Background: In view of the paucity of clinical evidence, in vitro studies are needed to find antibiotic combinations effective against multidrug-resistant Gram-negative bacteria. Interpretation of in vitro effects is usually based on bacterial growth after 24h in time-kill and checkerboard experiments. However, the clinical relevance of the effects observed in vitro is not established. In this study we explored alternative output parameters to assess the activities of colistin and meropenem against Pseudomonas aeruginosa and Acinetobacter baumannii.Methods: Four strains each of P. aeruginosa and A. baumannii were exposed to colistin and meropenem, alone and in combination, in 8h dynamic time-kill experiments. Initial (1h), maximum and 8h bacterial reductions and the area under the bacterial time-kill curve were evaluated. Checkerboards, interpreted based on fractional inhibitory concentration indices after 24h, were performed for comparison.Results: In the time-kill experiments, the combination resulted in enhanced 1h, maximum and 8h bacterial reductions against 2, 3 and 5 of 8 strains, respectively, as compared to the single drugs. A statistically significant reduction in the area under the time-kill curve was observed for three strains. In contrast, the checkerboards did not identify synergy for any of the strains.Conclusions: Combination effects were frequently found with colistin and meropenem against P. aeruginosa and A. baumannii in time-kill experiments but were not detected with the checkerboard method. We propose that the early dynamics of bacterial killing and growth, which may be of great clinical importance, should be considered in future in vitro combination studies.
The aim of this study was to investigate the prevalence and characteristics of resistant Klebsiella pneumoniae isolates in the pediatric setting in China. A total of 201 non-duplicate K. pneumoniae isolates were obtained from 432 pediatric inpatients suffering from respiratory tract infections. One hundred and thirty-eight K. pneumoniae isolates were determined to be extended-spectrum beta-lactamase-producers. Of all ESBL-producing isolates, 138 (100%) were resistant to piperacillin, ampicillin, cefazolin, and aztreonam, 136 (98.4%) to cefuroxime, 126 (91.2%) to ceftriaxone and co-trimoxazole, 120 (87.4%) to cefoperazone, 91 (65.8%) to ceftazidime, 78 (56.5%) to gentamicin, and 72 (52.4%) to cefepime. TEM was the main type of beta-lactamase among ESBL-producing K. pneumoniae, followed by SHV and CTX-M-1. Of the 30 isolates harboring CTX-M-producers, 53.3% co-produced TEM, 36.7% co-produced SHV, and the remaining isolates co-produced SHV and TEM. The data show that there is a high prevalence of ESBL-producing K. pneumoniae infections among pediatric inpatients in the region.
Abstract Laryngeal tuberculosis (TB) was a common manifestation of TB in the early twentieth century, but now represents only 1% of all cases. Most modern case series of laryngeal TB originate outside the USA. We report a case of laryngeal TB from our institution and review other US cases published between 1970 and 2012. One hundred twenty-seven cases were identified. The mean patient age was 49 y and 28% were female. The mean duration of symptoms was 19 weeks. Dysphonia and weight loss were the most common manifestations, seen in 96% and 47% of cases, respectively. These symptoms were usually attributed to malignancy initially. Most cases involved the vocal cords. Eighty-six percent of cases had underlying pulmonary involvement. Mortality was 3%. In the USA, laryngeal TB is rarely suspected and often confused with malignancy. This infection should be considered in patients with unexplained dysphonia and weight loss.
To the Editor,The article entitled “Vertebral osteomyelitis: Retrospective review of 11 years of experience” [1], is an excellent retrospective study that emphasizes the staphylococcal etiology as ...
The report by De Jong et al. [1] of several cases of Raoultella bacteremia associated with biliary disease was interesting to us as we recently encountered a similar patient. A 66-y-old woman with unresectable pancreatic cancer was admitted with nausea, emesis, increasing weakness, and neutropenic fever several days after beginning her second cycle of FOLFOX chemotherapy (folinic acid, fl uorouracil, and oxaliplatin). There was no history of fl ushing or recent fi sh ingestion. Other than a temperature of 39 ° C, her physical examination (including abdominal examination) was unremarkable. Her absolute neutrophil count was 150 cells/mm 3 . An abdominal computed tomogram did not reveal abscess or air. Empiric antibiotic therapy with piperacillin – tazobactam 3.375 g intravenously every 6 h was begun. Blood cultures obtained at admission grew Raoultella ornithinolytica and Escherichia coli. Subsequent blood cultures demonstrated clearing of both organisms. Despite this apparent response to treatment of her infection, her condition continued to deteriorate and her family opted for palliative care. She died 18 days after admission. While reviewing materials related to Raoultella spp. we noted many of the same materials referenced by De Jong et al. [1]. Additionally we noted several other reported cases of bacteremia due to Raoultella spp. These are summarized in Table I [2 – 5]. As described by De Jong et al. [1], many of these cases are associated with biliary disease. Also striking to us is the possible association with malignant processes that may have involvement of the biliary and/ or pancreatic system. Bile acids have previously been shown to be tumor promoters, and increased ornithine decarboxylase activity has been noted with rapid cell proliferation [6]. The importance of the biliary system and any impact of neoplastic processes on that system and its suitability as a milieu for growth of Raoultella spp. remain to be seen.
