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1.  The relationship between hand hygiene and health care-associated infection: it’s complicated 
The reasoning that improved hand hygiene compliance contributes to the prevention of health care-associated infections is widely accepted. It is also accepted that high hand hygiene alone cannot impact formidable risk factors, such as older age, immunosuppression, admission to the intensive care unit, longer length of stay, and indwelling devices. When hand hygiene interventions are concurrently undertaken with other routine or special preventive strategies, there is a potential for these concurrent strategies to confound the effect of the hand hygiene program. The result may be an overestimation of the hand hygiene intervention unless the design of the intervention or analysis controls the effect of the potential confounders. Other epidemiologic principles that may also impact the result of a hand hygiene program include failure to consider measurement error of the content of the hand hygiene program and the measurement error of compliance. Some epidemiological errors in hand hygiene programs aimed at reducing health care-associated infections are inherent and not easily controlled. Nevertheless, the inadvertent omission by authors to report these common epidemiological errors, including concurrent infection prevention strategies, suggests to readers that the effect of hand hygiene is greater than the sum of all infection prevention strategies. Worse still, this omission does not assist evidence-based practice.
PMCID: PMC4319644
compliance; epidemiological principles; study design; bacteria; control; multiple drug resistance
2.  Wide dissemination of extended-spectrum β-lactamase-producing Escherichia coli in community residents in the Indochinese peninsula 
Recent studies have reported a widespread distribution of extended-spectrum β-lactamase (ESBL)-producing bacteria, not only in the nosocomial setting, but also in the community; some local communities in Southeast Asia have been reported to show a high prevalence of ESBL-producing bacteria. However, the details regarding the quantitative/qualitative state of ESBL-producing bacterial spread in Southeast Asia are currently unclear. Thus, the aim of this study was to assess the state of ESBL-producing bacterial spread in community residents from the Indochinese peninsula, as a representative region of Southeast Asia. In order to achieve this aim, local community residents in Laos and Vietnam were examined for fecal carriage of ESBL-producing Enterobacteriaceae, and the findings were compared with data from a previous study in Thailand which was conducted in the same manner as this study. Between 47.0%–70.2% of the Laotian and Vietnamese residents carried ESBL-producing CTX-M genotype Enterobacteriaceae. The most common sub-genotypes of CTX-M were CTX-M-1 (33.0%–47.5%) and CTX-M-9 (47.5%–64.1%), and these rates were similar among all three countries. Taken together, these results confirmed that ESBL-producing Enterobacteriaceae are widely disseminated in Indochinese countries, such as Thailand, Laos, and Vietnam.
PMCID: PMC4315533
extended-spectrum β-lactamase (ESBL); rural residents; Indochinese peninsula; fecal carriage
3.  Antibiotic lock therapy: review of technique and logistical challenges 
Antibiotic lock therapy (ALT) for the prevention and treatment of catheter-related bloodstream infections is a simple strategy in theory, yet its real-world application may be delayed or avoided due to technical questions and/or logistical challenges. This review focuses on these latter aspects of ALT, including preparation information for a variety of antibiotic lock solutions (ie, aminoglycosides, beta-lactams, fluoroquinolones, folate antagonists, glycopeptides, glycylcyclines, lipopeptides, oxazolidinones, polymyxins, and tetracyclines) and common clinical issues surrounding ALT administration. Detailed data regarding concentrations, additives, stability/compatibility, and dwell times are summarized. Logistical challenges such as lock preparation procedures, use of additives (eg, heparin, citrate, or ethylenediaminetetraacetic acid), timing of initiation and therapy duration, optimal dwell time and catheter accessibility, and risks of ALT are also described. Development of local protocols is recommended in order to avoid these potential barriers and encourage utilization of ALT where appropriate.
PMCID: PMC4271721  PMID: 25548523
antibiotic lock; biofilm; bacteremia; catheter-related bloodstream infection
4.  Current perspectives on the spread of dengue in India 
Dengue fever (DF) and dengue hemorrhagic fever (DHF) are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with DHF, mainly in Southeast Asia. Dengue in India has dramatically expanded over the last few decades, with rapidly changing epidemiology. The first major DHF outbreak in the entire nation occurred in 1996 by dengue virus serotype 2, and after a gap of almost a decade, the country faced yet another DF outbreak in the year 2003 by dengue virus serotype 3. A dramatic increase in the number and frequency of outbreaks followed, and, at present, in most of the states of India, dengue is almost endemic. At present, all the four serotypes are seen in circulation, but the predominant serotype keeps changing. Despite this trend, surveillance, reporting, and diagnosis of dengue remain largely passive in India. More active community-based epidemiological studies with intensive vector control and initiatives for dengue vaccine development should be geared up to control the spread of dengue in India. We review here the factors that may have contributed to the changing epidemiology of dengue in India.
