Resistance to antibiotics: are we in the post-antibiotic era?

Serious infections caused by bacteria that have become resistant to commonly used antibiotics have become a major global healthcare problem in the 21st century. They not only are more severe and require longer and more complex treatments, but they are also significantly more expensive to diagnose and to treat. Antibiotic resistance, initially a problem of the hospital setting associated with an increased number of hospital-acquired infections usually in critically ill and immunosuppressed patients, has now extended into the community causing severe infections difficult to diagnose and treat. The molecular mechanisms by which bacteria have become resistant to antibiotics are diverse and complex. Bacteria have developed resistance to all different classes of antibiotics discovered to date. The most frequent type of resistance is acquired and transmitted horizontally via the conjugation of a plasmid. In recent times new mechanisms of resistance have resulted in the simultaneous development of resistance to several antibiotic classes creating very dangerous multidrug-resistant (MDR) bacterial strains, some also known as "superbugs". The indiscriminate and inappropriate use of antibiotics in outpatient clinics, hospitalized patients and in the food industry is the single largest factor leading to antibiotic resistance. In recent years, the number of new antibiotics licensed for human use in different parts of the world has been lower than in the recent past. In addition, there has been less innovation in the field of antimicrobial discovery research and development. The pharmaceutical industry, large academic institutions or the government are not investing the necessary resources to produce the next generation of newer safe and effective antimicrobial drugs. In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons. The potential negative consequences of all these events are relevant because they put society at risk for the spread of potentially serious MDR bacterial infections.     

Transitional (intravenous to oral) antibiotic therapy

Most clinicians feel the best clinical outcome occurs when patients are treated for serious infections with injections for the entire illness. Unfortunately, this type of prescribing style results in considerable indirect costs such as those involved in increased labor (nursing, pharmacy, intravenous technician time), supplies (needles, syringes, intravenous solutions, administration sets, infusion pumps) and nosocomial bacteremia. It now appears from pharmacodynamic and pharmacoeconomic information that this traditional prescribing behavior should change in the management of many infectious diseases, particularly in those clinically stable patients who can ingest or digest a medication. With the presence of numerous antibiotics with high bioavailability, many infections in such patients can now be successfully treated with an oral agent. This review provides examples of common infections (such as community- and hospital-acquired pneumonias, intra-abdominal infections, urinary tract infections, and skin, soft tissue, and bone infections) in which oral therapy can replace parenteral agents.     

11: Antibiotic resistance

Antibiotic resistance is a consequence of antibiotic use - we need to use antibiotics less and to use them prudently. Plans to combat antibiotic resistance were recently proposed by the World Health Organization, a United States interagency taskforce and the Australian Joint Expert Technical Advisory Committee on Antibiotic Resistance. Prudent antibiotic use includes not using antibiotics when benefit is minimal (eg, in many respiratory tract infections), using narrow-spectrum antibiotics whenever possible and using optimal dosages and regimens. The need for antibiotic therapy can be reduced by preventing infections through vaccination, infection control measures and improved sanitation. Surveillance of antibiotic resistance is needed to target interventions for minimising antibiotic use. More research is needed into new antibiotics and regimens and into improving medical devices and protocols to prevent infection. Some simple changes to practice could reduce development and spread of antibiotic resistance     

重症监护病房（ICU）病人医院感染的临床分析

目的探讨医院重症监护病房（ICU）病人医院感染的临床特点及治疗。方法对我院2006年1月至2008年1月ICU119例医院感染病人从发病部位、基础疾病、感染病原菌种类等进行回顾性分析。结果下呼吸道、泌尿系是医院感染最常见的感染部位,ICU住院病人医院感染的发生与机体抵抗力、医务人员的不规范操作及防患意识的缺乏等因素有关。结论医院感染是目前ICU中威胁病人生命的最严重的疾病及导致病人死亡的主要原因,加强ICU的管理、提高医务人员的防患意识并改进方法、合理应用抗生素等综合措施,能有效减少医院感染的发生。     

Can Surveillance Systems Identify and Avert Adverse Drug Events? A Prospective Evaluation of a Commercial Application

Objective

Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital.