Background: The genotypes of Mycobacterium tuberculosis (MTB) have been found to be related to the risk of transmission and the development of drug resistance of this pathogen. Thus, exploring the molecular characteristics of MTB is helpful for understanding and controlling the spread of strains in areas with a high incidence of tuberculosis. Methods: We recruited 512 sputum smear-positive tuberculosis patients from 30 counties from 1 April to 30 June 2010; 503 MTB strains were isolated and 497 were successfully genotyped. We genotyped the strains based on a new 15-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) method in combination with spacer-oligonucleotide typing (spoligotyping) technology. Results: Based on spoligotyping, 487 strains displayed known patterns, and 10 were absent from the current global spoligotyping database (SpolDB4). The predominant spoligotypes belonged to the Beijing or Beijing-like family (81.1%). When we used the new 15-locus (MIRU-15) set for the MIRU-VNTR analysis, 388 different patterns were identified, including 46 clusters and 342 unique patterns. The combination of spoligotyping and MIRU-15 demonstrated a high discriminatory power. The proportion of clusters varied significantly between the Beijing and non-Beijing family strains, but no significant association was observed between multidrug resistance and Beijing family strains. Conclusions: The present study demonstrated that the Beijing family strains are the most prevalent in rural China. Spoligotyping in combination with the new MIRU-15 technique is useful for the epidemiological analysis of MTB transmission and could be used as a first-line method for the large-scale genotyping of MTB.
Background: Daily chlorhexidine (CHG) bathing has been used as a precaution to reduce the rate of healthcare-associated bloodstream infections (HA-BSI). The application frequency of CHG bathing remains unclear, this procedure has been implemented daily by this time. The aim of this study was to determine the efficacy of weekly whole-body douche with CHG shower gel on rates of HA-BSI. Methods: We conducted a prospective intervention trial in medical, surgical, and anesthesiology intensive care units (ICUs) in a tertiary teaching hospital from June 2011 to November 2012. This study included three periods. During the first period, patients received a daily bed bath by wiping with water and soap. In the second period patients were given a weekly douche with water and soap; in the third period patients were given a weekly douche with CHG shower gel. The rates of HA-BSI were compared between the three periods using Poisson regression analysis. Results: The central line-associated bloodstream infection rates did not decline significantly between periods (p = 0.76). The laboratory-confirmed bloodstream infection (LCBSI) rates in the first, second, and third periods were 7.1, 4, and 1.7, respectively. The LCBSI rates were reduced 43.7% from the first period to the second period (p = 0.03). In addition, there was a 57.5% reduction in LCBSI rates between the second and third periods (p < 0.001). Interestingly, the major decline (76.1%) was determined from the first to the third period (p < 0.002). Conclusions: Weekly douche with CHG shower gel significantly reduced LCBSI rates. Further studies are needed to validate the clinical impact of different intervals of CHG bathing.
Objectives: The varicella vaccine is an effective post-exposure prophylaxis (PEP) for chickenpox. This study aimed to analyze the cost-effectiveness of PEP using varicella vaccine for pediatric patients from the perspective of the public healthcare provider in Hong Kong. Methods: A decision tree was designed to compare cost and clinical outcomes of PEP with varicella vaccine versus no PEP in pediatric patients (aged 1-18 y) susceptible to chickenpox with household exposure. Two tiers of outcome were simulated: (1) total direct medical cost per subject exposed, and (2) the quality-adjusted life-year (QALY) loss associated with chickenpox per subject exposed. Model inputs were retrieved from local epidemiology and the medical literature. A sensitivity analysis was performed on all parameters to test the robustness of model results. Results: The base-case analysis showed PEP with varicella vaccine to be less costly (expected cost USD 320 vs USD 731) with lower QALY loss (0.00423 QALY vs 0.01122 QALY) when compared to no PEP. The sensitivity analysis showed that PEP with varicella vaccine was less costly if PEP effectiveness was >6.2% or the chickenpox infection rate without PEP was >8.6%. In 10,000 Monte Carlo simulations, PEP with vaccine was cost-effective over 99% of the time, with a mean cost saving of USD 611 per patient (95% confidence interval USD 602-620; p < 0.001) and lower mean QALY loss of 0.00809 QALY (95% confidence interval 0.00802-0.00816 QALY; p < 0.001). Conclusions: Using varicella vaccine as PEP appears to be a cost-saving strategy to avert QALY loss in susceptible pediatric patients exposed to chickenpox in Hong Kong.
