Antibiotic stewardship in low- and middle-income countries: the same but different?

BACKGROUND: Antibiotic resistance (ABR) is a quickly worsening problem worldwide, also in low- and middle-income countries (LMICs). Appropriate antibiotic use in humans and animals, i.e. antibiotic stewardship (ABS), is one of the cornerstones of the World Health Organization's global action plan for ABR. Many LMICs are in the process of developing stewardship programs. AIMS: We highlight challenges for ABS initiatives in LMICs, give an outline of (inter)national recommendations and demonstrate examples of effective, contextualized stewardship interventions. SOURCES: We searched PubMed for articles on ABS interventions in humans in LMICs. Relevant websites and experts were consulted for additional sources. CONTENT: Evidence on effective and feasible stewardship interventions in LMICs is limited, and challenges for implementation of interventions are numerous. Nevertheless, several initiatives at the international and local levels in Latin America, Africa and Asia have shown that ABS effective interventions are feasible in LMICs, although contextualization is essential. IMPLICATIONS: Specific guidance for setting up antimicrobial stewardship programs in LMICs should be developed. Strategic points might need to be progressively addressed in LMICs, such as (a) ensuring availability of diagnostic testing, (b) providing dedicated education in ABR both for healthcare workers and the general public, (c) creating or strengthening (inter)national agencies towards better regulations and audit on production, distribution and dispensing of drugs, (d) strengthening healthcare facilities, (e) exploring a broader synergism between policy makers, academia, professional bodies and civil society and (f) designing and studying easy and scalable ABS interventions for both hospital and community settings.

Infecciones del tracto urinario bajo en adultos y embarazadas: consenso para el manejo empírico / Lower Urinary Tract Infections in Adults and Pregnant Women: A Consensus for Empirical Treatment

Introducción: La infección no complicada del tracto urinario bajo y la bacteriuria asintomática son causas frecuentes de consulta médica ambulatoria y en el servicio de urgencias en Colombia y el mundo. La falta de pautas y consenso para el manejo, así como la emergencia de resistencia a las múltiples opciones terapéuticas disponibles en los uropatógenos provenientes de la comunidad, hacen necesario elaborar unas recomendaciones que orienten al clínico sobre el abordaje óptimo de estas entidades. Objetivo: Definir un consenso sobre el manejo empírico de la bacteriuria asintomática y la infección del tracto urinario (ITU) bajo en adultos y mujeres embarazadas en Colombia. Metodología: Se lleva a cabo una metodología de consenso con expertos en urología, infectología, medicina interna, ginecología y microbiología basada en la revisión de las referencias bibliográficas disponibles en los términos de búsqueda relacionados, haciendo énfasis en estudios locales. Resultados: Se elaboró un algoritmo de manejo para el tratamiento empírico de la ITU baja no complicada en adultos con antisépticos urinarios como nitrofurantoína y fosfomicina trometamol como primera línea, con recomendaciones terapéuticas específicas para el tratamiento de la bacteriuria asintomática en mujeres embarazadas. Adicionalmente, se formuló un algoritmo de decisión para el procesamiento de cultivos de orina. La recurrencia o recaída frecuente justifica remisión a urología e infectología. Conclusiones: Se generan recomendaciones prácticas de fácil implementación en el diagnóstico y manejo de la ITU bajo en adultos y embarazadas, y de los casos donde es necesario tratar la bacteriuria asintomática, con opciones terapéuticas efectivas y de espectro reducido.

Background: Uncomplicated infection of the lower urinary tract and asymptomatic bacteriuria are frequent causes of visits to outpatient clinics and emergency departments in Colombia and worldwide. The lack of guidelines and a consensus for their management, and the emergence of resistance of community-based uropathogens to the available therapeutic options, make it necessary to develop recommendations to guide clinicians on the optimal approach to these entities. Objective: Define a consensus for the empiric management of asymptomatic bacteriuria and Urinary Tract Infection (UTI) in adults and pregnant women in Colombia. Methods: We carried out a consensus methodology with experts in urology, infectious diseases, internal medicine, gynecology and clinical microbiology; based on reviewing the available literature on the related terms, and emphasizing local studies. Results: We developed a management algorithm for the empirical treatment of uncomplicated lower UTI in adults with urinary antiseptics such as nitrofurantoin and fosfomycin trometamol as first line, with specific therapeutic recommendations for the treatment of asymptomatic bacteriuria in pregnant women. Additionally, we created a decision algorithm for processing urine cultures. Frequent recurrence or relapse justifies referral to urology and infectious disease professionals. Conclusions: We generated straightforward and easy-to-implement recommendations for the diagnosis and management of UTI in adults and pregnant women, and in cases where it is necessary to treat asymptomatic bacteriuria, with effective therapeutic and narrow spectrum options.

