Clinical significance of the emergence of bacterial resistance in the hospital environment

Antibiotic resistance is an increasing threat in hospitals and both morbidity and mortality from infections are greater when caused by drug-resistant organisms. Whilst hospitals are universally blamed for this increase, there is an insufficient appreciation of external sources of resistance, such as when patients are admitted to hospitals from long-term care facilities in the community. The use of antibiotics in family practice and animal husbandry has also been linked to drug resistance being encountered in the hospital setting. Justifiable hospital antibiotic use, which can be life saving, may lead to 'collateral damage' with the emergence of resistance in non-target bacteria in the bowel, for example, with subsequent spread by cross-infection. At a management level, antibiotic resistance can have a significant impact on the ability of hospitals to maintain services since cohorting of patients and ward closures from outbreaks add to continuing bed shortages and waiting lists. Hospital laboratories must review their standard operating procedures since some resistance mechanisms may be missed by current methods of antibiotic susceptibility testing. With increasing public concern from press reports of 'multiresistant Staphylococcus aureus killer virus' and other drug-resistant organisms, there will inevitably be a push by national authorities for more surveillance data on antibiotic resistance; however, the cost-effectiveness of different surveillance strategies should be considered. Clinical governance and risk management are dominant themes in the National Health Service and hospital hygiene and antibiotic resistance are likely to feature prominently in audits related to these themes in the near future.     

Inappropriate use of antibiotics in croup at three types of hospital.

Despite recent suggestions that bacterial infection is an increasingly important cause of serious croup, most authorities still consider croup a viral disease in which antibiotic therapy is unnecessary. To assess the frequency of antibiotic use in croup among children in hospital, we reviewed the records at three types of hospital in Ontario. Children with evidence of a concurrent infection that might be bacterial were considered to have received antibiotics appropriately. Whereas only 6% of cases at a university-affiliated children''s hospital were inappropriately treated with antibiotics, the proportions at a small rural community hospital staffed by general practitioners and a general hospital staffed by both pediatricians and general practitioners in a medium-sized city were 63% and 38%. Possible reasons for these differences are discussed.     

抗生素的使用情况调查及细菌耐药性分析

目的:分析我院的抗生素的使用频率以及细菌耐药率的变化,为规范临床用药提供参考资料。方法:采用回顾性分析的方法对我院2009年3月-2013年3月收治的8000例住院患者的抗生素使用情况进行调查,并对我院临床上常见革兰阴性菌和阳性菌的耐药率变化进行比较,分析抗生素的使用频率与细菌耐药率变化之间的关系。结果:临床上抗生素的使用频率最大的是β-内酰胺酶抑制剂以及头孢菌素类。金葡菌对环丙沙星的耐药率与青霉素类抗生素的DDDs呈正相关,大肠埃希菌对亚胺培南的耐药率与头孢菌素类抗生素的DDDs呈负相关。结论:抗生素的用药频率与病原菌对抗生素的耐药率有相关性,并且,单一的抗生素并不能引起病原菌的耐药性,而会同时影响其他类型的抗生素的耐药情况。     

Overuse of high stability antibiotics and its consequences in public and environmental health

In this paper the ecological aspects of widespread antibiotic consumption are described. Many practitioners, veterinarians, breeders, farmers and analysts work on the assumption that a antibiotics undergo spontaneous degradation. It is well documented that the indiscriminate use of antibiotics has led to the water contamination, selection and dissemination of antibiotic-resistant organisms, alteration of fragile ecology of the microbial ecosystems. The damages caused by the overuse of antibiotics include hospital, waterborne and foodborne infections by resistant bacteria, enteropathy (irritable bowel syndrome, antibiotic-associated diarrhea etc.), drug hypersensitivity, biosphere alteration, human and animal growth promotion, destruction of fragile interspecific competition in microbial ecosystems etc. The consequences of heavy antibiotic use for public and environmental health are difficult to assess: utilization of antibiotics from the environment and reduction of irrational use is the highest priority issue. This purpose may be accomplished by bioremediation, use of probenecid for antibiotic dosage reduction and by adoption of hospital infections methodology for control resistance in natural ecosystems.     

