatric intensive care unit., Methods: The medical records of patients treated with colistin at a 200-bed university children hospital were reviewed., Result: Thirty-one patients (male/female = 22/9; median age, 3 years; range, 3 months-17 years) received forty-one courses of colistin. The average dose of colistin was 4.9 ± 0.5 mg/kg/day and average treatment duration was 19.8 ± 10.3 days. Three patients who received concomitant nephrotoxic agent with colistin developed nephrotoxicity. Colistin treatment was well tolerated in other patients, and neurotoxicity was not seen in any patient. Favourable outcome was achieved in 28 (68.3%) episodes. Twelve patients died during the colistin therapy. Six of these patients died because of primary underlying disease. The infection-related mortality rate was found 14.6% in this study., Conclusion: In our study, colistin therapy was found to be acceptable treatment option for the severe pediatric nosocomial infections caused by multi-drug resistant bacteria. However, the use of concomitant nephrotoxic drugs with colistin must be avoided and renal function test should be closely monitored.

Objective: To describe a single center experience involving the administration of colistin to treat nosocomial infections caused by multidrug-resistant Gram-negative bacteria and identify factors associated with acute kidney injury and mortality., Methods: This retrospective longitudinal study evaluates critically ill patients with infections caused by multidrug-resistant Gram-negative bacteria. All adult patients who required treatment with intravenous colistin (colistimethate sodium) from January to December 2008 were considered eligible for the study. Data include demographics, diagnosis, duration of treatment, presence of acute kidney injury and 30-day mortality., Results: Colistin was used to treat an infection in 109 (13.8%) of the 789 patients admitted to the intensive care unit. The 30-day mortality observed in these patients was 71.6%. Twenty-nine patients (26.6%) presented kidney injury prior to colistin treatment, and six of these patients were able to recover kidney function even during colistin treatment. Twenty-one patients (19.2%) developed acute kidney injury while taking colistin, and 11 of these patients required dialysis. The variable independently associated with the presence of acute kidney injury was the Sequential Organ Failure Assessment at the beginning of colistin treatment (OR 1.46; 95%CI 1.20-1.79; p<0.001). The factors age (OR 1.03; 95%CI 1.00-1.05; p=0.02) and vasopressor use (OR 12.48; 95%CI 4.49-34.70; p<0.001) were associated with death in the logistic-regression model., Conclusions: Organ dysfunction at the beginning of colistin treatment was associated with acute kidney injury. In a small group of patients, we were able to observe an improvement of kidney function during colistin treatment. Age and vasopressor use were associated with death.

Objectives: Nosocomial infection due to multidrug-resistant Gram-negative pathogens in ICUs is a challenge for clinicians and microbiologists and has led to the resurgence of IV colistin use in the last decade. The aim of this study was to assess the efficacy of IV colistin in the treatment of critically ill children with multidrug-resistant Gram-negative infections., Design and Setting: Retrospective descriptive study conducted in the PICU of Maulana Azad Medical College and associated Chacha Nehru Bal Chikitsalaya, Delhi, India, during the period of January 2010 to December 2011., Patients: The records of critically ill children with multidrug-resistant Gram-negative infections treated with IV colistin were reviewed., Results: Fifty critically ill children received IV colistin; their median age was 36 months (range: 1 mo-12 yr), with male:female ratio of 3:2. The isolated pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. Mean duration of colistin therapy was 14.3 days (range, 7-21). A favorable clinical outcome occurred in 36 children (72%), and 14 children (28%) died due to severe sepsis with multiple-organ dysfunction syndrome. Renal toxicity occurred in five children and was associated with multiple-organ dysfunction syndrome in three and coadministration of vancomycin in two. No neurotoxic adverse effects due to colistin therapy were reported., Conclusion: Our study suggests that IV colistin may have a role in the treatment of infections caused by multidrug-resistant Gram-negative bacteria in critically ill children, but further prospective and randomized control trials are needed to confirm its efficacy and safety in children.

