PURPOSE:

Colistin is increasingly used as the last-resort treatment option against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, but its nephrotoxicity is of concern, especially in severely ill patients. The aim of this study was to analyze the toxicity of colistin therapy in adults and children with hematological malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients.

METHODS:

Data on HSCT recipients and HM patients, treated with intravenous colistin (2.5-5 mg/kg/day in children and 3-6 million international units (IU) in adults, adjusted to renal function) during the period 2008-2011 in our center, were retrospectively collected and analyzed. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease).

RESULTS:

Twenty-nine children and adults received 38 courses of intravenous colistin (2.5-5 mg/kg/day in children and 3-6 × 10(6) IU in adults, adjusted to renal function) [allogeneic HSCT (22 courses) and HM (16 courses)] for 3-28 days (median 10 days) for empirical therapy for nosocomial clinical sepsis (28) or local infection (6), and bacteremia with MDR Gram-negative rods (4). Nephrotoxicity was observed at the end of 4 (10.5 %) courses. In 32 (84 %) courses, nephrotoxic medications were concomitantly administered. Two patients had convulsions, probably unrelated to colistin. Seven patients (18 %) died while on colistin therapy. No death was attributed to an adverse effect of colistin.

CONCLUSIONS:

Treatment with intravenous colistin, with dosage adjusted to renal function, was relatively safe for HM/HSCT patients, even with concomitantly administered nephrotoxic medications. Concern about nephrotoxicity should not justify a delay in initiating empirical colistin treatment in situations where infection with MDR Gram-negative rods is likely.

Malaria is often considered a cause of adult sepsis in malaria endemic areas. However, diagnostic limitations can make distinction between malaria and other infections challenging. Therefore, the objective of this study was to determine the relative contribution of malaria to adult sepsis in south-western Uganda.Adult patients with sepsis were enrolled at the Mbarara Regional Referral Hospital between February and May 2012. Sepsis was defined as infection plus ≥2 of the following: axillary temperature >37.5°C or <35.5°C, heart rate >90 or respiratory rate >20. Severe sepsis was defined as sepsis plus organ dysfunction (blood lactate >4 mmol/L, confusion, or a systolic blood pressure <90 mmHg). Sociodemographic, clinical and laboratory data, including malaria PCR and rapid diagnostic tests, as well as acid fast bacteria sputum smears and blood cultures were collected. Patients were followed until in-patient death or discharge. The primary outcome of interest was the cause of sepsis. Multivariable logistic regression was performed to assess predictors of mortality.Enrollment included 216 participants who were 51% female with a median age of 32 years (IQR 27-43 years). Of these, 122 (56%) subjects were HIV-seropositive of whom 75 (66%) had a CD4+ T cell count <100 cells/μL. The prevalence of malaria was 4% (six with Plasmodium falciparum, two with Plasmodium vivax). Bacteraemia was identified in 41 (19%) patients. In-hospital mortality was 19% (n = 42). In multivariable regression analysis, Glasgow Coma Score <9 (IRR 4.81, 95% CI 1.80-12.8) and severe sepsis (IRR, 2.07, 95% CI 1.03-4.14), but no specific diagnoses were statistically associated with in-hospital mortality.Malaria was an uncommon cause of adult sepsis in a regional referral hospital in south-western Uganda. In this setting, a thorough evaluation for alternate causes of disease in patients presenting with sepsis is recommended.

Sepsis is now the leading direct cause of maternal death in the UK and Streptococcus pyogenes the leading pathogen. We combined conventional and genomic analysis to define the duration and scale of a lethal outbreak. Two S. pyogenes post-partum deaths occurred within 24h; one characterized by bacteremia and shock, the other by hemorrhagic pneumonia. The women gave birth within minutes of each other in the same maternity unit 2d earlier. Seven additional infections in healthcare and household contacts were subsequently detected and treated. All cluster-associated S. pyogenes isolates were genotype emm1 and indistinguishable from other UK emm1 isolates. Sequencing of the virulence gene sic revealed that all outbreak isolates had the same unique sic-type. Genome sequencing confirmed the cluster was caused by a unique S. pyogenes clone. Transmission between patients occurred on a single day, and associated with casual contact only. A single isolate from one patient demonstrated a sequence change in sic consistent with longer infection duration. Transmission to healthcare workers was traced to single clinical contacts with index cases. The last case was detected 18d after the first case. Following enhanced surveillance the outbreak isolate was not detected again. Mutations in bacterial regulatory genes played no detectable role in this outbreak, illustrating the intrinsic ability of emm1 S. pyogenes to spread while retaining virulence. This fast-moving outbreak highlights S. pyogenes potential to cause a range of disease in the puerperium with rapid transmission, underlining the importance of immediate recognition and response by clinical infection and occupational health teams.