Improvement of the Management of Infants,Children and Adults with a Molecular Diagnosis of Enterovirus Meningitis during Two Observational Study Periods

Enteroviruses (EVs) are a major cause of aseptic meningitis, and RNA detection using molecular assay is the gold standard diagnostic test. The aim of this study was to assess the impact of an EV positive diagnosis on the clinical management of patients admitted for meningitis over the course of two observational study periods (2005 and 2008–09) in the same clinical departments. We further investigated in multivariate analysis various factors possibly associated with hospital length of stay (LOS) in all age groups (infants, children, and adults). The results showed an overall improvement in the management of patients (n = 142) between the study periods, resulting in a significantly shorter hospital LOS for adults and children, and a shorter duration of antibiotic use for adults and infants. In multivariate analysis, we observed that the time from molecular test results to discharge of patients and the median duration of antibiotic treatment were associated with an increase in LOS in all age groups. In addition, among adults, the turnaround time of the molecular assay was significantly correlated with LOS. The use of CT scan in children and hospital admission outside the peak of EV prevalence in infants tended to increase LOS. In conclusion, the shorter length of stay of patients with meningitis in this study was due to various factors including the rapidity of the EV molecular test (particularly in adults), greater physician responsiveness after a positive result (in adults and children), and greater experience on the part of physicians in handling EV meningitis, as evidenced by the shorter duration of antibiotic use in adults and infants.     

Prescribing patterns of antibiotics and sensitivity patterns of common microorganisms in the Internal Medicine ward of a teaching hospital in Western Nepal: a prospective study

Background

Information about antibiotic use and resistance patterns of common microorganisms are lacking in hospitals in Western Nepal. Excessive and inappropriate use of antibiotics contributes to the development of bacterial resistance. The parameter: Defined daily dose/100 bed-days, provides an estimate of consumption of drugs among hospital in-patients. This study was carried out to collect relevant demographic information, antibiotic prescribing patterns and the common organisms isolated including their antibiotic sensitivity patterns.

Methods

The study was carried out over a 3-month period (01.04.2002 to 30.06.2002) at the Manipal Teaching Hospital, Western Nepal. The median number of days of hospitalization and mean ± SD cost of antibiotics prescribed during hospital stay were calculated. The use of antibiotics was classified for prophylaxis, bacteriologically proven infection or non-bacteriologically proven infection. Sensitivity patterns of the common organisms were determined. Defined daily dose/100 bed-days of the ten most commonly prescribed antibiotics were calculated.

Results

203 patients were prescribed antibiotics; 112 were male. Median duration of hospitalization was 5 days. 347 antibiotics were prescribed. The most common were ampicillin, amoxicillin, metronidazole, ciprofloxacin and benzylpenicillin. Mean ± SD cost of antibiotics was 16.5 ± 13.4 US$. Culture and sensitivity testing was carried out in 141 patients. The common organisms isolated were H. influenzae, E. coli, K. pneumoniae and S. aureus.

Conclusions

Antibiotic resistance is becoming a problem in the Internal Medicine ward. Formulation of a policy for hospital antibiotic use and an educational programme especially for junior doctors is required.     

Changing Use of Surgical Antibiotic Prophylaxis in Thika Hospital,Kenya: A Quality Improvement Intervention with an Interrupted Time Series Design

Introduction

In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals.

Methods

We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design.

Results

From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these.

Conclusion

Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution.     

The Impact of WHO Essential Medicines Policies on Inappropriate Use of Antibiotics

Background

Inappropriate overuse of antibiotics contributes to antimicrobial resistance (AMR), yet policy implementation to reduce inappropriate antibiotic use is poor in low and middle-income countries.

Aims

To determine whether public sector inappropriate antibiotic use is lower in countries reporting implementation of selected essential medicines policies.

Materials and Methods

Results from independently conducted antibiotic use surveys in countries that did, and did not report implementation of policies to reduce inappropriate antibiotic prescribing, were compared. Survey data on four validated indicators of inappropriate antibiotic use and 16 self-reported policy implementation variables from WHO databases were extracted. The average difference for indicators between countries reporting versus not reporting implementation of specific policies was calculated. For 16 selected policies we regressed the four antibiotic use variables on the numbers of policies the countries reported implementing.