PMCID: PMC4266245  PMID: 25525374
dengue; epidemiology; India; pathogenesis; vaccine
5.  The effect of a unique propolis compound (Propoelix™) on clinical outcomes in patients with dengue hemorrhagic fever 
Dengue fever is a mosquito-borne virus belonging to the family Flaviviridae. It is an old virus that has re-emerged globally over the past 20 years and now causes a global burden of 50 million infections per year across approximately 100 countries. Despite this, there is no safe vaccine available, and therapy is largely supportive. Its pathogenesis is multifaceted and currently still poorly understood, leading to a lack of disease-specific therapy. Propolis is a natural antiviral and anti-inflammatory product derived from the saps of plants and mixed with the saliva of honeybees. Propoelix™ is a uniquely potent and water-soluble extract of propolis containing high concentrations of anti-inflammatory compounds like caffeic acid phenethyl ester.
The primary objective is to determine the effectiveness of a unique propolis extract (Propoelix™) on the clinical course of patients with dengue hemorrhagic fever (DHF). The secondary objective is to examine the effect of Propoelix™ on tumor necrosis factor-α (TNF-α) levels in patients with DHF.
A double-blind, randomized, placebo-controlled trial was conducted at the Department of Internal Medicine, Gatot Soebroto Central Army Hospital in Jakarta, Indonesia, from May 2012 to July 2013. Sixty-three patients who met the inclusion criteria were enrolled in the trial. Patients were randomized to receive either two capsules of Propoelix™ 200 mg three times a day or placebo daily for 7 days. Clinical and laboratory variables of both groups, including the anti-inflammatory marker TNF-α, were investigated. Patients were deemed technically fit for discharge if their platelet counts had recovered and exceeded 100,000/μL but were all observed as inpatients for 7 days.
There were 31 patients in the Propoelix™ treatment group and 32 patients in the placebo group. Platelet counts in the Propoelix™-treated group showed a trend toward a faster recovery by day 3 of admission and became statistically significant by day 6 (101.42±48.79 vs 80.78±43.35 [103/mL], P=0.042) and day 7 (146.67±64.68 vs 107.84±57.22 [103/mL], P=0.006). Patients treated with Propoelix™ had a significantly greater decline in TNF-α levels on day 7 of therapy compared with patients in the placebo group (P=0.018). They also had a significantly shorter length of hospitalization compared with those in the placebo group (4.69±0.78 days vs 5.46±1.16 days, P=0.012).
Propoelix™ appears to hasten the improvement in platelet counts and TNF-α levels and shortens the duration of hospitalization in patients with DHF.
PMCID: PMC4266269  PMID: 25525372
effectiveness; Propoelix™; DHF
6.  Does antimicrobial use density at the ward level influence monthly central line-associated bloodstream infection rates? 
The aim of this study was to elucidate risk factors, including ward antimicrobial use density (AUD), for central line-associated bloodstream infection (CLABSI) as defined by the Centers for Disease Control and Prevention in a 430-bed community hospital using central venous lines with closed-hub systems. We calculated AUD as (total dose)/(defined daily dose × patient days) ×1,000 for a total of 20 drugs, nine wards, and 24 months. Into each line day data, we inputed AUD and device utilization ratios, number of central line days, and CLABSI. The ratio of susceptible strains in isolates were subjected to correlation analysis with AUD. Of a total of 9,997 line days over 24 months, CLABSI was present in 33 cases (3.3 ‰), 14 (42.4%) of which were on surgical wards out of nine wards. Of a total of 43 strains isolated, eight (18.6%) were methicillin-resistant Staphylococcus aureus (MRSA); none of the MRSA-positive patients had received cefotiam before the onset of infection. Receiver-operating characteristic analysis showed that central line day 7 had the highest accuracy. Logistic regression analysis showed the central line day showed an odds ratio of 5.511 with a 95% confidence interval of 1.936–15.690 as did AUD of cefotiam showing an odds ratio of 0.220 with 95% confidence interval of 0.00527–0.922 (P=0.038). Susceptible strains ratio and AUD showed a negative correlation (R2=0.1897). Thus, CLABSI could be prevented by making the number of central line days as short as possible. The preventative role of AUD remains to be investigated.
PMCID: PMC4266251  PMID: 25525373
bloodstream infection; central line; antimicrobial use density
7.  Virulence and antimicrobial resistance of Escherichia coli isolated from Tigris River and children diarrhea 
To investigate the virulence factors including hemolysin production, β-lactamase production, and biofilm formation. Antimicrobial resistance and plasmid content of 20 Escherichia coli isolates obtained from feces and Tigris water were screened.
Ten clinical and ten environmental E. coli isolates were collected from children diarrhea and swim areas on Tigris River in Baghdad city, Iraq, respectively. The bacterial isolates were identified by cultural characteristics, Gram stain, biochemical tests, and screened for the presence of E. coli O157:H7 serotype. Bacterial E. coli isolates were investigated for hemolysin production, biofilm formation, and β-lactamase production. Antibiotics susceptibility and plasmid content were determined.