Pneumococcal infections in adults vary in severity and incidence is affected by childhood vaccination policy. Here, we try to define the host determinants and the interaction with specific serotypes that result in invasive pneumococcal disease (IPD) before an expected effect of pneumococcal conjugate vaccines. A nationwide active surveillance was initiated on July 2009, at the time of national implementation of PCV7 in Israel. The surveillance included all 27 laboratories and medical centers performing blood cultures in Israel, providing all blood and CSF pneumococcal isolates from persons ≥18y. Capture-recapture method assured that >95% of all cases were reported. IPD outcome and medical history were recorded and isolates were serotyped. Four hundred and sixty IPD cases were reported (annual incidence [/100,000] of 9.25). Incidence increased with age, from 2.6 among 18-34y to 66.8 among ≥85y. The most common diagnosis was pneumonia (72.4%), followed by bacteremia with no apparent focus (20.2%). Case fatality rate increased with age and number of comorbidities (34.5% for ≥75y or those with ≥3 comorbidities vs. 9.2-11.2% among <65y or those with no comorbidities; p=0.015). Variables independently associated with mortality were: age ≥75, chronic renal failure, malignancy, neurosurgery, alcohol abuse, multi-lobar pneumonia and sepsis with no apparent focus. The predominant serotypes in patients 18-49y were 1, 5, 8, 7F and 9V (constituting 56.3% in this age-group vs. 11.9% in ≥75y; p<0.01). The predominant serotypes among patients ≥75y were 3, 19A, 23F and 14 (40.3% of this age-group vs. 12.9% of 18-49y; p<0.01). Overall, PCV7 and PCV13 covered 25.6% and 63.7% of isolates, respectively, and 30.9% and 67.9% of isolates in mortality cases respectively. This nationwide active surveillance provides the baseline incidence, mortality rates and risk group distributions of IPD in adults before expected PCV effect.

Background:

Although extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has emerged as a significant pathogen, there is little information regarding treatment outcomes in community-onset bacteremia due to ESBL E. coli. The purpose of this study was to evaluate treatment outcomes of community-onset bacteremia caused by ESBL-producing E. coli and the factors associated with mortality.

Methods:

A retrospective cohort study was performed, including 92 adult patients with community-onset bacteremia caused by ESBL-producing E. coli.

Results:

The 30-day mortality rate was 10.9% (10/92). Independent risk factors for mortality were underlying liver disease and severity of illness (e.g., high Pitt bacteremia score, the presence of severe sepsis or septic shock; p < 0.05). Mortality in patients receiving inappropriate initial antimicrobial therapy was not significantly higher than mortality in those receiving appropriate empirical antimicrobial therapy (10.9 vs 10.7%; p = 0.975), if antimicrobial therapy was adjusted appropriately according to susceptibility results. Carbapenems, piperacillin/tazobactam, fluoroquinolones, and amikacin were the most effective antibiotics for community-onset bacteremia caused by ESBL-producing E. coli, although susceptibility profiles confirmed that alternatives to carbapenems are limited. Of 68 isolates in which the ESBLs and their molecular relationships were studied, all isolates produced ESBLs from the CTX-M family (CTX-M-14, 30 isolates; CTX-M-15, 22; and other CTX-M, 16).

Conclusions:

In patients with community-onset bacteremia caused by ESBL-producing E. coli, severe sepsis and underlying liver disease were significantly associated with mortality, and a delay in appropriate antimicrobial therapy was not associated with a higher mortality if therapy was adjusted appropriately according to the susceptibility results.

