Clinical and bacteriologic efficacy of telithromycin in patients with bacteremic community-acquired pneumonia.

This retrospective analysis was performed to determine the clinical and bacteriologic efficacy of the ketolide antibacterial telithromycin in patients with community-acquired pneumonia (CAP) with pneumococcal bacteremia. Patients 13 years old with radiologically confirmed CAP and a positive blood culture for Streptococcus pneumoniae at screening were analyzed from eight multicenter Phase III/IV clinical trials. In four open-label, non-comparative studies, patients received telithromycin 800 mg once daily for 7-10 days. In four randomized, controlled, double-blind, comparative studies, patients received telithromycin 800 mg once daily for 5-10 days or a comparator antimicrobial (amoxicillin 1000 mg three times daily, clarithromycin 500 mg twice daily, or trovafloxacin 200 mg once daily) for 7-10 days. In total, 118 patients (telithromycin, 94/1061 [8.9%]; comparator, 24/244 [9.8%]) had documented pneumococcal bacteremia. Those who were treated with telithromycin achieved a clinical cure rate of 90.2% (74/82, per-protocol population); S. pneumoniae was eradicated in 77/82 (93.9%) bacteremic patients who received telithromycin and 15/19 (78.9%) comparator-treated patients. Clinical cure was also observed among telithromycin-treated bacteremic patients who were infected with penicillin- or erythromycin-resistant strains of S. pneumoniae (5/7 and 8/10, respectively). In conclusion, telithromycin achieves high clinical and bacteriologic cure rates in CAP patients with pneumococcal bacteremia.

Continuing professional development and clinical governance: the role of scientific societies.

To date, the rules and state of development of the processes of continuing education and the evaluation of skills and competence vary considerably from one European Member State to another. The recognition of the freedom of establishment of health professionals throughout Europe must be made conditional upon the possession of a given qualification, and also the demonstration of maintained level of expertise, knowledge and skills. This appears to be of primary importance in order to maintain a good quality of care and to improve the performances and responsibilities of the infection of specialists, within the healthcare system. The role of scientific societies such as the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) can be envisaged as follows: (1) to play a key role in the coordination of the processes; definition of the main topics and visions, accreditation of the teaching courses and modalites of evaluation (which supposes a high level of cooperation with the platform for professional qualification) (2) to manage training courses (e.g., ESCMID School, postgraduate courses, technical workshops, educational activities within congresses). In order to make the system clearer and easier to apply, a proposal for a single, comprehensive directive is highly necessary.

Report of working group 3: specialist training and continuing medical education/professional development in the infection disciplines.

The European Union of Medical Specialists (UEMS) core curricula for training in infectious diseases and medical microbiology are adequate with the exception of one deficiency which is the absence of training in epidemiology, public health and infection control. Infectious disease curricula should include training in HIV, tuberculosis, hepatitis and sexually transmitted diseases. There is a need for a core curriculum in infection control. Infection control should have a basis in both medical microbiology and infectious diseases, and should become a specialty dealing with healthcare hygiene in hospitals, in outpatient clinics and also in institutions for the elderly. In the UK, a specialty training in infection is offered and includes internal medicine, clinical infectious diseases and medical microbiology for a total of 9 years. The UEMS should be contacted about the creation of a single specialty of infection, allowing for various degrees of sub-specialisation in infectious diseases or medical microbiology. It is unlikely that a European board examination validating the training of specialists will become a reality soon. Meanwhile, national systems should be created, documenting the content of the training and evaluating the quality of the training institutions. A medical specialist has a constant need for further education. This is generally a national matter, with requirements varying throughout Europe. It should be possible to accumulate continuing medical education/continuing professional development merits on a European level as well as on a national one. With the expansion of the European Union, it is important that the quality and content of specialist training can be verified and training curricula be harmonised. The UEMS should assist in this, in collaboration with scientific societies such as the ESCMID.

[Link between resistance and failure in community-acquired respiratory infections]. / Liens entre résistance et echec dans les infections respiratoires communautaires.