Design and Measurement

We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs.

Results

Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily.

Conclusions

A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs.     

恶性肿瘤患者医院感染120例临床分析

目的 探讨恶性肿瘤患者粒细胞缺乏期发生医院感染的特点及防治对策。方法 回顾性分析我院1997年1月~2003年12月收治的120例恶性肿瘤患者化疗后粒细胞缺乏期医院感染发生的特点,分析感染发生的因素及感染种类等以及治疗效果。结果 发生院内感染的恶性肿瘤患者中,急性白血病患者、肺癌为主(70/120)。感染部位以呼吸道感染最多,占78.89%,其次是口腔粘膜、胃肠道、皮肤及腹腔等。感染种类以细菌为主,真菌感染有明显上升趋势。导致感染的病原菌主要为G-菌,对美罗培南、亚胺培南/西司他丁较敏感。结论 恶性肿瘤患者院内感染机率较高,作好基础护理,肠道消毒及粒细胞刺激因子等,合理使用抗生素,警惕真菌感染等是预防和治疗恶性肿瘤患者医院感染的重要措施。     

Rapid Identification of Hospitalized Patients at High Risk for MRSA Carriage

Patients who are asymptomatic carriers of methicillin-resistant Staphylococcus aureus (MRSA) are major reservoirs for transmission of MRSA to other patients. Medical personnel are usually not aware when these high-risk patients are hospitalized. We developed and tested an enterprise-wide electronic surveillance system to identify patients at high risk for MRSA carriage at hospital admission and during hospitalization. During a two-month study, nasal swabs from 153 high-risk patients were tested for MRSA carriage using polymerase chain reaction (PCR) of which 31 (20.3%) were positive compared to 12 of 293 (4.1%, p < 0.001) low-risk patients. The mean interval from admission to availability of PCR test results was 19.2 hours. Computer alerts for patients at high-risk of MRSA carriage were found to be reliable, timely and offer the potential to replace testing all patients. Previous MRSA colonization was the best predictor but other risk factors were needed to increase the sensitivity of the algorithm.     

Meningitis and encephalitis in infants and children

Despite the availability of modern therapies, meningitis and encephalitis remain potentially life-threatening infections in children with mortality rates reaching up to 25%. Treated patients are at a high risk of long term sequelae including epilepsy, learning, and behavioral disorders. The golden rule of early diagnosis and treatment to achieve a good outcome has not yet been challenged by the new, often expensive antibiotics or contemporary critical care. In this article, an updated overview of meningitis and encephalitis in infants and children is presented. It is important to note that routine childhood immunization has significantly decreased the number of serious infections. However, meningitis and encephalitis remain problematic particularly in developing countries where immunization rates are suboptimal. The most common viral etiologies include enteroviruses, herpes simplex virus, and arboviruses. However, the causative virus may not be identified in up to 70% of cases. This is not the case for bacterial infections unless the patient had received prior oral antibiotics. The causative bacterial organisms vary with age, and the less common fungal infections occur mainly in immune compromised patients.     

恶性肿瘤患者医院感染120例临床分析

目的探讨恶性肿瘤患者粒细胞缺乏期发生医院感染的特点及防治对策。方法回顾性分析我院1997年1月～2003年12月收治的120例恶性肿瘤患者化疗后粒细胞缺乏期医院感染发生的特点，分析感染发生的因素及感染种类等以及治疗效果。结果发生院内感染的恶性肿瘤患者中，急性白血病患者、肺癌为主(70／120)。感染部位以呼吸道感染最多．占78．89％，其次是口腔粘膜、胃肠道、皮肤及腹腔等。感染种类以细菌为主，真菌感染有明显上升趋势。导致感染的病原菌主要为G-菌，对美罗培南、亚胺培南／两司他丁较敏感。结论恶性肿瘤患者院内感染机率较高，作好基础护理，肠道消毒及粒细胞刺激因子等，合理使用抗生素，警惕真菌感染等是预防和治疗恶性肿瘤患者医院感染的重要措施。     