A total of ten clinical and ten water E. coli isolates were studied. Results showed that all E. coli isolates give negative results for latex O157:H7. Virulence factors analysis showed that 6/10 water isolates and 2/10 clinical isolates were hemolytic, 5/10 water isolates and 3/10 clinical isolates were biofilm formation, and 7/10 water isolates and 4/10 clinical isolates were β-lactamase producer. Antibiotics profile showed that all bacterial isolates were multidrug resistant. All E. coli isolates (100%) were resistant to carbenicillin, cefodizime, imipenem, and piperacillin. The plasmid DNA analysis showed that all E. coli isolates contained plasmid with molecular weight range between 4.507 kbp and 5.07 kbp, but clinical isolates contained multiple small and mega plasmids.
Our study revealed that E. coli isolates from river water exhibit a higher level of hemolysin production, β-lactamase production, and biofilm formation than feces isolates may be due to long adaptation. On the other hand, clinical E. coli isolates from feces showed higher level of antibiotic resistance and have multiple plasmids.
PMCID: PMC4251758  PMID: 25473302
E. coli; hemolysin; β-lactamase; biofilm; multidrug resistance; plasmid
8.  Genetic relatedness and host specificity of Pseudomonas aeruginosa isolates from cystic fibrosis and non-cystic fibrosis patients 
Pseudomonas aeruginosa is one of the primary pathogens isolated more frequently in cystic fibrosis (CF) and it exhibits innate resistance to a wide range of antibiotics.
We sought to determine whether the highly prevalent genotypes of P. aeruginosa are specifically linked to CF patients and have any related multidrug antibiotic resistance. Isolates from hospitalized non-CF patients and from environmental sources were also genotypically analyzed.
Collections of P. aeruginosa from lower respiratory secretions (n=45) were genotyped using pulsed-field gel electrophoresis (PFGE). Phenotypic screening for antibiotic susceptibility was performed for the common antimicrobial agents by E-test and automated Phoenix method.
P. aeruginosa isolates from CF (n=32), hospitalized non-CF patients (n=13), and environment sources (n=5) were analyzed. The population structure of P. aeruginosa is highly diverse and population-specific. All PFGE results of P. aeruginosa isolates fall among four major clusters. Cluster 1 contained 16 P. aeruginosa isolates from CF patients and two from environmental sources; cluster 2 contained 11 P. aeruginosa isolates from CF and one each from non-CF and environmental sources; cluster 3 contained 12 P. aeruginosa isolates from hospitalized non-CF patients and two P. aeruginosa isolates from one CF patient and one environmental source; and cluster 4 consisted of three isolates from CF patients and one from the environment. The majority of multidrug-resistant P. aeruginosa isolates were in clusters 3 and 4. P. aeruginosa isolates from CF patients were resistant to ciprofloxacin (34.4%) followed by resistance to amikacin and gentamicin (each 28%), whereas the majority of isolates from non-CF patients were resistant to meropenem (69%) and were grouped in cluster 3.
PFGE of P. aeruginosa isolates from CF patients shows a high degree of similarity, suggesting specific adaptation of these clones to CF-affected lungs. The hospitalized non-CF cluster has a different clonal origin, indicating specific clustering in a specific location, suggesting hospital-acquired P. aeruginosa infections.
PMCID: PMC4242404  PMID: 25429232
cystic fibrosis; drug susceptibility testing; Pseudomonas aeruginosa; pulsed-field gel electrophoresis
9.  Nosocomial bacteriuria in elderly inpatients may be leading to considerable antibiotic overuse: an audit of current management practice in a secondary level care hospital in New Zealand 
Bacteriuria in the form of symptomatic urinary tract infection (UTI) and asymptomatic bacteriuria (ASB) is common in the elderly. There is no clinical benefit obtained by treating elderly individuals with ASB. However, its high prevalence leads to the overdiagnosis of UTI and unnecessary antibiotic use, which can result in adverse events, including Clostridium difficile diarrhea and reinfection with antibiotic-resistant organisms.
This was a retrospective audit that assessed the management of nosocomial bacteriuria in elderly patients admitted to the over-65 years rehabilitation unit of a secondary level care hospital in New Zealand. Identified bacteriuria episodes had the timing of sample collection relative to admission, microbial etiology, antibiotic susceptibility profile, inflammatory marker level, and treatment determined. Episodes were classified into six different clinical groups based on the presence or absence of signs and symptoms, urinary catheter status, and systemic inflammatory response. The proportion of bacteriuria episodes by clinical grouping and the level of treatment by clinical group were determined, followed by assessment of the amount of overtreatment in terms of the number of unnecessary antibiotic courses and unnecessary antibiotic treatment days.