Resistance is one of failure's reasons. We tried, through clinical experience, to approach the magnitude and nature of the links, between phenotypically defined acquired resistance and clinical failure, in community acquired respiratory infections. An efficient resistance mecanism, able to suppress antibiotic action, is clearely associated to a risk of clinical failure (e.g. betalactamase secretion, target modification using methilation for macrolides, target mutation for fluoroquinoles). Resistance mecanism due to reduction of target affinity (pneumococcus and betalactams) progressively decreasing beta lactam activity depending on its expression, is at present time, not clearely associeted with clinical failure. Critical concentration, defining phenotypical resistance, is predictive of failure if it identifies a bacterial population owning an efficient resistance mecanism. It will not be predictive of failure if that concentration do not detect the resistance mecanism (e.g. parC mutation and levofloxacin) or if the link between antibiotic and resistant bacteria is not binary but depends also on pharmacokinetic parameters (pneumococcus and betalactam). Using resistance as a parametre for antibiotic choice, must integrate several elements: presence or not of a resistance mecanism, type and efficiency of the mecanism, links with clinical failure and antibiotic concentration, type and site of infection. Critical concentration is not allways the magic number that predict failure or success.

Toxoplasma gondii infection in advanced HIV infection.

OBJECTIVE: To study Toxoplasma encephalitis (TE) in advanced HIV infection, including predictive factors, possible prophylactic regimens and impact on survival. DESIGN: Epidemiological analysis of data collected prospectively during the Alpha study, a double-blind, randomized clinical trial, comparing two doses of dideoxyinosine in patients with advanced HIV disease. PATIENTS: First episode of TE occurred in 75 out of 499 patients participating in the trial. METHODS: Kaplan-Meier estimates and semi-parametric Cox's model were used. RESULTS: A low CD4 cell count and a positive Toxoplasma serology were strongly predictive of the occurrence of TE. In patients with CD4 counts < 100 x 10(6)/l and a positive Toxoplasma serology at entry to the study, the 12-month TE incidence was 25.4%. Patients who were receiving at entry any of the following potentially antitoxoplasmic drugs: trimethoprim-sulphamethoxazole, pyrimethamine, dapsone, pyrimethamine-sulphadoxine or sulphadiazine, had a lower TE incidence than those who were not; 6.2 versus 18.8%, respectively (P < 0.001). The rate of survival 12 months after TE was 29.6%. Even after adjusting the major prognostic covariates, TE was predictive of death (P < 0.001; relative risk, 1.8). CONCLUSIONS: The high HIV incidence, morbidity and mortality in high-prevalence areas suggests that primary prophylaxis should be given in patients at high risk for toxoplasmic reactivation.

Amoxicillin intestinal absorption reduction by amiloride: possible role of the Na(+) -H+ exchanger.

Intestinal absorption of beta-lactam antibiotics has been shown to use the dipeptide carrier system. In vitro experiments have established that the efficiency of uptake by enterocytes depends on an inwardly directed proton gradient--dipeptides and beta-lactam antibiotics being cotransported along with hydrogen ion. This gradient is thought to result from the sodium-hydrogen (Na(+)-H+) exchanger located on the brush-border membrane. The aim of the present study was to assess the in vivo relevance of these data in humans by examining the effect of amiloride, a well-known inhibitor of the Na(+) -H+ exchanger, on the bioavailability of amoxicillin in eight healthy volunteers. The results show that amiloride reduces significantly amoxicillin absorption rate (mean time to maximum concentration increases from 1.0 to 1.6 hours, p < 0.05) and absolute bioavailability (by 27%, p < 0.01) and that amiloride-induced inhibition of the intestinal Na(+) -H+ exchange could be associated with an additional inhibitory effect on (Na/K)-ATPase activity. The present data seem to confirm the role of Na(+) -H+ exchange in the uptake of beta-lactams by the intestine and to support the indirect sodium dependence of this carrier system in vivo.

Pharmacokinetic interactions between NSAIDs (indomethacin or sulindac) and H2-receptor antagonists (cimetidine or ranitidine) in human volunteers.