Computerized Surveillance for Adverse Drug Events in a Pediatric Hospital

There are limited data on adverse drug event rates in pediatrics. The authors describe the implementation and evaluation of an automated surveillance system modified to detect adverse drug events (ADEs) in pediatric patients. The authors constructed an automated surveillance system to screen admissions to a large pediatric hospital. Potential ADEs identified by the system were reviewed by medication safety pharmacists and a physician and scored for causality and severity. Over the 6 month study period, 6,889 study children were admitted to the hospital for a total of 40,250 patient-days. The ADE surveillance system generated 1226 alerts, which yielded 160 true ADEs. This represents a rate of 2.3 ADEs per 100 admissions or 4 per 1,000 patient-days. Medications most frequently implicated were diuretics, antibiotics, immunosuppressants, narcotics, and anticonvulsants. The composite positive predictive value of the ADE surveillance system was 13%. Automated surveillance can be an effective method for detecting ADEs in hospitalized children.     

Implementation of an innovative, integrated electronic medical record (EMR) and public health information exchange for HIV/AIDS

Louisiana is severely affected by HIV/AIDS, ranking fifth in AIDS rates in the USA. The Louisiana Public Health Information Exchange (LaPHIE) is a novel, secure bi-directional public health information exchange, linking statewide public health surveillance data with electronic medical record data. LaPHIE alerts medical providers when individuals with HIV/AIDS who have not received HIV care for >12 months are seen at any ambulatory or inpatient facility in an integrated delivery network. Between 2/1/2009 and 1/31/2011, 488 alerts identified 345 HIV positive patients. Of those identified, 82% had at least one CD4 or HIV viral load test over the study follow-up period. LaPHIE is an innovative use of health information exchange based on surveillance data and real time clinical messaging, facilitating rapid provider notification of those in need of treatment. LaPHIE successfully reduces critical missed opportunities to intervene with individuals not in care, leveraging information historically collected solely for public health purposes, not health care delivery, to improve public health.     

Drug-related superinfection in hospitalized patients.

In a series of 14,077 hospitalized medical patients receiving antibiotics, superinfection developed in 95 (0.7%) during drug therapy. The majority were yeast and fungal infections, and serious infections occurred with a frequency of less than one per 1,000 patients treated. Concurrent immunosuppression and impaired renal function increased the risk of new infections.     

Impact of first-line vs second-line antibiotics for the treatment of acute uncomplicated sinusitis

CONTEXT: Studies suggest little benefit in relief of acute sinusitis symptoms from the use of newer and more expensive (second-line) antibiotics instead of older and less expensive (first-line) antibiotics. However, researchers have failed to include development of complications and cost of care in their analyses. OBJECTIVE: To compare the effectiveness and cost of first-line with second-line antibiotics for the treatment of acute uncomplicated sinusitis in adults. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study using a pharmaceutical database containing demographic, clinical (International Classification of Diseases, Ninth Revision), treatment, and charge information for 29 102 adults with a diagnosis of acute sinusitis receiving initial antibiotic treatment between July 1, 1996, and June 30, 1997. MAIN OUTCOME MEASURES: Absence of additional claim for an antibiotic in the 28 days after the initial antibiotic, presence of a claim for a second antibiotic, serious complications of sinusitis, and direct charges and use for the acute sinusitis treatment. RESULTS: There were 17 different antibiotics prescribed in this study. The majority (59.5%) of patients received 1 of the first-line antibiotics. The overall success rate was 90.4% (95% confidence interval [CI], 90.0%-90.8%). The success rate for the 17 329 patients who received a first-line antibiotic was 90.1% and for the 11 773 patients who received a second-line antibiotic was 90.8%, a difference of 0.7% (95% CI, 0.01%-1.40%; P<.05). There were 2 cases of periorbital cellulitis, one in each treatment group. The average total direct charge for patients receiving a first-line antibiotic was $68.98 and a second-line antibiotic was $135.17, a difference of $66.19 (95% CI, $64.95-$67.43; P<.001). This difference was due entirely to the difference in charge of antibiotics and not other charges, such as professional fees, laboratory tests, or emergency department visits. CONCLUSIONS: Patients treated with a first-line antibiotic for acute uncomplicated sinusitis did not have clinically significant differences in outcomes vs those treated with a second-line antibiotic. However, cost of care was significantly higher for patients treated with a second-line antibiotic.     