Results

Data were available for 55 countries. Of 16 policies studied, four (having a national Ministry of Health unit on promoting rational use of medicines, a national drug information centre and provincial and hospital drugs and therapeutics committees) were associated with statistically significant reductions in antibiotic use of ≥20% in upper respiratory infection (URTI). A national strategy to contain antibiotic resistance was associated with a 30% reduction in use of antibiotics in acute diarrheal illness. Policies seemed to be associated with greater effects in antibiotic use for URTI and diarrhea compared with antibiotic use in all patients. There were negative correlations between the numbers of policies reported implemented and the percentage of acute diarrhoea cases treated with antibiotics (r = -0.484, p = 0.007) and the percentage of URTI cases treated with antibiotics (r = -0.472, p = 0.005). Major study limitations were the reliance on self-reported policy implementation data and antibiotic use data from linited surveys.

Conclusions

Selected essential medicines policies were associated with lower antibiotic use in low and middle income countries.     

Antimicrobial susceptibility of enterococci recovered from commercial swine carcasses: effect of feed additives

Enterococcus faecium is an important nosocomial pathogen often displaying multiple antibiotic resistance. The increase in clinical isolates can be attributed in part to hospital practices in antibiotic usage, but there is concern that antibiotic-resistant strains might also originate in animals fed rations containing antibiotic growth promoters. Ingestion of meat from carcasses contaminated with faecal enterococci might then result in human colonization or resistance gene transfer to human enterococci. Because there are few comparisons of bacteria isolated from matched animals that have, or have not, been fed a diet containing antibiotic, two such groups of pig carcasses were sampled at a commercial abattoir. Forty isolates from each group of pigs were tested for their resistance to avilamycin and tylosin. Although a modest number of pigs was examined, and the number of strains of E. faecium tested was small, there was no evidence that the feeding of a growth promoter caused selection of enterococci resistant to tylosin or avilamycin.     

Oral versus intravenous antibiotics for community acquired lower respiratory tract infection in a general hospital: open,randomised controlled trial.

OBJECTIVE--To see whether there is a difference in outcome between patients treated with oral and intravenous antibiotics for lower respiratory tract infection. DESIGN--Open controlled trial in patients admitted consecutively and randomised to treatment with either oral co-amoxiclav, intravenous followed by oral co-amoxiclav, or intravenous followed by oral cephalosporins. SETTING--Large general hospital in Dublin. PATIENTS--541 patients admitted for lower respiratory tract infection during one year. Patients represented 87% of admissions with the diagnosis and excluded those who were immunocompromised and patients with severe life threatening infection. MAIN OUTCOME MEASURES--Cure, partial cure, extended antibiotic treatment, change of antibiotic, death, and cost and duration of hospital stay. RESULTS--There were no significant differences between the groups in clinical outcome or mortality (6%). However, patients randomised to oral co-amoxiclav had a significantly shorter hospital stay than the two groups given intravenous antibiotic (median 6 v 7 and 9 days respectively). In addition, oral antibiotics were cheaper, easier to administer, and if used routinely in the 800 or so patients admitted annually would lead to savings of around 176,000 pounds a year. CONCLUSIONS--Oral antibiotics in community acquired lower respiratory tract infection are at least as efficacious as intraveous therapy. Their use reduces labour and equipment costs and may lead to earlier discharge from hospital.     

Stronger together? Perspectives on phage-antibiotic synergy in clinical applications of phage therapy

Increasingly, clinical infections are becoming recalcitrant or completely resistant to antibiotics treatment and multidrug resistance is rising alarmingly. Patients suffering from infections that used to be treated successfully by antibiotic regimens are running out of the treatment options. Bacteriophage (phage) therapy, long practiced in parts of Eastern Europe and the states of the former Soviet Union, is now being reevaluated as a treatment option complementary to and synergistic with antibiotic treatments. We discuss some current studies that have addressed synergistic killing activity between phages and antibiotics, the issues of treatment order and antibiotic class, and point to considerations that will have to be addressed by future studies. Overall, co-treatments with phages and antibiotics promise to extend the utility of antibiotics in current use. Nevertheless, a lot of work, both basic and clinical, remains to be done before such co-treatments become routine options in the hospital setting.     