Resistant gram-negative infections in the outpatient setting in Latin America.

Latin America has a high rate of community-associated infections caused by multidrug-resistant Enterobacteriaceae relative to other world regions. A review of the literature over the last 10 years indicates that urinary tract infections (UTIs) by Escherichia coli, and intra-abdominal infections (IAIs) by E. coli and Klebsiella pneumoniae, were characterized by high rates of resistance to trimethoprim/sulfamethoxazole, quinolones, and second-generation cephalosporins, and by low levels of resistance to aminoglycosides, nitrofurantoin, and fosfomycin. In addition, preliminary data indicate an increase in IAIs by Enterobacteriaceae producing extended-spectrum ß-lactamases, with reduced susceptibilities to third- and fourth-generation cephalosporins. Primary-care physicians in Latin America should recognize the public health threat associated with UTIs and IAIs by resistant Gram-negative bacteria. As the number of therapeutic options become limited, we recommend that antimicrobial prescribing be guided by infection severity, established patient risk factors for multidrug-resistant infections, acquaintance with local antimicrobial susceptibility data, and culture collection.

Intercontinental spread from Israel to Colombia of a KPC-3-producing Klebsiella pneumoniae strain.

In 2008, an increase in the prevalence of carbapenem-resistant Klebsiella pneumoniae was noted in a 286-bed tertiary case hospital in Colombia, where 84 patients (32 infected and 52 colonized) had positive cultures. The identified index patient came from Israel for a liver transplantation. High level carbapenem resistance was observed. Polymyxin B and tigecycline were the only two antibiotics that remained active. PCR-restriction fragment length polymorphism analysis and sequencing revealed blaKPC-3 in the major clone, which was indistinguishable from the K. pneumoniae carbapenemase-3-producing clone described previously in Israel. This exemplifies the threat posed by the global spread of K. pneumoniae carbapenemase-producing pathogens.

New developments in carbapenems.

Antibiotic resistance among Gram-negative pathogens in hospitals is a growing threat to patients and is driving the increased use of carbapenems. Carbapenems are potent members of the beta-lactam family of antibiotics, with a history of safety and efficacy for serious infections that exceeds 20 years. Original and review articles were identified from a Medline search (1979-2008). Reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and package inserts were also used. Carbapenems are effective in treating severe infections at diverse sites, with relatively low resistance rates and a favourable safety profile. Carbapenems are the beta-lactams of choice for the treatment of infections caused by multidrug-resistant organisms. Optimized dosing of carbapenems should limit the emergence of resistance and prolong the utility of these agents. The newly approved doripenem should prove to be a valuable addition to the currently available carbapenems: imipenem, meropenem and ertapenem.

Prevalence of extended-spectrum beta-lactamases in South America.

In South American countries, the class A extended-spectrum beta-lactamases (ESBLs) so far recognised belong to the CTX-M, Pseudomonas Extended Resistance (PER), SHV and TEM families. ESBL rates in South America are among the highest in the world, probably due to multiple factors. SHV- and TEM-type ESBLs have been frequently encountered, but CTX-M is endemic and widely dominant. PER-type ESBLs seem to be restricted to the southern 'cone' of South America. Community-acquired ESBLs are starting to appear.

Evaluation of polymerase chain reaction, adenosine deaminase, and interferon-gamma in pleural fluid for the differential diagnosis of pleural tuberculosis.