Monitoring Clostridium difficile infection in an acute hospital: prevalence or incidence studies?

Background

Surveillance of Clostridium difficile infection (CDI) is an essential component of a CDI preventative programme.

Aims

The aim of this study was to evaluate two methods of CDI surveillance.

Methods

Prevalence of CDI, antibiotic use and associated co-morbidity was assessed weekly on two wards over 6?weeks. In addition, CDI incidence surveillance was performed on all new CDI cases over a 13-week period. Cases were assessed for CDI risk factors, disease severity, response to treatment and outcome at 6?months.

Results

Clostridium difficile infection prevalence was 3.5% (range 2.9?C6.1%) on the medical ward and 1.1% (range 0?C3.5%) on the surgical ward. Patients on the medical ward were older and more likely to be colonised with MRSA; however, recent antibiotic use was more prevalent among surgical patients. Sixty-one new CDI cases were audited. Patients were elderly (mean age 71?years) with significant co-morbidity (median age adjusted Charlson co-morbidity score 5). CDI ribotypes included 027 (29 cases) 078 (5) and 106 (4). Eight patients developed severe CDI, seven due to 027. Antibiotic use was common with 56% receiving three or more antibiotics in the preceding 8?weeks. Twenty-four patients had died at 6?months, five due to CDI.

Conclusion

Clostridium difficile infection prevalence gives a broad overview of CDI and points to areas that require more detailed surveillance and requires little time. However, patient-based CDI incidence surveillance provides a more useful analysis of CDI risk factors, disease and outcome for planning preventative programmes and focusing antibiotic stewardship efforts.     

Point-of-care tests for lower respiratory tract infections

Many lower respiratory tract infections (LRTIs) are caused by organisms that do not require antibiotics or could be safely treated with narrow-spectrum antibiotics. Reducing the unnecessary use of antibiotics, particularly broad-spectrum agents, could reduce costs and side effects and delay the emergence of antibiotic-resistant organisms. Various point-of-care tests are becoming available to help clinicians identify the cause of LRTIs at the time of consultation. Point-of-care tests can be used to diagnose influenza, pneumococcal infections, Legionella and respiratory syncytial virus infections, thus allowing early decisions to be made on appropriate management.     

Examining clinical decision support integrity: is clinician self-reported data entry accurate?

The aim of this study was to assess the accuracy of clinician-entered data in imaging clinical decision support (CDS). We used CDS-guided CT angiography (CTA) for pulmonary embolus (PE) in the emergency department as a case example because it required clinician entry of d-dimer results which could be unambiguously compared with actual laboratory values. Of 1296 patients with CTA orders for suspected PE during 2011, 1175 (90.7%) had accurate d-dimer values entered. In 55 orders (4.2%), incorrectly entered data shielded clinicians from intrusive computer alerts, resulting in potential CTA overuse. Remaining data entry errors did not affect user workflow. We found no missed PEs in our cohort. The majority of data entered by clinicians into imaging CDS are accurate. A small proportion may be intentionally erroneous to avoid intrusive computer alerts. Quality improvement methods, including academic detailing and improved integration between electronic medical record and CDS to minimize redundant data entry, may be necessary to optimize adoption of evidence presented through CDS.     