Evaluation of the Short-Term Effects of Antimicrobial Stewardship in the Intensive Care Unit at a Tertiary Hospital in China

Antibiotic abuse can lead to antibiotic resistance, which is a severe problem in China. The purpose of this study is to evaluate the short-term effects of antimicrobial stewardship strategies, including formulary restriction, preauthorization, perioperative quinolone restriction, and control of total antibiotic consumption in the ICU at a tertiary hospital in China. After implementation of antimicrobial stewardship, the total antibiotic consumption in the ICU significantly decreased. The defined daily doses (DDDs) per 100 patient-days decreased from 197.65 to 143.41; however, the consumption of cephalosporins increased from 53.65 to 63.17 DDDs. Significant improvements in resistance to amikacin, gentamicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, and piperacillin in Enterobacteriaceae and resistance to ceftazidime, imipenem, and meropenem in non-fermenting Gram-negative rods were observed. In addition, the initial use of no antibiotics or of a single antibiotic significantly increased (P<0.001) and the use of two antibiotics in combination significantly decreased (P<0.001). Our results demonstrate that implementation of antimicrobial stewardship in a short period in the ICU dramatically reduced antibiotic consumption and significantly improved antibiotic resistance, which leads to more reasonable antibiotic selections by ICU physicians.     

Antibiotic use optimization program in the largest Croatian university hospital--benefits of restrictions on unlimited antibiotic use

The aim of this study was to obtain the relevant information on antibiotic use in a 750-bed Croatian university hospital. The study has been designed as a 2-point prevalence interventional analysis. For each patient on antibiotic therapy, diagnosis, indication for treatment, antibiotic therapy, dosage and route of administration together with the results of microbiological studies (if available) were obtained. After the first prevalence analysis in 2001, a restriction on unlimited antibiotic use was introduced. The second analysis, performed in 2002, after restrictions on antibiotic use, revealed reductions in the rates of restricted release antibiotics and overall antibiotic use with decreases from 38.6% to 36.9% and 23.4% to 23.2% respectively (p = 0.87). The first survey showed that the 5 most often prescribed antibiotics in the therapy of bacterial infections were: gentamicin, other aminoglycosides, carbapenems, amoxycillin +clavulanate and vancomycin with proportions of 14.8%, 10.3%, 8.2%, 7% and 7% respectively. In the year 2002, the most prescribed antimicrobial drugs in the therapy of bacterial infections were: gentamicin, quinolones, vancomycin, carbapenems and cefuroxime with proportions of 18.6%, 11.4%, 9.7%, 9.3% and 8% respectively. A reduction in the proportions of doubtful antibiotic therapy, from 24.6% before the intervention, to 24.2% after the restrictions, accompanied by a 0.4% rise in the rates of indicated antibiotic therapy was also observed (p = 0.93). Our study shows that restrictions on formerly unlimited use of antimicrobials, even when leading to an improvement in their prescribing, do not necessarily cause rapid and significant reduction in the overall use of antibiotics or explicit positive financial effects.     

PYOGENIC INFECTIONS IN ORTHOPEDIC SURGERY—Prevention and Management

A problem that confronts surgeons in clinical practice is that a patient may acquire new infections while in the hospital. When such infections occur they are predominantly staphylococcal and these bacteria are often, but not always resistant to penicillin, streptomycin and the tetracycline antibiotics. They are often but neither completely nor uniformly sensitive to the newer or less frequently used antimicrobial agents.The extension of antibiotic usage from proven situations to “routine” prophylaxis has been a widespread practice. There are many reasons to discourage and to reexamine the validity and purpose, as well as the safety of this practice. We now have sufficient background and experience to revert from widespread and indiscriminate use to a practice of discriminate prophylactic therapy.In general, soft tissue lacerations and clean wounds do not require operation under an “antibiotic umbrella.” Similarly, elective orthopedic surgical procedures of soft tissues such as muscle biopsy, tenorrhaphy and muscle and tendon transplants as well as plastic surgical procedures can be safely performed without antibiotic therapy if technique is good and operation not prolonged. Operations of major magnitude on the motor-skeletal system, such as open fractures, internal fixation of fractures with bone grafts, and major operations of joints are indication for antibiotic therapy for impending infection postoperatively for five days. Reliance is mainly on antistaphylococcal drugs to which hospital organisms are predominantly sensitive. The two remaining indications for antibiotic therapy against impending infection are: (1) major crush injury—for example, to the thigh—and (2) the need for a patient with a healing fracture to have other surgical procedures such as tooth extraction or excision of an infected area which might predispose to transient bacteremia and embolic infection in bone or joint.     