Significant bacteriuria was identified in 30% of patients, with 35% of urine samples collected in the immediate postadmission period. Fifty-four percent of the bacteriuria episodes were ASB or catheter-associated ASB (CA-ASB) without an inflammatory response, 24% were ASB or CA-ASB with raised inflammatory markers, and 22% were UTI or CA-UTI. The most common cause of bacteriuria was Escherichia coli, although the etiology was diverse, especially after prolonged hospitalization or in catheterized patients. A large proportion of organisms were resistant to one or more of the commonly used oral antibiotics. Treatment of ASB and CA-ASB accounted for 43% of all antibiotic courses received. Furthermore, treatment of ASB and CA-ASB combined with unnecessarily prolonged treatment days for clinically relevant infections accounted for 55% of all antibiotic treatment days received.
The results suggest that inappropriate urine screening was occurring and that 43% of antibiotic courses and 55% of all antibiotic treatment days were unnecessary. Current practice is amenable to improvement by performing urine culture only when clinically indicated, focusing on clinical signs and symptoms to diagnose clinically significant UTI rather than a positive culture, and using, where possible, the ecologically least damaging antibiotic for the shortest duration required.
PMCID: PMC4235501  PMID: 25419149
asymptomatic bacteriuria; nosocomial urinary tract infection; elderly; antibiotic overuse
10.  Bacterial bloodstream infections and antimicrobial susceptibility pattern in pediatric hematology/oncology patients after anticancer chemotherapy 
Bloodstream infections in pediatric hematology and oncology represent a major problem worldwide, but this has not been studied in Qatar. In this study, we investigated the burden of infection and the resistance pattern in the bacterial etiology, in the only tertiary pediatric hematology and oncology center in Qatar.
All pediatric cancer patients (n=185) were evaluated retrospectively during the period 2004–2011; a total of 70 (38%) patients were diagnosed with bloodstream infections. Bacterial etiology was determined, along with their susceptibility patterns. Neutropenia, duration of neutropenia, fever, duration of fever, and C-reactive protein (CRP) were evaluated throughout the study.
A total of 70 patients (38%) were diagnosed with acute leukemias, lymphomas, solid tumors, or brain tumors; those patients experienced 111 episodes of bacteremia. The most common Gram-positive (n=64 [55%]) isolates were Staphylococcus epidermidis (n=26), Staphylococcus hominis (n=9), and Staphylococcus haemolyticus (n=7), and the common Gram-negative (n=52 [45%]) isolates were Klebsiella pneumoniae (n=14), Pseudomonas aeruginosa (n=10), and Escherichia coli (n=7). There was a significant association observed between fever with positive blood culture and different types of cancer (P=0.035). The majority of bacteremia (n=68 [61.3%]) occurred in nonneutropenic episodes. Elevated values of CRP (≥5 mg/L) were detected in 82 (95.3%) episodes and were negatively correlated with absolute neutrophil count (ANC) (r=−0.18; P=0.248) among all cases. However, the infection-related fatality rate was 2.2% (n=4), with three caused by Gram-negative pathogens. Multidrug resistant organisms were implicated in 33 (28.4%) cases and caused three of the mortality cases.
Multidrug resistant organisms cause mortality in pediatric cancer patients. Investigation of antimicrobial susceptibility of these organisms may guide successful antimicrobial therapy and improve the surveillance and quality of pediatric malignancy care.
PMCID: PMC4226521  PMID: 25395866
risk factors; antibiotic susceptibility
11.  Middle East respiratory syndrome coronavirus: epidemiology and disease control measures 
The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in 2012 resulted in an increased concern of the spread of the infection globally. MERS-CoV infection had previously caused multiple health-care-associated outbreaks and resulted in transmission of the virus within families. Community onset MERS-CoV cases continue to occur. Dromedary camels are currently the most likely animal to be linked to human MERS-CoV cases. Serologic tests showed significant infection in adult camels compared to juvenile camels. The control of MERS-CoV infection relies on prompt identification of cases within health care facilities, with institutions applying appropriate infection control measures. In addition, determining the exact route of transmission from camels to humans would further add to the control measures of MERS-CoV infection.
PMCID: PMC4226520  PMID: 25395865
MERS; Middle East respiratory syndrome coronavirus; epidemiology; control measures; transmission; Saudi Arabia
12.  An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany 
Across Europe, methicillin-resistant Staphylococcus aureus (MRSA) is considered to be the primary cause of nosocomial pneumonia (NP). In Germany alone, approximately 14,000 cases of MRSA-associated NP occur annually, which may have a significant impact on health care resource use and associated economic costs. The objective of this study was to investigate the economic impact of linezolid compared with that of vancomycin in the treatment of hospitalized patients with MRSA-confirmed NP in the German health care system.
A 4-week decision tree model incorporated published data and expert opinion on clinical parameters, resource use, and costs (2012 euros) was constructed. The base case first-line treatment duration for patients with MRSA-confirmed NP was 10 days. Treatment success (survival), failure due to lack of efficacy, serious adverse events, and mortality were possible outcomes that could impact costs. Alternate scenarios were analyzed, such as varying treatment duration (7 or 14 days) or treatment switch due to a serious adverse event/treatment failure (at day 5 or 10).