Pneumocystis jirovecii pneumonia (PCP) is emerging in HIV-negative patients, for whom the prognosis is significantly worse than in HIV-infected patients and risk factors are poorly characterized. We performed an observational, multicentre, prospective study of 56 consecutive cases of documented PCP in HIV-negative patients, and found that: (1) the main underlying conditions were haematological malignancies (43%), solid tumours (25%), inflammatory diseases (20%), and solid organ transplantation (7%); (2) most patients (80%) had received prolonged corticosteroids, with a mean daily dose of 47.3 +/- 32.8 mg equivalent prednisone when PCP was diagnosed, and a mean cumulative dose of 5807 +/- 5048 mg over the last 12 months; and (3) the median CD4 cell count was 0.12 x 10(9)/l (range 0.0-1.42), with a median CD4/CD8 ratio of 1.32 (0.0-6.4). These findings may be used to better target PCP prophylaxis according to the level of risk and contribute to decrease the burden of PCP in HIV-negative patients.
BACKGROUND:Extended-spectrum beta-lactamase (ESBL)-producing bacteria are an escalating problem threatening health. Devastating consequences can result in neonatal intensive care units (NICU) due to these bacteria. The aim of this study was to investigate the efficacy of once-a-week screening (July 2010 to September 2012) versus screening on demand (April 2008 to June 2010).MATERIALS AND METHODS:The investigation was an open retrospective descriptive study comparing 2 unpaired groups, the first exposed to screening on demand and the second to screening once a week. All other infection control measures were unchanged. Both groups were cared for in the NICU of Skåne University Hospital. Parameters compared were the proportion of cultured neonates, prevalence, time before detection, number of secondary cases, and clinical infections due to ESBL-producing bacteria.RESULTS:The proportion of cultured neonates increased from 28% to 49% (p < 0.05) in period 2. The time from admission to detection was 8 days shorter in period 2 (p < 0.05). Secondary cases decreased from 44% to 9% (p < 0.05), and clinical infections from 4 to 0 cases (p < 0.05). During period 2, the prevalence of colonization was 1.77%.CONCLUSIONS:Once-a-week screening is a strategy to control the epidemiology of unwanted pathogens among newborn infants. It provides the opportunity for early intervention, thereby avoiding secondary cases and infections. Premature neonates in particular benefit from this approach. The prevalence of ESBL of 1.77% is low from an international perspective. ESBL appear to be introduced onto the ward by mothers colonized with ESBL.
Background: In recent years, the clinical use of interferon gamma release assays (IGRAs) has increased exponentially, while their indications remain controversial given difficulties in interpretation. Four indications were recommended by the French National Authority for Health (HAS) in 2006. We evaluated the utilization of the QuantiFERON-TB Gold In-Tube (QFT-IT) test over a 1-y period in a French university hospital and the impact of IGRA results in particular. Methods: The QFT-IT tests requested in 2009 were analysed retrospectively, excluding those from the Occupational Health Department, the Regional Tuberculosis Centre, and rheumatology consultations for which the indications were clearly defined. Results: Three hundred and sixty QFT-IT tests were analysed. The interpretation was frequently problematic given the inclusion of a significant proportion of patients over 80 y of age (11%), immunocompromised patients (43%), and patients with a known history of tuberculosis (6%). The indications failed to comply with HAS recommendations in 42% of cases (151/360), i.e. 14% of all QFT-IT tests in 2009. Thirty-seven percent of request forms were related to suspected pulmonary tuberculosis. In the case of a positive QFT-IT test, the clinical decision-making was changed in 58% of cases when the indications met the HAS recommendations, compared with only 16% if they did not (p < 0.005). Conclusion: When the indications do not meet the health authority recommendations, the diagnostic value of the IGRA remains limited.