WHONET Software for the Surveillance of Antimicrobial Susceptibility

Continuous surveillance of local antimicrobial susceptibility patterns is a must for combating emerging antimicrobial resistance. WHONET is an effective computerized microbiology laboratory data management and analysis program that can provide guidance for empiric therapy of infections, alert clinicians of trends of antimicrobial resistance, guide drug-policy decisions and preventive measures. The program facilitates sharing of data amongst different hospitals by putting each laboratory data into a common code and file format, which can be merged for national or global collaboration of antimicrobial resistance surveillance. The system can be implemented in hospital laboratories of Armed Forces at no additional cost. Cumulative analysis of surveillance data obtained from various hospitals of Armed Forces at higher centers may help in formulating health policies and control measures at various levels.Key Words: Antimicrobial susceptibility, Surveillance, WHONET     

Surveillance of nosocomial infections by antibiotic monitoring.

Records of all patients receiving intravenous gentamicin sulfate during a 92-day interval were reviewed to detect nosocomial infections that had been missed by routine surveillance. Only 46 of 48 of the 99 treatment courses had been detected. In 96% of cases not detected by routine surveillance, use of gentamicin was considered justified. Of the patients missed by surveillance, 83% were in oncology wards, and 46% had severe neutropenia and fever of unknown origin. Antibiotic surveillance proved a useful adjunct in estimating the incidence of nosocomial infections in such patients.     

The Effects of Peritoneal Dialysis on the Physiological Disposition of Oxacillin, Ampicillin and Tetracycline in Patients with Renal Disease

Seven patients with acute or chronic renal failure who were receiving intermittent peritoneal dialysis and who required parenteral oxacillin, ampicillin or tetracycline were studied to determine the disposition of these antibiotics in severe renal disease and the effects of peritoneal dialysis. While severe renal impairment markedly prolongs persistence in the serum of ampicillin and tetracycline, there is little effect on oxacillin. Whereas required doses of ampicillin and tetracycline are lower in the presence of severe renal disease, oxacillin should be given in doses equivalent to those used for patients with normal renal function. Peritoneal dialysis does not alter these dosage requirements.

Four patients receiving ampicillin or tetracycline in the infusing solution during peritoneal dialysis were studied to determine the amount of systemic absorption. Local prophylaxis alone is not achieved with this method of administration, since small amounts of both antibiotics are absorbed systemically from the infusing solution. The serum concentration of tetracycline attained is inadequate for treatment of systemic infections but is probably significant, with repeated use in intermittent dialysis, in causing adverse effects. Tetracycline should be abandoned in the local prophylaxis of peritonitis during peritoneal dialysis.

     

Restrictive antibiotherapy after renal transplantation.

Forty-two patients were followed up after 44 renal transplantations in an effort to evaluate possible benefits from the following protocol: systematic microbiologic and clinical surveillance, early and aggressive research for the cause of suspected infections, refusal to use prophylactic antibiotherapy, and selection of treatment according to the established cause of the infection. During 18,030 days of follow-up 124 infections were recorded, of which 110 were bacterial, 11 viral and 3 protozoal. Eighty originated in the urinary tract, 17 in skin wounds and 10 in the lower respiratory tract. Septicemia occurred three times, and one death due to infection was recorded. In the treatment of bacterial infections patients received antibiotics for 2486 days. Ampicillin (given for 816 days) and "minor" drugs such as sulfonamides and urinary antiseptics (given for 1036 days) were used 74.5% of the time, whereas gentamicin was used only 2.6% of the time (64 days). Combined antibacterial therapy was needed 1.2% of the time (29 days). A restrictive policy regarding anti-biotherapy seems to be beneficial to renal transplant recipients.