The model calculated total base case inpatient costs of €15,116 for linezolid and €15,239 for vancomycin. The incremental cost-effectiveness ratio favored linezolid (versus vancomycin), with marginally lower costs (by €123) and greater efficacy (+2.7% absolute difference in the proportion of patients successfully treated for MRSA NP). Approximately 85%–87% of the total treatment costs were attributed to hospital stay (primarily in the intensive care unit). Sensitivity analysis yielded similar results.
The model results show that linezolid is a cost-effective alternative to vancomycin for MRSA-confirmed NP, largely attributable to the higher clinical response rate of patients treated with linezolid.
PMCID: PMC4216023  PMID: 25368526
cost-effectiveness; linezolid; vancomycin; nosocomial pneumonia; resistant; Staphylococcus aureus
13.  Optimizing antimicrobial therapy in critically ill patients 
Critically ill patients with infection in the intensive care unit (ICU) would certainly benefit from timely bacterial identification and effective antimicrobial treatment. Diagnostic techniques have clearly improved in the last years and allow earlier identification of bacterial strains in some cases, but these techniques are still quite expensive and not readily available in all institutions. Moreover, the ever increasing rates of resistance to antimicrobials, especially in Gram-negative pathogens, are threatening the outcome for such patients because of the lack of effective medical treatment; ICU physicians are therefore resorting to combination therapies to overcome resistance, with the direct consequence of promoting further resistance. A more appropriate use of available antimicrobials in the ICU should be pursued, and adjustments in doses and dosing through pharmacokinetics and pharmacodynamics have recently shown promising results in improving outcomes and reducing antimicrobial resistance. The aim of multidisciplinary antimicrobial stewardship programs is to improve antimicrobial prescription, and in this review we analyze the available experiences of such programs carried out in ICUs, with emphasis on results, challenges, and pitfalls. Any effective intervention aimed at improving antibiotic usage in ICUs must be brought about at the present time; otherwise, we will face the challenge of intractable infections in critically ill patients in the near future.
PMCID: PMC4208492  PMID: 25349478
ICU; antimicrobial therapies; antimicrobial stewardship; pharmacokinetics; pharmacodynamics; antimicrobial resistance; early diagnosis
14.  Genotypes and phenotypes of Shiga toxin-producing Escherichia coli (STEC) in Abeokuta, Southwestern Nigeria 
To characterize the prevalence of hemolytic Shiga toxin-producing Escherichia coli (STEC) with a multidrug-resistant pattern in different age groups in Abeokuta, Nigeria.
Nonrepetitive E. coli isolates were collected from 202 subjects with or without evidence of diarrhea. Each isolate was biochemically identified and antimicrobial susceptibility testing was performed using the disk diffusion method. A sorbitol fermentation test of all the E. coli isolates was done and the minimum inhibitory concentration of suspected STEC was measured by the standard broth microdilution method to determine antibiotic resistance. The genotypes of stx1, stx2, and hlyA were determined by polymerase chain reaction assay.
The majority of subjects were aged ≥40 years (41.6%) and were female (61.9%). Of the 202 subjects, 86.1% had STEC isolates (P<0.05). A high rate of STEC isolates resistant to amoxicillin (90.6%), cefotaxime (77.7%), and cefuroxime (75.7%) was observed. Resistance to amoxicillin, gentamicin, and cefotaxime was demonstrated with a minimum inhibitory concentration >16 μg/mL in 13.9%, 11.4%, and 10.4% of the isolates, respectively. The prevalence of stx1, stx2, and hlyA was 13.9%, 6.9%, and 2.0%, respectively; 5.5% of stx1 were in the 0–10-year-old age group, 3.5% of stx2 were aged ≥40 and above, and 1.0% of the hlyA isolates were in the 0–10-year-old age group.
The prevalence of virulent STEC is a public health concern. The use of polymerase chain reaction assay should aid quick detection of this virulent serotype and help curb the severe epidemic of human diseases associated with STEC infections.
PMCID: PMC4206374  PMID: 25342913
STEC; resistance; stx1; stx2; hlyA; Nigeria
15.  Host–pathogen interactions and immune evasion strategies in Francisella tularensis pathogenicity 
Francisella tularensis is an intracellular Gram-negative bacterium that causes life-threatening tularemia. Although the prevalence of natural infection is low, F. tularensis remains a tier I priority pathogen due to its extreme virulence and ease of aerosol dissemination. F. tularensis can infect a host through multiple routes, including the intradermal and respiratory routes. Respiratory infection can result from a very small inoculum (ten organisms or fewer) and is the most lethal form of infection. Following infection, F. tularensis employs strategies for immune evasion that delay the immune response, permitting systemic distribution and induction of sepsis. In this review we summarize the current knowledge of F. tularensis in an immunological context, with emphasis on the host response and bacterial evasion of that response.