Serratia marcescens causes health care-associated infections with important morbidity and mortality. Particularly, outbreaks produced by multidrug-resistant isolates of this species, which is already naturally resistant to several antibiotics, including colistin, are usually described with high rates of fatal outcomes throughout the world. Thus, it is important to survey factors associated with increasing frequency and/or emergence of multidrug-resistant S. marcescens nosocomial infections. We report the investigation and control of an outbreak with 40% mortality due to multidrug-resistant S. marcescens infections that happened from November 2007 to April 2008 after treatment with colistin for Acinetobacter baumannii meningitis was started at hospital H1 in 2005. Since that year, the epidemiological pattern of frequently recovered species has changed, with an increase of S. marcescens and Proteus mirabilis infections in 2006 in concordance with a significant decrease of the numbers of P. aeruginosa and A. baumannii isolates. A single pulsed-field gel electrophoresis (PFGE) cluster of S. marcescens isolates was identified during the outbreak. When this cluster was compared with S. marcescens strains (n = 21) from 10 other hospitals (1997 to 2010), it was also identified in both sporadic and outbreak isolates circulating in 4 hospitals in Argentina. In132::ISCR1::blaCTX-M-2 was associated with the multidrug-resistant cluster with epidemic behavior when isolated from outbreaks. Standard infection control interventions interrupted transmission of this cluster even when treatment with colistin continued in several wards of hospital H1 until now. Optimizing use of colistin should be achieved simultaneously with improved infection control to prevent the emergence of species naturally resistant to colistin, such as S. marcescens and P. mirabilis.

Background: Acinetobacter species are well-known causes of health care-associated infections. The longitudinal epidemiology of this species in the hospital setting is poorly understood. A sudden, persistent increase in multidrug-resistant (MDR) A baumannii infections occurred beginning in June 2006 at Temple University Hospital in Philadelphia. An analysis was done to describe the longitudinal molecular epidemiology of MDR A baumannii in a tertiary care hospital., Methods: This was an epidemiologic investigation using repetitive extragenic palindromic-PCR (rep-PCR) of patients with a positive culture for MDR A baumannii admitted to the hospital between February 2006 and January 2010. MDR A baumannii were defined as susceptible only to colistin and/or tigecycline., Results: The incidence rate of MDR A baumannii rose from 0.36 cases per 1,000 patient-days (pre-epidemic) to 0.86 cases per 1,000 patient-days, due mainly to an increase in the surgical intensive care unit. Enhanced infection control measures were implemented, but waves of MDR A baumannii continued to be documented through routine surveillance. Of 32 strains collected in 2006-2007, a single predominant clone and 2 minor clones accounted for almost all of the cases of MDR A baumannii studied. Of 24 strains collected in 2008-2009, another clone, different from those studied in the earlier period, predominated, and was accompanied by 3 minor variants., Conclusion: Following an outbreak in the surgical intensive care unit, MDR A baumannii persisted in our institution for a 3-year period despite rigorous infection control measures. An unexpected strain replacement occurred during this period, with the original predominant strain disappearing completely and new minor clones displacing the original minor clones., (Published by Mosby, Inc.)

Hospital-acquired pneumonia is a common complication that continues to have a poor cure rate in some patients with intravenous therapy alone. Aerosolized antibiotics are theoretically attractive in an attempt to optimize lung concentrations of antibiotics. Limited data suggest that aerosolized aminoglycosides or colistin in addition to intravenous therapy results in good response rates in patients with multidrug-resistant organisms or nonresponding pneumonia. Adverse events can occur, especially with colistin. When used, care should be taken to properly compound and administer aerosolized antibiotics to ensure tolerability and good drug delivery.