STUDY OBJECTIVES: Pleural tuberculosis (TB) is a diagnostic challenge because of its nonspecific clinical presentation and paucibacillary nature. The inefficiency of conventional laboratory methods and the reliance on pleural biopsy have motivated the evaluation of alternative diagnostic strategies. We have evaluated polymerase chain reaction (PCR) directed to the IS6110 sequence of Mycobacterium tuberculosis, the determination of adenosine deaminase (ADA) activity, and measurement of interferon (IFN)-gamma levels in pleural fluid in the diagnosis of pleural TB. PATIENTS: ADA activity, IFN-gamma levels, and PCR were evaluated in 140 cases of pleural effusion, 42 with confirmed pleural TB, 19 with probable pleural TB, 70 with a nontuberculous etiology, and 9 having an undetermined etiology. RESULTS: ADA activity, IFN-gamma levels, and PCR were 88%, 85.7%, and 73.8% sensitive, respectively, and 85.7%, 97.1%, and 90% specific, respectively, for pleural TB that had been confirmed by either culture or pleural biopsy specimens. The combination of PCR, IFN-gamma measurement, and ADA activity determination allowed the selective increase of sensitivity and specificity for probable and confirmed cases compared to individual methods. Positive and negative predictive values for these individual or combined methods were maintained over a wide range of prevalence of pleural TB in the patient population presenting with pleural effusions. Fever and younger age were associated with tuberculous pleural effusion (p < 0. 0001), while blood in sputum and older age were associated with malignant etiology (p < 0.008). CONCLUSIONS: These clinical variables together with the use of ADA activity determination, PCR, and measurement of IFN-gamma levels provide the basis for the rapid and efficient diagnosis of pleural TB in different clinical settings.

Clinical and programmatic mismanagement rather than community outbreak as the cause of chronic, drug-resistant tuberculosis in Buenaventura, Colombia, 1998.

SETTING: Buenaventura, Colombia. OBJECTIVE: To assess whether antituberculosis drug resistance was generated by poor management or community transmission. DESIGN: Treatment-failure and new tuberculosis (TB) patients identified between May 1997 and June 1998 were interviewed and their treatment histories reviewed. Bacteriologic testing, including drug susceptibility profiles (DSP) and DNA fingerprinting by restriction fragment length polymorphism (RFLP), was performed and human immunodeficiency virus (HIV) testing was offered. RESULTS: DSP and RFLP fingerprints were obtained for isolates from 34 of 64 treatment-failure patients; 25 (74%) were resistant to > or = one drug. Fifteen of the 25 patients consented to HIV testing; none were positive. An average of 2.8 major treatment errors per patient was identified. RFLP from the treatment-failure patients revealed 20 unique isolates and six clusters (isolates with identical RFLP); 4/6 clusters contained isolates with different DSP. Analysis of the RFLP from both treatment-failure and new patients revealed that 44/111 (40%) isolates formed 18 clusters. Four of 47 (9%) new patients had multidrug-resistant TB (MDR-TB). Eleven isolates belonged to the Beijing family, related to the MDR strain W. CONCLUSION: Drug resistance in Buenaventura results from both poor management and community transmission. Dependence on DSP to identify TB transmission is inadequate when programmatic mismanagement is common.

[Assessing the functional ability of a group of elderly people using COOP-WONCA charts]. / Medición de la capacidad funcional, con las láminas COOP-WONCA, en una población anciana.

OBJECTIVE: To describe the functional ability of elderly people and analyse its relationship to the use of services. DESIGN: A crossover study. SETTING: An urban population within the metropolitan area of the Community of Madrid. PARTICIPANTS: A random sample of 300 people over 70, taken from the municipal census. MEASUREMENTS AND MAIN RESULTS: Functional ability was measured with COOP-WONCA sheets. 25% of the individuals chosen were excluded due to mistakes in the census. Almost half of the elderly people stated that their health was mediocre or poor; half that their physical ability was limited in some important way; and 37% that their frame of mind caused them some or considerable discomfort. Women perceived their health status as poorer than men did. The number of stated chronic health problems and frame of mind were the most important factors for forecasting use of services. CONCLUSIONS: The prevalence of disturbances in functional ability is high in elderly people. Among the different dimensions of functional ability, frame of mind is that which best forecasts use of primary care clinics.