PMCID: PMC4173753  PMID: 25258544
LVS; Schu S4; tularemia; host immunity; Francisella tularensis
16.  Peptidomimetics as a new generation of antimicrobial agents: current progress 
Antibiotic resistance is an increasing public health concern around the world. Rapid increase in the emergence of multidrug-resistant bacteria has been the target of extensive research efforts to develop a novel class of antibiotics. Antimicrobial peptides (AMPs) are small cationic amphiphilic peptides, which play an important role in the defense against bacterial infections through disruption of their membranes. They have been regarded as a potential source of future antibiotics, owing to a remarkable set of advantageous properties such as broad-spectrum activity, and they do not readily induce drug-resistance. However, AMPs have some intrinsic drawbacks, such as susceptibility to enzymatic degradation, toxicity, and high production cost. Currently, a new class of AMPs termed “peptidomimetics” have been developed, which can mimic the bactericidal mechanism of AMPs, while being stable to enzymatic degradation and displaying potent activity against multidrug-resistant bacteria. This review will focus on current findings of antimicrobial peptidomimetics. The potential future directions in the development of more potent analogs of peptidomimetics as a new generation of antimicrobial agents are also presented.
PMCID: PMC4155802  PMID: 25210467
drug resistance; infection; antimicrobial peptides
17.  E. coli O157 outbreaks in the United Kingdom: past, present, and future 
This review describes Escherichia coli O157 outbreaks in the United Kingdom, beginning from the first, in the 1980s, to those recorded in 2013. We point out that the United Kingdom differs from other countries, particularly the United States, in that it has had a considerable number of outbreaks associated with butchers, but very few caused by contaminated burgers. Two of the butcher-associated outbreaks (in central Scotland in 1996 and South Wales in 2005) were very large and are considered here in detail; the reviewer conducted detailed investigations into both outbreaks. Also considered is the very large outbreak that occurred in visitors to an open farm in Surrey in 2009. Detailed descriptions of some milk-borne outbreaks and incidents connected with camping and childrens’ nurseries have been published, and these are also considered in this review. Large outbreaks in the United Kingdom have sometimes led to policy developments regarding food safety, and these are considered, together with public reactions to them, their health effect, and their value, as examples to follow or eschew in terms of the procedures to be adopted in response to incidents of this kind. Regulatory and legal consequences are also considered. As a wise man said, making predictions is difficult, particularly about the future. This review follows this position but points out that although human infections caused by E. coli O157 are rare in the United Kingdom, their incidence has not changed significantly in the last 17 years. This review points out that although a response to an outbreak is to say “lessons must be learned”, this response has been tempered by forgetfulness. Accordingly, this review restricts its recommendations regarding outbreaks to two: the crucial importance of a rapid response and the importance of experience, and even “gut feeling”, when an inspector is evaluating the safety of a food business.
PMCID: PMC4149388  PMID: 25187729
E. coli O157; outbreaks; UK
18.  Moxifloxacin resistance in the F15/LAM4/KZN extensively drug-resistant strain of Mycobacterium tuberculosis 
Moxifloxacin (MXF) has been advocated for the treatment of extensively drug-resistant (XDR) tuberculosis despite resistance to older-generation fluoroquinolones. We investigated the relationship between the minimum inhibitory concentration (MIC) of MXF and mutations in the gyrA and gyrB genes in Mycobacterium tuberculosis (MTB) isolates from KwaZulu-Natal (KZN) Province of South Africa.
Materials and methods
MICs of 56 MTB isolates were compared to the mutations in the quinolone resistance-determining region known to confer fluoroquinolone resistance. Isolates were genotyped by IS6110 restriction fragment length polymorphism analysis.
The circulating F15/LAM4/KZN XDR strain circulating in KZN Province harbored the A90V mutation and displayed high-level resistance with MICs of 8 mg/L for ciprofloxacin and ofloxacin and ≥1 mg/L for MXF.
The inclusion of MXF in XDR-TB treatment regimens requires careful consideration in our setting, where clinical outcome data in MXF-containing regimens are unavailable.
PMCID: PMC4149401  PMID: 25187730
fluoroquinolones; susceptibility testing; strain typing; drug-resistance
19.  Microbiology, resistance patterns, and risk factors of mortality in ventilator-associated bacterial pneumonia in a Northern Thai tertiary-care university based general surgical intensive care unit 
Ventilator-associated pneumonia (VAP) occurrence, causative pathogens, and resistance patterns in surgical intensive care units (SICU) are different between Western and developing Asian countries. In Thailand, resistant organisms have progressively increased in the last decade. However, the evidence describing causes of VAP and its outcomes, especially secondary to resistant pathogens, in Asian developing countries’ SICUs is very limited. Therefore, the objective of this study was to describe the incidence, pathogen characteristics, and risk factors that impact mortality and patient survival following VAP in a tertiary Northern Thai SICU.