Purpose: Multidrug-resistant Acinetobacter baumannii (MRAB) is an emerging cause of intensive care unit (ICU) outbreaks. Patients are the main reservoirs, inducing cross transmission. We describe an MRAB outbreak that occurred in the Prato Hospital ICU in June to August 2009., Materials and Methods: The ICU consists of 2 separated 4-bed rooms (rooms A and B). The MRAB-positive patients were included in our study. During the outbreak, infection control measures were enhanced; patients and environmental screenings were performed. A 6-month follow-up was carried out., Results: Four of 26 patients admitted during the outbreak were MRAB positive. All patients were located in room A; no case was detected in room B either in the hospital or during the follow-up. Management included closure to new admissions, reinforcement of infection control measures, patient and environmental screenings, discharge of room B MRAB-negative patients for at least 5 days after the first case identification. All isolates were carbapenems resistant and tigecycline and colistin susceptible. All patients received tigecycline: 2 were successfully treated, 1 died because of preexisting illness, and 1 developed resistance and recovered after colistin therapy., Conclusions: Enhanced infection control measures and adequate antibiotic strategy limited the outbreak. Tigecycline allowed rapid recovery. Nevertheless, resistance ensued; so colistin remained the only therapeutic option. However, pan-drug resistance has been reported., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Acinetobacter baumannii is an opportunistic Gram-negative pathogen with increasing relevance in a variety of hospital-acquired infections especially among intensive care unit patients. Resistance to antimicrobial agents is the main reason for A. baumannii spread. A. baumannii outbreaks described worldwide are caused by a limited number of genotypic clusters of multidrug-resistant strains that successfully spread among hospitals of different cities and countries. In this article, we will focus on the mechanisms responsible for resistance to antimicrobials and disinfectants in A. baumannii and the epidemiology of drug-resistant A. baumannii in healthcare facilities. We will also discuss the therapeutic and infection control strategies for management of drug-resistant A. baumannii epidemics.

Importance of the Field: Although colistin has recently played a key role in the treatment of nosocomial infections due to multidrug resistant Gram-negative pathogens, there is a lack of clinical studies examining colistin pharmacokinetics (PKs) in humans. This refers to all routes of colistin administration in clinical practice. Colistin PK data are also limited in critically ill patients., Areas Covered in This Review: Literature search took into account data dealing with colistin PK obtained from animal studies performed during previous decades (1970s, 1980s and 1990s) and from recent human studies performed during the last decade., What the Reader Will Gain: Valuable information on pharmacodynamics (PD)/PK of colistin used in the treatments of nosocomial infections due to multidrug resistant Gram-negative pathogens, mostly Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. A better understanding of PKs could offer significant improvement of colistin use in humans, especially optimization of colistin doses in different routes of administration in order to maximize clinical efficacy and minimize adverse effects and rate of resistance., Take Home Message: There is a lack of human studies on colistin PK and PD. Significant PD parameters best predicting colistin efficacy and their optimal values such as C(max):MIC ratio, AUC/MIC and T > MIC have not yet been clearly defined. It should be noted that further investigation on colistin PK/PD in vitro and in vivo models is required.

Emergence of multidrug-resistant Gram-negative nosocomial pathogens has led to resurgence of colistin use. Safety and efficacy data regarding colistin use in pediatric patients are sparse, while optimal dosage has not been defined. We present a case series of neonates and children without cystic fibrosis treated with various doses of colistin intravenously. The records of patients who received colistin in a tertiary-care hospital from January 2007 to March 2009 were reviewed. Thirteen patients (median age 5 years, range 22 days to 14 years) received 19 courses of colistin as treatment of pneumonia, central nervous system infection, bacteremia, or complicated soft tissue infection. The isolated pathogens were Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. Daily dose of colistin (colistimethate) ranged between 40,000 and 225,000 IU/kg. Duration of administration ranged from 1 to 133 days. Other antimicrobials were co-administered in 18/19 courses. Increase of serum creatinine in one patient was associated with co-administration of colistin and gentamicin. Sixteen of 19 courses had a favorable outcome, and only two of the three deaths were infection-related. Colistin intravenous administration appears well tolerated even at higher than previously recommended doses and of prolonged duration.

Aim: The aim of the present study was to assess the efficacy and safety of colistimethate sodium therapy in multidrug-resistant nosocomial infections caused by Pseudomonas aeruginosa or Acinetobacter baumannii in neonates and children., Methods: Pediatric patients hospitalized at the Uludag University Hospital who had nosocomial infections caused by multidrug-resistant P. aeruginosa or A. baumannii, were enrolled in the study. Colistimethate sodium at a dosage of 50-75 x 10(3) U/kg per day was given i.v. divided into three doses., Results: Fifteen patients received 17 courses of colistimethate sodium for the following infections: ventilator-associated pneumonia (n= 14), catheter-related sepsis (n= 1) and skin and soft-tissue infection (n= 2). The mean age of patients was 53.2 + 74.7 months (range, 8 days-15 years) and 60% were male. Mortality was 26.6%., Conclusion: Colistimethate sodium appears to be safe and effective for the treatment of severe infections caused by multidrug-resistant P. aeruginosa or A. baumannii in pediatric patients.