Abstract The T-SPOT.TB test (TS.TB), an interferon-gamma (IFN-γ) release assay (IGRA), is superior in diagnosing latent tuberculosis infection compared with the conventional tuberculin skin test (TST). However, whether cytotoxic chemotherapy and treatment with new-generation antineoplastic monoclonal antibodies affects the TS.TB is not certain. We evaluated the feasibility of using the TS.TB in this population. Sixteen cancer patients at high risk for tuberculosis exposure were prospectively evaluated with the TST and TS.TB. Blood samples were obtained 7.5 ± 89.3 days after the most recent cycle of antineoplastic therapy. Six patients (38%) were febrile within 24 h of blood sampling; high-dose corticosteroid therapy and profound treatment-induced neutropenia were present in 1 patient each. In all patients, TS.TB showed no evidence of latent tuberculosis infection. A robust mitogen-induced IFN-γ response was seen in samples from 14 patients (88%) despite therapy with high-dose corticosteroids, cyclophosphamide, fludarabine, gemtuzumab ozogamicin, and alemtuzumab. The presence of fever or profound neutropenia did not negatively impact mitogen response by peripheral lymphocytes. The 2 patients whose peripheral blood lymphocytes (> 500 cells/ml) failed to generate a cytokine response to ex vivo mitogen stimulation had refractory advanced cancer. Unlike the TST, a negative TS.TB provided interpretable results even in cancer patients undergoing new-generation immunosuppressive therapy.
Hepatitis E virus (HEV) is the most important causative agent of acute hepatitis in developing countries. The disease is usually characterized by a self-limiting, benign course. However, when particular conditions coexist (pregnancy, old age, pre-existing liver disease) it may run an unfavourable course. To date, 4 HEV genotypes have been described. Historically, in the Western world, HEV infection was considered a travel-related disease, however in the last 2 decades a great number of non-travel-related autochthonous cases have been described, more often related to genotype 3 or 4 and in the context of zoonosis. We report the case of an elderly Italian man with an acute fulminant HEV infection genotype 3e that developed in the context of pre-existing liver disease; this is the first case of an unfavourable outcome associated with subgenotype 3e. The potential pathogenicity of this subgenotype together with the influence of host-related risk factors are discussed.
Background: Procalcitonin (PCT) levels can be used to predict bacteremia and DNAemia in patients with sepsis. In this study, the diagnostic accuracy of PCT in predicting blood culture (BC) results and DNAemia, as detected by real-time PCR (RT-PCR), was compared with that of other markers of inflammation commonly evaluated in patients with suspected sepsis, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count. Methods: A total of 571 patients for whom BC, blood RT-PCR, PCT, CRP, ESR, and WBC count were requested for laboratory diagnosis of sepsis were included in the study. Receiver operating characteristic curve analysis was performed to compare the ability of the above biomarkers to predict BC and blood RT-PCR results. Results: A total of 108 pathogens were identified by BC (79 pathogens, 14.5% positive rate) and/or RT-PCR (90 pathogens, 16.5% positive rate), after exclusion of 26 contaminated samples. The PCT areas under the curve (AUCs) in predicting BC (0.843; 95% CI 0.796-0.890; p < 0.0001) and RT-PCR (0.916; 95% CI 0.888-0.945; p < 0.0001) results were significantly greater than AUCs found for CRP, ESR, and WBC count. Conclusions: PCT showed a better diagnostic accuracy than CRP, ESR, and WBC count in predicting DNAemia and bacteremia in patients with suspected sepsis.
In August 2012, 2 carbapenem-resistant Klebsiella pneumoniae isolates from the University of Szeged were submitted to the National Reference Laboratory at the National Centre for Epidemiology to confirm the carbapenem resistance mechanism. PCR assays and sequencing revealed that the isolates harboured the blaOXA-162 carbapenemase gene, a very recently described variant of OXA-48, and the blaCTX-M-15 extended-spectrum β-lactamase gene. The isolates had indistinguishable PFGE patterns and belonged to sequence type ST15. To the best of our knowledge, this is the first description of OXA-48-like carbapenemase-producing bacteria in Hungary and of an OXA-162-type carbapenemase gene in the K. pneumoniae ST15 clone.