The reciprocal effects on pharmacokinetic parameters after a single oral dose of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and sulindac and repeated oral doses of the H2-receptor antagonists cimetidine and ranitidine were determined in two groups of nine healthy subjects each (indomethacin and sulindac groups). Administration of NSAIDs increased the AUC and decreased the oral clearance and apparent volume of distribution of the H2-receptor antagonists without modifying their t1/2. Urinary data and observed modifications in ranitidine and cimetidine metabolites seem to justify a greater increase of H2-receptor antagonist bioavailability with indomethacin (p less than 0.05) than with sulindac (NS). The administration of ranitidine significantly reduced the sulindac volume of distribution without modifying its clearance, which caused an increase in the maximum concentration and a decrease in the t1/2 (p less than 0.05). The effects of cimetidine on the two NSAIDs were more intense than the effect of ranitidine: the decrease in sulindac volume of distribution (p less than 0.02) was accompanied by a significant reduction in sulindac clearance (p less than 0.05). AUC and urinary amounts of sulindac's sulfone metabolite were decreased. These results show that NSAIDs increased the bioavailability of H2-receptor antagonists, and that the latter drugs decrease the volume of distribution of NSAIDs. Furthermore, cimetidine modifies the oxidation metabolism of sulindac.

Tolerance of once-daily dosing of netilmicin and teicoplanin, alone or in combination, in healthy volunteers.

The purposes of this study were to test the pharmacokinetics and renal and otologic tolerances of a once-daily regimen of netilmicin and teicoplanin administered intramuscularly, alone or in combination (4.5 and 6 mg/kg, respectively), for 7 days in 30 healthy male volunteers. Teicoplanin induced only a mild increase in enzymuria. Nephrotoxicity was moderate and reversible with netilmicin; there was increased enzymuria and alteration in diluting ability, without significant changes in urinary beta 2-microglobulin levels, concentrating ability, and glomerular filtration rate. Ototoxicity was not detected in any of the subjects. Our results suggest that (1) teicoplanin and netilmicin given once daily induced only slight, reversible tubular damage, without any sign of ototoxicity; (2) their combination was not more toxic; and (3) clinical studies can be envisaged to evaluate the efficacy and tolerance of once-daily regimens in long-term treatment.

Tuberculosis of the sacroiliac joint: clinical features, outcome, and evaluation of closed needle biopsy in 11 consecutive cases.

Sacroiliac joint (SIJ) involvement has been reported in up to 9.7 percent of patients with skeletal tuberculosis. Lack of awareness of this now uncommon form of infection often leads to diagnostic delay and increased morbidity. Eleven consecutive cases of SIJ tuberculosis are reported; clinical and radiologic features, diagnosis, treatment, and outcome are discussed. Buttock pain was the presenting complaint in all patients. However, radicular pain in the lower back (seven patients) or lower limb (10 patients) was common and in one patient precipitated an unnecessary surgical intervention. SIJ tuberculosis is frequently an isolated phenomenon. Therefore, direct sampling of the SIJ is necessary to establish the diagnosis. The recently described technique of closed needle biopsy of the SIJ was employed in all 11 patients and established the diagnosis in nine of the 11.

Ascites revealing peritoneal and hepatic extramedullary hematopoiesis with peliosis in agnogenic myeloid metaplasia: case report and review of the literature.

A 61-year-old man presented with ascites in the course of agnogenic myeloid metaplasia (AMM). Ascitic fluid was exudative and contained mature and immature leukocytes, erythroid cells, and megakaryocytes as observed on a bone marrow smear. Peritoneal biopsy showed myeloid metaplasia, and liver biopsy revealed intrasinusoidal myeloid metaplasia and peliosis. Ascites cleared after abdominal radiotherapy but treatment resulted in transient aplasia. Subsequently, portal hypertension was demonstrated by hepatic transjugular catheterization. Complications of splenomegaly led to splenectomy and splenorenal shunt followed by fatal acute hepatitis and septic shock. A review of the literature and an analysis of mechanisms of ascites occurring in AMM, especially peritoneal implants of myeloid tissue and occurrence of peliosis in myeloproliferative disorders, are presented.

Nebulized cyclosporine in the rat: assessment of regional lung and extrapulmonary deposition.

BACKGROUND: Nebulized cyclosporine (CsA) has been shown to limit lung allograft rejection as well as intramuscular (IM) CsA, with limited blood diffusion. The present study determined the pharmacokinetic parameters of nebulized CsA, by the assessment of regional lung deposition and extrapulmonary diffusion of CsA. METHODS: CsA was given either by IM injection (10 mg/kg) or by aerosol (at 10 and 25 mg/kg doses); 70 rats were killed at 25 and 50 min, and at 2, 4, 6, 8, 12, 24, or 48 hr after CsA administration. CsA levels were measured in the whole lung, in central and peripheral parts of the lung, in whole blood, kidney, and heart. The areas under the concentration time curves (AUCs) were determined. RESULTS: In blood, kidney, and heart, CsA levels were significantly higher for IM than for aerosol administrations at 10 and 25 mg/kg doses. In the whole lung, the AUC was greater for the aerosol route at 25 mg/kg doses (588 ng x hr/mg) than for the low-dose (200 ng x hr/mg) or IM administration (200 ng x hr/mg). The central to peripheral index of CsA (ratio of AUC central/peripheral part of the lung) was not significantly different for both aerosol administrations (0.63 and 0.69, respectively) and for the IM route (0.81). CONCLUSIONS: Nebulized CsA allows better pulmonary concentration than IM administration, with equivalent central and peripheral deposition whatever the mode of administration, and results in lower levels in blood, kidney, and heart.

Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates.

1. Two in vivo models, in the rat, were used to investigate, in the presence of different substrates, the overall and net intestinal elimination of ciprofloxacin: an open-intestinal perfusion model and an intestinal loop model respectively. 2. In the presence of quinidine, verapamil and cyclosporin (substrates of the P-glycoprotein (P-gp)), plasma AUCs of ciprofloxacin were 1.5 - 2 fold increased, while biliary clearance (1.5 - 2 fold), intestinal overall and net clearances (2 - 4 fold and 1.5 - 8 fold respectively) decreased. The weak effect obtained with cyclosporin as compared to verapamil and especially quinidine, suggests, for ciprofloxacin, the existence of transport systems distinct from the P-gp, as the OCT1 transporter which could be inhibited by quinidine. 3. With cephalexin and azlocillin, two beta-lactam antibiotics, plasma AUCs of ciprofloxacin increased and biliary and intestinal overall clearances decreased in a similar fashion (1.3 - 2 fold), suggesting the involvement of organic anion and/or cation transporters. 4. In the presence of structural analogues, the effect was dependent on the compound administered: Sparfloxacin had no effect on intestinal clearance of ciprofloxacin. In contrast, with pefloxacin, overall intestinal clearance of ciprofloxacin was decreased and net intestinal clearance increased. 5. The specificity of ciprofloxacin intestinal transport appears to be different from P-gp as outlined by the lack of competition with sparfloxacin, a P-gp substrate. Ciprofloxacin intestinal elimination seems to be mediated by organic anion and/or cation transporters and a mechanism sensitive to quinidine and verapamil.

Quinolones in the treatment of lower respiratory tract infections in adult patients.

The potential role of quinolones is discussed on the basis of data obtained during the past 2 years from epidemiological studies, in vitro investigations, animal experiments and clinical trials. Although the newest compounds exhibit good activity against Streptococcus pneumoniae and intracellular pathogens in animal models, the role of quinolones as first line therapy in community-acquired pneumonia is still debatable and may be modified according to clinical presentation and the rate of resistance of pneumococci to beta-lactams and macrolides. Cost-utility and cost-benefit studies are required to delineate precisely the role of quinolones in the treatment of acute exacerbations of chronic bronchitis. In addition, promising results indicating a possible future for the clinical use of quinolones in the therapy of mycobacterial infections have been obtained.

What is the place of fluoroquinolones in the treatment of community-acquired respiratory tract infections?

The newest (third generation) fluoroquinolones are potentially useful agents in the management of community-acquired respiratory tract infections. This is mainly due to their increased activity against Streptococcuspneumoniae, a pathogen poorly susceptible to the second-generation compounds, and playing a major role in upper and lower respiratory tract infections. Also, their spectrum includes the other main pathogens involved in those infections, comprising Haemophilus influenzae and intracellular agents, against which the newest fluoroquinolones exhibit a similar activity to that of the previous compounds. The pharmacokinetic and pharmacodynamic properties of the newest quinolones make them suitable for effective therapy of lower respiratory tract infections. However, careful attention should be paid to the dose and dosing regimen of each compound in clinical usage in order to select the most adapted drug. In clinical trials, the fluoroquinolones have been shown to be at least as effective as the comparators in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis (AECB) or sinusitis, including documented pneumococcal infections. Their tolerance is generally considered to be good. The main question regarding the fluoroquinolones in the treatment of community-acquired respiratory tract infections is their role as first-line agents used in single drug therapy. Cost-effectiveness studies are needed to define this role further. Identification of subpopulations of patients at risk of being infected by penicillin-resistant pneumococci or Gram-negative bacilli who could benefit from a fluoroquinolone could be useful. Also, it must be considered that a large use of fluoroquinolones as first-line agents in very common infections such as AECB or sinusitis could contribute to the selection of bacteria, including S. pneumoniae, resistant to this class of antibiotics. Careful control of fluoroquinolone usage and development of bacterial resistance is of great importance.