Between 2008 and 2012, VAP occurred in a total of 150 patients in Chiang Mai University’s general SICUs (6.3±2.8 cases per 1,000 mechanical ventilator days). The following clinical data were collected from 46 patients who died and 104 patients who survived: microbiologic results, susceptible patterns, and survival status at hospital discharge. Antimicrobial susceptibility patterns were classified as susceptible, multidrug resistant (MDR), extensively drug resistant (XDR), and pan-drug resistant (PDR). The hazard ratio (HR) was calculated for risk factor analysis.
Regarding the microbiology, gram negative organisms were the major pathogens (n=142, 94.7%). The first three most common organisms were Acinetobacter baumannii (38.7% of all organisms, mortality 41.4%), Klebsiella pneumoniae (17.3%, mortality 30.8%), and Pseudomonas aeruginosa (16.7%, mortality 16%) respectively. The most common gram positive organism was Staphylococcus aureus (4.0%, mortality 50%). The median day of VAP occurrence were significantly different between the three groups (P<0.01): susceptible (day 4), MDR (day 5), and XDR (day 6.5). Only half of all VAP cases were caused by susceptible organisms. Antibiotic resistance was demonstrated by 49.3% of the gram negative organisms and 62.5% of the gram positive organisms. Extensive drug resistance was evident only in Acinetobacter baumannii (30.6%) and Pseudomonas aeruginosa (1.3%). No pan-drug resistance was found during surveillance. The significant HR risk factors were age (P=0.03), resistant organisms (P=0.04), XDR (P=0.02), and acute physiology and chronic health evaluation II score (<0.01). Acinetobacter baumannii (P=0.06) and intubation due to severe sepsis (P=0.08) demonstrated a trend toward a significant increase in the HR. On the other hand, there were significantly decreased HRs in trauma patients (P=0.01). Initial administration of appropriate antibiotic therapy had a tendency toward a significant decrease in the HR (P=0.08).
Gram negative organisms were the primary cause of bacterial VAP in Chiang Mai University’s general SICU. Resistant strains were present in half of all VAP cases and were associated with the day of VAP onset. Regarding risk factors, age, acute physiology, chronic health evaluation II score, resistant organisms (especially XDR), and being a non-trauma patient increased the risk of mortality.
PMCID: PMC4140702  PMID: 25152627
surgical intensive care unit; ventilator-associated pneumonia; device-related incidence rate; drug resistant organism; Acinetobacter baumannii
20.  Comparative analysis of the infectivity rate of both Borrelia burgdorferi and Anaplasma phagocytophilum in humans and dogs in a New Jersey community 
Ticks are important vectors of disease and transmit an extensive array of bacterial, viral and protozoan diseases to both humans and dogs within a community. Borrelia burgdorferi, the causative agent of Lyme disease, has been extensively studied within both the human and veterinary population. Anaplasma phagocytophilum, an intracellular rickettsial pathogen also transmitted by ixodid ticks, has emerged as an important zoonotic infection with significant veterinary and medical implications, and is responsible for both canine granulocytic anaplasmosis and human granulocytic anaplasmosis. Multiple surveys exist in the international literature referencing infectivity rates of both of these diseases separately in both the dog and human populations. This is the first study to simultaneously examine the infectivity rate of both anaplasmosis and Lyme disease in humans and dogs in a community endemic for tick-borne diseases.
PMCID: PMC4132225  PMID: 25143748
Lyme disease; anaplasmosis; dogs; humans
21.  Actinomycosis: etiology, clinical features, diagnosis, treatment, and management 
Actinomycosis is a rare chronic disease caused by Actinomyces spp., anaerobic Gram-positive bacteria that normally colonize the human mouth and digestive and genital tracts. Physicians must be aware of typical clinical presentations (such as cervicofacial actinomycosis following dental focus of infection, pelvic actinomycosis in women with an intrauterine device, and pulmonary actinomycosis in smokers with poor dental hygiene), but also that actinomycosis may mimic the malignancy process in various anatomical sites. Bacterial cultures and pathology are the cornerstone of diagnosis, but particular conditions are required in order to get the correct diagnosis. Prolonged bacterial cultures in anaerobic conditions are necessary to identify the bacterium and typical microscopic findings include necrosis with yellowish sulfur granules and filamentous Gram-positive fungal-like pathogens. Patients with actinomycosis require prolonged (6- to 12-month) high doses (to facilitate the drug penetration in abscess and in infected tissues) of penicillin G or amoxicillin, but the duration of antimicrobial therapy could probably be shortened to 3 months in patients in whom optimal surgical resection of infected tissues has been performed. Preventive measures, such as reduction of alcohol abuse and improvement of dental hygiene, may limit occurrence of pulmonary, cervicofacial, and central nervous system actinomycosis. In women, intrauterine devices must be changed every 5 years in order to limit the occurrence of pelvic actinomycosis.