Antibiotic Use in a Small Community Hospital

Audits of medical records were done for similar one-month periods in 1974 and 1977 in a 125-bed community hospital in Hawaii to determine patterns of antibiotic use. One quarter of all hospital patients in both study periods received antibiotics. In 1977 cephalosporins, ampicillin and aminoglycosides were the most commonly used antibiotics. Half of the antibiotics used by surgical specialty departments in both periods were for prophylactic indications. The cost of antimicrobial prophylaxis per patient was reduced by about 57 percent in 1977 compared with 1974. In the 1977 period, 58 percent of patients received proper prophylactic antibiotic regimens; this was statistically higher than the 15 percent of patients given appropriate prophylactic antibiotics in 1974. Fewer than half of the patients in both study periods treated for infections received correct antibiotic therapy. In contrast, 82 percent of infectious disease consultations were considered appropriate by an independent specialist in infectious disease. However, these consultations were obtained in only 15 percent of the patients who received therapeutic antibiotics. It was concluded that audits of patients receiving antibiotics can be effective in the development of appropriate prophylactic surgical regimens. However, during the study period in 1977, we were not able to show large scale improvement in therapeutic antimicrobial use at this community hospital, either by our attempts at physician education or by making infectious disease consultations available.     

Prevention and treatment of nosocomial infections, with special reference to antibiotic policy

Hospital infections are of a major and growing health concern worldwide. They are the cause of appreciable economic loss, but what raises the particular alarm, both ethically and as a public health problem, is their continuous trend towards increasing lethality. The incidence of nosocomial infections can be prevented by creating a system of barriers that would interrupt their spread and transmission. Apart from strict adherence to general hygiene rules and the rational employment of examination methods it is essential in this respect that a prime attention is paid to the sensible use of antimicrobials, i.e. the persuance of a sound antibiotic policy. Its integral components are the systematic laboratory control, continuous epidemiological surveillance of bacterial drug resistance patterns, study of variations in the biological properties of multiple resistant bacterial strains, and the development of, and adherence to, effective and indicated treatment schedules. The particular problems related to bacterial enzyme activities and the genetic information (plasmids) coding for resistance to antimicrobials, as well as the virulence and pathogenicity of agents responsible for the onset of hospital infection are also discussed in this context. It is pointed out that for an effective hospital infection control it is essential to avoid the onesided pressure of badly applied antibiotic therapy.     

Bayesian analysis of a time series of counts with covariates: an application to the control of an infectious disease

This paper presents a Bayesian analysis of a time series of counts to assess its dependence on an explanatory variable. The time series represented is the incidence of the infectious disease ESBL-producing Klebsiella pneumoniae in an Australian hospital and the explanatory variable is the number of grams of antibiotic (third generation) cephalosporin used during that time. We demonstrate that there is a statistically significant relationship between disease occurrence and use of the antibiotic, lagged by three months. The model used is a parameter-driven model in the form of a generalized linear mixed model. Comparison of models is made in terms of mean square error.     

监测血清降钙素原水平以优化重症肺炎的抗感染治疗策略

目的通过监测血清降钙素原（procalcitonin,PCT）在重症肺炎患者中的表达,以优化重症肺炎的抗感染治疗策略。方法选取2011年3月至2013年3月住南京医科大学附属南京医院ICU的重症肺炎患者60例,随机分为常规治疗组（30例）和PCT监测治疗组（30例）。常规治疗组根据病情决定抗菌药物的使用,PCT指导治疗组根据血清PCT水平作为停用抗菌药物的标准。观察两组患者的PSI评分、治疗有效率、住院病死率、住院时间、住院总费用及抗菌药物疗程、抗菌药物费用等。结果PCT监测治疗组的抗感染治疗的疗程、抗菌药物费用以及住院总费用方面,明显低于常规治疗组。而有效率、28d住院病死率及住院时间两组间未见明显差异。结论通过监测PCT可以缩短抗感染药物的疗程,此举避免了抗生素的过度使用并减轻了患者的经济负担。     

Has treatment for childhood gastroenteritis changed?

Because so many children with gastroenteritis in our area were being treated with drugs, which are potentially harmful, we assessed the extent of treatment before admission to hospital of 288 children. Sixty four had been treated: 45 with antibiotic, antidiarrhoeal, or antiemetic drugs and 34 had been given glucose-electrolyte solution, 15 of those had also been given drugs; 119 had had no treatment. Since 1979 there has been a decrease in the use of drugs for gastroenteritis, but glucose-electrolyte mixtures are still underused.