Cefotaxime optimal dosage in adult patients. A reappraisal.

Cefotaxime, a third generation cephalosporin, is used throughout the world over a wide range of doses. The purpose of this paper is to discuss the rationale for determination of the optimal dosage and of adequate modes of administration. Among the factors determining in vivo activity, the most important are: (1) the time dependence of the antibacterial effect of cephalosporins, (2) the limited effect of increasing the drug concentration in contact with the bacteria and (3) the absence of a significant post-antibiotic effect. Combined with the rather short elimination half-life of cefotaxime, these factors argue for the use of a unitary dose of 1g in adult patients and for a 6- or 8-hour interval between doses. Information obtained from various animal models of infection are discussed. Clinical and bacteriological studies published in the international literature report a high rate of cure (between 80 and 100%) according to the type of infection and to the criteria of efficacy, with daily doses ranging from 2 to 4g bid or qid. The results obtained with the lowest doses are detailed, particularly for infections permitting the use of a low dosage. The necessity for increasing the dose is discussed in the following situations: (1) in specific infections requiring high local drug concentrations such as meningitis and endocarditis, (2) against micro-organisms exhibiting moderate susceptibility to cefotaxime (MIC greater than or equal to 1 mg/L) and (3) in immunocompromised patients. It is now well established that third generation cephalosporins have to be combined with other antimicrobial agents (e.g. aminoglycosides) for the treatment of patients with infections caused by bacteria able to become resistant. For susceptible strains, it has not been established that a synergistic effect of cefotaxime with another agent allows a reduction of the dosage of each member of the combination.

Inappropriateness and variability of antibiotic prescription among French office-based physicians.

OBJECTIVE: To describe oral antibiotic prescription in the community. DESIGN: Audit of anti-infective prescribing in office-based medical practice. SETTING: Center of France, in the Loiret, a 600,000 inhabitant administrative division. MAIN OUTCOME MEASURES: Clinical hypothesis and antimicrobial drugs used as well as daily doses and durations of treatment. RESULTS: Respiratory tract infections with a presumed viral etiology accounted for 36% of prescriptions. In children, a high percentage of antibiotic prescriptions were underdosed as compared to clinical recommendations, particularly in acute otitis media. The variability of the daily dose was high, with coefficients of variation over 40% in acute otitis media or acute tracheobronchitis. Whatever the clinical hypothesis, the duration of treatment was close to 8 days. In acute otitis media, the coefficient of variation was 14%, the lowest for all diagnoses. CONCLUSION: Our investigation identified two main areas for improving antimicrobial drug prescribing: (1) reduction of useless prescriptions in respiratory tract infections with a presumed viral etiology, and (2) increasing the prescribed daily dose of antimicrobials to the recommended levels.

Community-acquired pneumonia. Importance of initial noninvasive bacteriologic and radiographic investigations.

During a one-year epidemiologic survey of acute community-acquired pneumonia, we prospectively investigated in 116 adult nonimmunocompromised patients (a) the importance of initial noninvasive investigations (ie, blood culture and quantitative sputum culture) and the value of the initial radiologic type of pneumonia in diagnosing of the etiologic agent, and (b) the management of pneumonia. Quantitative sputum culture or blood culture (or both) permitted bacteriologic diagnosis in 44 percent of the cases. The radiologic types found were segmental or alveolar densities in 75 patients (65 percent), patchy alveolar densities in 11 (9 percent), mixed opacities in 26 (22 percent), and interstitial infiltrates in four (3 percent). We observed that (a) the prognosis was identical whether a bacteriologic diagnosis was made or not, (b) the Gram stain, an inexpensive procedure, was as contributive for bacteriologic diagnosis as quantitative sputum culture, diagnosis as (c) blood cultures were poorly contributive in patients without severe infections, and (d) alveolar densities were associated with a bacterial infection in 90 percent of the cases of known etiology. On the basis of these results, a pragmatic strategy of initial management of community-acquired pneumonia is proposed.

Clinical evaluation of the management of community-acquired pneumonia by general practitioners in France.