Background: Colistin has re-entered clinical use by necessity. We aimed to assess its effectiveness and safety compared with newer antibiotics., Methods: This was a single-centre, prospective cohort study. Inclusion criteria were microbiologically documented pneumonia, urinary tract infection, surgical site infection, meningitis or bacteraemia treated appropriately with colistin versus imipenem, meropenem or ampicillin/sulbactam (comparators). All consecutive patients were included, only once, between May 2006 and July 2009. The primary outcome was 30 day mortality. Multivariable and Cox regression survival analyses were used to adjust comparisons between groups. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals are reported., Results: Two hundred patients treated with colistin and 295 patients treated with comparators were included. Treatment with colistin was associated with older age, admission from healthcare facilities, mechanical ventilation and lower rate of early appropriate antibiotic treatment. The 30 day mortality was 39% (78/200) for colistin versus 28.8% (85/295) for comparators; unadjusted OR 1.58 (1.08-2.31). In the adjusted analysis the OR was 1.44 (0.91-2.26) overall and 1.99 (1.06-3.77) for bacteraemic patients (n = 220). At the end of follow-up, treatment with colistin was significantly associated with cumulative mortality; adjusted HR 1.27 (1.01-1.60) overall and 1.65 (1.18-2.31) among patients with bacteraemia. Nephrotoxicity at the end of treatment was more frequent with colistin; OR adjusted for other risk factors for nephrotoxicity 3.31 (1.54-7.08). Treatment with colistin was followed by increased incidence of Proteus spp. infections during a 3 month follow-up., Conclusions: The need for colistin treatment is associated with poorer survival. Adjusted analyses suggest that colistin is less effective and more toxic than beta-lactam antibiotics.

Aim: To analyze the clinical features, evolution and treatment of nosocomial staphylococcal meningitis admitted to Hospital of Infectious Diseases Iaşi between 1988 and 2007., Material and Method: The data were gathered from the archive of Hospital of Infectious Diseases Iaşi. We studied the clinical and laboratory features of 62 cases of nosocomial staphylococcal meningitis admitted in the study period., Results: The development of nosocomial meningitis was subsequent to interventions on the central nervous system for haematoma, ventriculo-peritoneal shunts, tumors, spinal anesthesia. The symptoms were fever, headache, stiff neck and vomiting. The etiological agents were: Staphylococcus aureus 37 in cases and coagulase negative staphylococci in 25 cases. The treatment was according to their susceptibility rates, using systemic quinolones and ceftazidime or colymicin. The evolution was favorable in 52 patients and unfavorable in another 10., Conclusion: Nosocomial staphylococcal meningitis remains a serious condition due to the fact that the etiological agents are resistant to the classical antistaphylococcal antibiotics and increasingly resistant to methicillin.

Colistin heteroresistance in Acinetobacter baumannii (Ab) has been reported, but the clinical impact and the antimicrobial treatment have not been established yet. We observed the selection intratreatment with colistin of Ab colistin-resistant strains from a colistin-heteroresistant isolate in one patient with postneurosurgical meningitis. The presence and the genetic relationship of heteroresistant Ab isolates from intensive care units (ICUs) obtained in the same period of the case report were analyzed. Twenty-eight isolates from patients admitted to the ICUs of an Argentinian university hospital during June to December 2004 were evaluated. Genomoespecie was determined by amplified ribosomal DNA restriction analysis, and genetic similarity among the strains was determined by pulsed-field electrophoresis. Colistin heteroresistance was observed in 46, 4% of these isolates. The majority belonged to clones previously identified as I and III.