Anaplasma phagocytophilum (Dumler et al.) is the bacterial agent of human granulocytic anaplasmosis, an emerging infectious disease. The main vector of A. phagocytophilum in the United States is the blacklegged tick (Ixodes scapularis (Say)) and various small and medium-sized mammals are reservoirs. Previous studies indicate that birds are exposed to A. phagocytophilum; however, because no studies have directly investigated avian susceptibility, reservoir competence, and morbidity for A. phagocytophilum, uncertainty remains as to what role birds could play in its transmission ecology. In a controlled laboratory study, we tested whether two species, the American robin (Turdus migratorius (L.)) and the gray catbird (Dumetella carolinensis (L.)), can become infected with and then transmit A. phagocytophilum to feeding ticks, and whether exposed birds develop disease. Wild caught, seronegative birds (n = 10 per species) were exposed to A. phagocytophilum-infected I. scapularis nymphs (day 0). Transmission was assessed by xenodiagnosis on days 7, 14, 42, and 77; blood was assayed for bacteremia and serology. A. phagocytophilum was detected using quantitative polymerase chain reaction targeting the 16s rRNA gene. One robin infected 2 of 13 larval ticks (15%) on day 7; no other birds were found to infect feeding ticks at any time. Birds did not develop bacteremia, specific antibodies or significant illness because of exposure. Mouse controls became bacteremic, infected feeding ticks, and seroconverted. Our results suggest that these two avian species are unlikely to play a significant role in the maintenance of the agent of human granulocytic anaplasmosis and that avian serosurveys may not be a reliable indicator of A. phagocytophilum exposure.

Antimicrobial/host defense peptides (A/HDP) are natural compounds that are found in leucocyte cells and on the skin and bodily fluids of birds, reptiles, and mammals. Not only do they possess antibacterial, antiviral, and antiparasitic characteristics but they also stimulate the host immune system to combat infectious diseases and may play a role in the promotion of wound repair. Gamma-amino butyric acid (GABA) is an amino acid-based inhibitory neurotransmitter in the brain that has also been shown to promote wound healing on skin. The objective of this study was to establish a therapeutic cocktail that protects birds against Escherichia coli-related disease and lesions in broilers. We injected a cocktail of six A/HDPs with or without GABA into 3-wk-old broilers by a subcutaneous or intramuscular route followed 24 hr later by challenge with a field isolate of serogroup O2 E. coli. Birds were examined for 5-6 days post-E. coli challenge and clinical, pathologic, and bacteriologic assessments were conducted. Birds that were subcutaneously injected with an A/HDP plus GABA cocktail had significantly higher survival rates and lower levels of bacteremia (P < 0.05), but a similar percentage of the surviving birds had large cellulitis lesions compared to the surviving phosphate-buffered saline-injected control birds. When this cocktail was administered intramuscularly, there was a trend towards protection against E. coli-related death, although the results were not statistically significant and there was no reduction in bacteremia. A significant number of birds had a reduced bacterial load on cellulitis lesions but no reduction in lesion size, which suggests that when the cocktail was administered intramuscularly it failed to protect against cellulitis. These results suggest that the route of administration of the cocktail influences disease outcome. Gene expression analysis was performed to investigate whether the cocktail induced immunomodulatory functions in avian cells that complemented their antimicrobial and anti-endotoxic effects. A/HDP plus GABA mediated temporal induction of pro-inflammatory cytokines but no induction of any of the chemokines under investigation. This cocktail shows potential to protect against E. coli-related death, which is a major economic burden to the poultry industry.