Background: The incidence of invasive pneumococcal disease (IPD) appears to be associated with influenza. The objectives of this study were to evaluate the changes in IPD incidence and clinical data as well as the trends in Streptococcus pneumoniae serotype distribution in adults during the peak period of the 2009 influenza A H1N1 pandemic (IAP). Methods: We performed a prospective multicentre study on IPD from week 42 to 48, 2009 in an area of Barcelona (Catalonia, Spain) covering 1,483,781 adult inhabitants. Serotyping was done by Quellung reaction. The data from 2009 were compared to those from the same periods in 2008 and 2010. Results: Two hundred and three cases of IPD were detected during 2009, compared with 182 in 2008 and 139 in 2010. The incidence of IPD during the 7-week study period in 2009 (2.89) was statistically higher than that observed in 2008 (1.96) and 2010 (1.46). IAP was confirmed in 3/30 patients during the 2009 study period. Patients with IPD in 2009 were significantly healthier and younger than those in the other years, although the mortality was higher than in 2008 (p = 0.05) and 2010 (p > 0.05). Eleven (10 non-PCV-7) serotypes not present in 2008 appeared in 2009. Conclusions: During weeks 42 to 48, in which the 2009 IAP peaked in Catalonia, the incidence of IPD was statistically higher than that observed in the same time period in 2008 and 2010, with some differences in the epidemiological data, showing a close relationship between S. pneumoniae and influenza.
BACKGROUND:The clinical picture of ventilator-associated pneumonia (VAP) can be mimicked by other infectious and non-infectious diseases. The aim of this study was to determine the alternative diagnoses and to develop a diagnostic flow chart for patients suspected of having VAP not meeting the diagnostic broncho-alveolar lavage (BAL) criteria. METHODS:Adult intensive care patients with a clinical suspicion of VAP and negative BAL results were included. The clinical suspicion of VAP was based on the combination of clinical, radiological, and microbiological criteria. BAL was considered positive if cell differentiation revealed ≥ 2% cells with intracellular organisms and/or quantitative culture results of ≥ 10(4) cfu/ml. The most likely alternative diagnosis of fever and pulmonary densities was retrospectively determined by two authors independently. RESULTS:In all, 110 of 207 patients with suspected VAP did not meet the diagnostic BAL criteria and required further diagnostic evaluation. In 67 patients an alternative diagnosis for fever could be found. In 51 patients an alternative diagnosis of both fever and pulmonary densities could be established. In almost 40% of patients no alternative diagnosis could be provided. Non-bacterial pneumonia was diagnosed in 10 patients with Herpes simplex virus 1 (HSV-1) as the most common pathogen. In eight patients non-infectious pneumonitis was diagnosed. CONCLUSION:Due to the wide range of alternative diagnoses and applied tests the diagnostic work-up proved to be necessarily individualized and guided by repeated clinical assessment. The most frequently found alternative diagnoses were viral pneumonia and non-infectious pneumonitis.
Prophylaxis and treatment with antiretroviral drugs and elective caesarean section delivery have resulted in very low mother-to-child transmission of HIV during recent years. Updated general treatment guidelines and increasing knowledge about mother-to-child transmission have necessitated regular revisions of the recommendations for the prophylaxis and treatment of HIV-1 infection in pregnancy. The Swedish Reference Group for Antiviral Therapy (RAV) updated the recommendations from 2010 at an expert meeting on 11 September 2013. The most important revisions are the following: (1) ongoing efficient treatment at confirmed pregnancy may, with a few exceptions, be continued; (2) if treatment is initiated during pregnancy, the recommended first-line therapy is essentially the same as for non-pregnant women; (3) raltegravir may be added to achieve rapid reduction in HIV RNA; (4) vaginal delivery is recommended if at > 34 gestational weeks and HIV RNA is < 50 copies/ml and no obstetric contraindications exist; (5) if HIV RNA is < 50 copies/ml and delivery is at > 34 gestational weeks, intravenous zidovudine is not recommended regardless of the delivery mode; (6) if HIV RNA is > 50 copies/ml close to delivery, it is recommended that the mother should undergo a planned caesarean section, intravenous zidovudine, and oral nevirapine, and the infant should receive single-dose nevirapine at 48-72 h of age and post-exposure prophylaxis with 2 drugs; (7) if delivery is preterm at < 34 gestational weeks, a caesarean section delivery should if possible be performed, with intravenous zidovudine and oral nevirapine given to the mother, and single-dose nevirapine given to the infant at 48-72 h of age, as well as post-exposure prophylaxis with 2 additional drugs.
We present a case of amoebic colitis, misdiagnosed as inflammatory bowel disease and treated with corticosteroids, leading to severe necrotizing enterocolitis. We review the literature on the epidemiology, pathogenesis, diagnosis, and treatment of amoebic dysentery, with special emphasis on the association between immunosuppressive treatment and the development of severe invasive amoebiasis.