STUDY OBJECTIVES: To evaluate the management of community-acquired pneumonia (CAP) by general practitioners (GPs) in terms of clinical efficiency and adherence to official recommendations. DESIGN: Prospective cohort study. SETTING: Community-based study from 11 French counties. PATIENTS: Adult patients clinically suspected of having CAP who were seen by GPs were included after confirmation of the presence of an infiltrate on chest radiographs. INTERVENTION: The management of the patients was left to the discretion of the GP. MEASUREMENTS AND RESULTS: One hundred thirty patients were included in the study, and 13 patients (10%) were immediately hospitalized because of the severity of the pneumonia. The remaining 117 patients were treated as outpatients: 108 of 117 patients (92%) were cured, and 9 patients were subsequently hospitalized because of the failure of ambulatory treatment. Diagnostic error (n = 6) rather than antibiotic failure (n = 3) was the most frequent cause of the failure of ambulatory treatment. Only 40% of the patients received an initial antibiotic treatment that was in agreement with French recommendations. However, the rate of antibiotic failure leading to hospitalization was low (3 of 117 patients; 2.6%) and similar for patients treated or not according to recommendations (p > 0.5). Overall, five patients (4%) died; all deaths occurred during hospitalization and were related to the severity of the underlying disease but not to the choice of antibiotic treatment. CONCLUSIONS: The management of CAP by GPs was clinically effective despite a poor adherence to official recommendations. Our results suggest that adequate assessment of severity rather than adherence to recommendations for antibiotic treatment had an impact on clinical outcome of CAP managed by GPs.

AIDS-related conditions: study of a representative sample of 1203 patients deceased in 1992 in France.

BACKGROUND: Little representative information exists on the frequency of human immunodeficiency virus (HIV)-related diseases among the overall AIDS population. The objective of this research is to assess the nature, frequency and characteristics of these diseases among AIDS patients during their last year of life and to analyse these frequencies according to the mode of transmission and other socio-demographic and medical characteristics. METHODS: To obtain comprehensive data, we conducted an investigation based on retrospective collection of clinical information on a representative sample (1203 deaths) of all AIDS deaths that occurred in France during 1992. RESULTS: The frequency of the diseases was markedly higher than the one described in the AIDS surveillance registers and varied between homosexuals and intravenous drug users (IVDU). After controlling for other variables (age, CD4 counts, survival times) by means of logistic regression, homosexuality remained a significant explaining factor for Kaposi's sarcoma, cytomegalovirus infections, herpes simplex and cryptosporidiosis. In contrast, HIV encephalopathy, hepatitis, mental disorders, invasive candidiasis and cachexia were more frequent in male IVDU. Few differences were observed by sex. CONCLUSIONS: Several factors may explain the differences: variation in exposure to infectious agents, general health status, use of medical care and direct influence of the mode of HIV transmission. These data are of particular value for medical services in planning the magnitude of health care needs among the AIDS population overall, for clinicians and researchers for advancing the understanding of the natural history of AIDS and in the definition of prophylactic strategies against opportunistic infections.

Antibiotic use in developing countries.

Antimicrobials have been used successfully for over 6 decades, but genes expressing resistance to them have emerged in strains of bacteria and have disseminated through the global ecosystem to reach infecting microorganisms, produce disease, and seriously interfere with therapy, allowing infections to progress and kill despite antibiotic administration. The upsurge in prevalence of such resistance genes in the bacterial population that colonize and infect humans involves two processes, emergence and dissemination, in both of which there have been contributions from the developing world, where resistance is common and increasing. The emergence of pneumococcal isolates noted in Papua New Guinea and later in South Africa that 1 decade later spread to most of the world and the intercontinental spread between the United States and Venezuela of a new gentamicin resistance gene carried on an epidemic plasmid are examples of the ability of bacteria to travel freely, without regard to borders. Complex societal issues such as the misuse of antibiotics by physicians, pharmacists, and the public; the suboptimal quality of the drugs (emergence); and conditions such as crowding, lack of hygiene, poor or nonexistent hospital infection control practices, or insufficient surveillance (dissemination) play a largely unmeasured role that requires study and solutions. In the meantime, we may intervene to delay the emergence of resistance and to limit its spread by promoting the judicious use of antibiotics both at the local level as well as from multinational organized cooperative efforts. Education and improvement of surveillance and socioeconomic conditions are integral parts of any solution strategy.