Aim: To analyze the clinical features, etiology and evolution of nosocomial bacillary meningitis admitted to the Clinic of Infectious Diseases Iaşi between 1988 and 2007., Material and Method: The data were gathered from the archive of the Clinic of Infectious Diseases Iaşi. We studied the clinical and laboratory features of 28 cases of nosocomial bacillary meningitis admitted in the study period., Results: The development of nosocomial meningitis was subsequent to interventions on the central nervous system for hematoma, ventriculo-peritoneal shunts, tumors, rah anesthesia. The symptoms were fever, headache, stiff neck and vomiting. The etiological agents were: Acinetobacter spp--35.71%, Pseudomonas spp.--25%, Klebsiella pneumoniae--17.85%, Escherichia coli--14.28%, and mixed etiology, in 3.57% of the cases each. The treatment was according to their susceptibility, using systemic quinolones and ceftazidime or colymicin. The evolution was favorable in 13 patients and unfavorable in another 15., Conclusion: Nosocomial meningitis caused by Gram negative bacilli is a severe infection, with diverse etiology, which raises therapeutical problems due to antibiotic resistance and a high mortality rate.

Background: Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and efficacy with other antimicrobials., Methods: A retrospective cohort study of patients treated with colistin or tobramycin for A. baumannii infections in intensive care units (ICUs) at Groote Schuur hospital. Colistin was used for A. baumannii isolates which were resistant to all other available antimicrobials. In the tobramycin group, 53% of the isolates were only susceptible to tobramycin and colistin. We assessed ICU mortality, nephrotoxicity and time to the first negative culture., Results: 32 patients, with similar admission APACHE scores and serum creatinine, were treated with each antimicrobial. There were no significant differences between the colistin and tobramycin groups in ICU mortality (p=0.54), nephrotoxicity (p=0.67), change in creatinine from baseline to highest subsequent value (p=0.11) and time to microbiological clearance (p=0.75). The hazard ratio for total in-hospital survival in patients treated with colistin compared to tobramycin was 0.43 (95% CI 0.19 to 0.99)., Conclusion: Our study suggests that colistin and tobramycin have similar risks of nephrotoxicity and are equally efficacious. Colistin is an acceptable antibiotic for the treatment of A. baumannii infections when the organism is resistant to other available antimicrobials.

Background: The nosocomial spread of pan-antibiotic-resistant nonfermentative bacteria is an increasing concern. This study investigated the microbiologic and epidemiologic characteristics of a hospital outbreak due to alginate-producing, pan-antibiotic-resistant Pseudomonas aeruginosa (PAR-Pa)., Methods: All patients with infection with a P. aeruginosa strain that was resistant to all Clinic Laboratory Standards Institute-suggested antimicrobial agents between November 2004 and May 2005 were included in the study. Alginate production detection and pulsed-field gel electrophoresis (PFGE) typing were done for the patient and environmental surveillance isolates. A matched case-control study was performed to identify risk factors and evaluate outcomes., Results: PFGE analysis of a total of 35 PAR-Pa isolates (28 patient and 7 environmental surveillance isolates) identified a single epidemic clone as responsible for the outbreak. All epidemic isolates were alginate-producing and susceptible only to colistin. The Student t-test demonstrated that a longer stay in the intensive care unit (ICU) (6.64 days vs 1.83 days; P < .05) significantly increased the risk of PAR-Pa infection. Systemic PAR-Pa infection resulted in higher mortality (85.7% vs 27.8%; P < .05). Multivariate analysis determined that therapeutic failure (odds ratio = 24.7; 95% confidence interval = 4.144 to 147.221; P < .05) was the independent risk factor related to this high mortality. Localized PAR-Pa infections were associated with longer hospital stays (46.2% vs 14.4%; P < .05) and higher rates of surgery (85.7% vs 15.4%; P < .05) and amputation (42.8% vs 0%; P < .05). The recovery of the pathogen from staff hands and frequently handled surfaces suggests possible handborne transmission. Improved hygienic standards and application of strict contact precautions, including isolation, reduced the spread of the pathogen., Conclusion: This study illustrates the ability of pan-antibiotic-resistant P. aeruginosa to cause an outbreak with significant mortality and stresses the need for precautions to prevent the spread of such highly resistant strains.