To update and refine systematic literature review on the association between outpatient statins use and mortality in patients with infectious disease.We searched articles published before September 31, 2012, on the association between statins and infectious disease-related mortality through electronic databases. Eligible articles were analyzed in Review Manager 5.1. We conducted stratification analysis by study design, infection types, clinical outcomes and study locations.The pooled odds ratio (OR) for death (statins use vs. no use) across the 41 included studies was 0.71 (95% confidence interval: 0.64, 0.78). The corresponding pooled ORs were 0.58 (0.38, 0.90), 0.66 (0.57, 0.75), 0.71 (0.57, 0.89) and 0.83 (0.67, 1.04) for the case-control study, retrospective cohort studies, prospective cohort studies and RCTs; 0.40 (0.20, 0.78), 0.61 (0.41, 0.90), 0.69 (0.62, 0.78) and 0.86 (0.68, 1.09) for bacteremia, sepsis, pneumonia and other infections; 0.62 (0.534, 0.72), 0.68 (0.53, 0.89), 0.71 (0.61, 0.83) and 0.86 (0.70, 1.07) for 30-day, 90-day, in-hospital and long-term (>1 year) mortality, respectively.Outpatient statins use is associated with a lower risk of death in patients with infectious disease in observational studies, but in a less extent in clinical trials. This association also varies considerably by infection types and clinical outcomes.

Listeriosis is a rare food borne infection which, in the invasive form, presents as bloodstream infection, central nervous system infection, materno-fetal infection, or focal infection. Certain immunosuppressive conditions have been identified as risk factors for severe invasive disease. The invasive forms of listeriosis are associated with a high case fatality rate. We present the case of a 62-year-old male with an unremarkable medical history admitted to the Iasi Infectious Diseases Hospital for fever. headache, ataxia, and diplopia. Physical examination revealed high temperature, confusion, relative bradycardia, and signs of meningeal irritation. Laboratory test showed leukocyt osis with neutrophilia. pathological CSF findings (high WBC count with predominance of neutrophils, low glucose and high protein levels), increased liver enzymes (ALAT, ASAT, AP, gammaGT), and important renal impairment (normal levels at presentation). No abnormalities at chest x-ray, cranial CT and abdominal ultrasound. CSF and blood cultures were positive for Listeria monocytogenes. Under antibiotics (ampicillin and ciprofloxacin), the course was marked by respiratory failure requiring mechanical ventilation, coma, hypotension, tachycardia. and death 12 days after admission. The particularity of this case consists in the association of the two classical forms of invasive listeriosis, meningitis and bacteriemia, with a focal infection. acute hepatitis, and a course marked by multiple organ dysfunction syndromes and exitus in a previously apparently healthy individual.

Streptococcus pneumoniae is one of the major causative agents of invasive infectious disease in children <5 years old globally. The aim of this study was to analyze the antimicrobial resistance and the serotype distribution of S. pneumoniae isolates from the paediatric population in Tunisia and to specify the serotypes coverage by the conjugate pneumococcal vaccines. Antimicrobial susceptibility was determined by the disk diffusion method. Minimal inhibitory concentrations of beta-lactams were determined using the E test method (AB BIODISK). Serotypes were determined by agglutination of latex particles, which identified a subset of serotypes included in pneumococcal conjugate vaccines (1, 3, 4, 5, 14) and some of the serogroups. This was followed by the Neufeld test using monovalent antisera (Statens Serum Institute) specific for the other serotypes included in pneumococcal conjugate vaccines 7, 10 and 13 (PCV7, PCV10, PCV13): 6A, 6B, 7F, 9V, 18C, 19A, 19F and 23F. During the study period, 200 invasive and 310 non-invasive pneumococcal isolates were obtained from paediatric patients ranging in age from newborn to 16 years. Among these 510 isolates, 53.4% had reduced susceptibility to penicillin. Penicillin resistance was higher among S. pneumoniae isolates recovered from samples associated with non-invasive vs. invasive disease (60.6% vs. 45%). All the strains were susceptible to pristinamycin, vancomycin, teicoplanin and fosfomycin. Serotype 14 was the most frequently isolated serotype (22.2%), followed by serotypes 19F (15.5%) and 23F (10.3%). Of all strains typed, the percentage of serotypes covered by PCV7, PCV10 and PCV13 were 66.4%, 73% and 78%, respectively (76.1% for invasive pneumococcal isolates, 79.8% for non invasive pneumococcal isolates for PVC13). Continual surveillance of antibiotic susceptibility and careful use of antibiotics are recommended. The introduction of the new conjugate vaccine should be greatly beneficial for reducing pneumococcal invasive diseases among Tunisian children.