PMCID: PMC4094581  PMID: 25045274
Actinomyces spp.; sulfur granule; osteomyelitis; lumpy jaw syndrome
22.  Safety and feasibility of antibiotic de-escalation in bacteremic pneumonia 
Antibiotic de-escalation is a potential strategy advocated to conserve the effectiveness of broad-spectrum antibiotics. The aim of this study was to examine the safety and feasibility of antibiotic de-escalation in patients admitted with bacteremic pneumonia.
A retrospective chart review was done for patients with bacteremic pneumonia admitted to Northwest Texas Hospital in Amarillo, TX, USA, during 2008. Antibiotic de-escalation was defined as changing the empiric antibiotic regimen to a culture-directed single agent with a narrower spectrum than the original regimen.
Sixty-eight patients were admitted with bacteremic pneumonia. Eight patients were not eligible for de-escalation. Among the 60 patients who were eligible for de-escalation, the treating physicians failed to de-escalate antibiotics in 27 cases (45.0%). Discharge to a long-term care facility predicted failure to de-escalate antibiotics, while an infectious diseases consultation was significantly associated with antibiotic de-escalation. The average daily cost of antibacterial therapy in the de-escalation group was $25.7 compared with $61.6 in the group where de-escalation was not implemented. The difference in mean length of hospital stay and mortality between the two groups was not statistically significant.
Antibiotic de-escalation is a safe management strategy but unfortunately is not widely adopted. Although bacterial resistance poses a significant threat and is rising, antimicrobial de-escalation has emerged as a potential intervention that can conserve the effectiveness of broad-spectrum antibiotics without compromising the patient’s outcome. This practice is becoming important in the face of slow development of new anti-infective agents.
PMCID: PMC4085320  PMID: 25061323
bacteremia; antibiotic de-escalation strategy; lung infection
23.  Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes 
Bacterial infections are becoming increasingly difficult to treat due to widespread antibiotic resistance among pathogens. This review aims to give an overview of the major horizontal transfer mechanisms and their evolution and then demonstrate the human lower gastrointestinal tract as an environment in which horizontal gene transfer of resistance determinants occurs. Finally, implications for antibiotic usage and the development of resistant infections and persistence of antibiotic resistance genes in populations as a result of horizontal gene transfer in the large intestine will be discussed.
PMCID: PMC4073975  PMID: 25018641
gut microbiome; conjugation; natural transformation; transduction
24.  Epidemiology and disease burden of tuberculosis in children: a global perspective 
Our understanding of the tuberculosis (TB) epidemic in children is incomplete due to challenges in diagnosis and reporting. Children have also been largely excluded from research and advocacy. However, the tide appears to be turning and interest in pediatric TB is increasing. In this article, we explore the epidemiology of childhood TB by first reviewing the natural history of TB in children and the factors that impact on each of the stages from exposure to disease. We then discuss how these factors affect what we see at a country and regional level. Finally, we assess the burden of childhood TB globally.
PMCID: PMC4069045  PMID: 24971023
tuberculosis; children; epidemiology; burden; global
25.  Importance of antimicrobial stewardship to the English National Health Service 
Antimicrobials are an extremely valuable resource across the spectrum of modern medicine. Their development has been associated with dramatic reductions in communicable disease mortality and has facilitated technological advances in cancer therapy, transplantation, and surgery. However, this resource is threatened by the dwindling supply of new antimicrobials and the global increase in antimicrobial resistance. There is an urgent need for antimicrobial stewardship (AMS) to protect our remaining antimicrobials for future generations. AMS emphasizes sensible, appropriate antimicrobial management for the benefit of the individual and society as a whole. Within the English National Health Service (NHS), a series of recent policy initiatives have focused on all aspects of AMS, including best practice guidelines for antimicrobial prescribing, enhanced surveillance mechanisms for monitoring antimicrobial use across primary and secondary care, and new prescribing competencies for doctors in training. Here we provide a concise summary to clarify the current position and importance of AMS within the NHS and review the evidence base for AMS recommendations. The evidence supports the impact of AMS strategies on modifying prescribing practice in hospitals, with beneficial effects on both antimicrobial resistance and the incidence of Clostridium difficile, and no evidence of increased sepsis-related mortality. There is also a promising role for novel diagnostic technologies in AMS, both in enhancing microbiological diagnosis and improving the specificity of sepsis diagnosis. More work is needed to establish an evidence base for interventions to improve public and patient education regarding the role of antibiotics in common clinical syndromes, such as respiratory tract infection. Future priorities include establishing novel approaches to antimicrobial management (eg, duration of therapy, combination regimens) to protect against resistance and working with the pharmaceutical industry to promote the development of new antimicrobials.
PMCID: PMC4047980  PMID: 24936131
antimicrobial resistance; antibiotics; National Health Service; methicillin-resistant Staphylococcus aureus; Clostridium difficile; prescribing

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