Interactions between antibiotics and human neutrophils in the killing of staphylococci.

Normal and antibiotic-pretreated staphylococci were incubated with human neutrophils to determine the interactions between cells and antimicrobials in the killing of the organisms. Staphylococcus aureus 502A pretreated during log-phase growth with subinhibitory ((1/4) minimum inhibiting concentration) (MIC) concentrations of penicillin G were more susceptible to killing by normal neutrophils than untreated bacteria (intracellular survival 0.17+/-0.04 vs. 1.5+/-0.38%, mean+/-SEM, respectively, at 35 min in 14 experiments; P < 0.01 by t test). Furthermore, this enhanced susceptibility to killing was observed even when phagosome formation was inhibited by cytochalasin B (65.6+/-4.6% pencillintreated vs. 30.5+/-4.5% untreated killed at 30 min in 14 experiments, P < 0.001). Pretreatment of S. aureus with vancomycin similarly enhanced susceptibility to killing by cytochalasin B-treated polymorphonuclear leukocytes (PMN), whereas pretreatment with gentamicin did not. The enchancement of killing by pretreatment with cell wall-active antibiotics was present in a dose-response fashion to 1/16th the MIC. It required specific antimicrobial activity; i.e., penicillin activity was inhibited by penicillinase or by incubation with bacteria at 4 degrees C. It also required active cellular metabolism and intact neutrophils. For antibiotic-pretreated bacteria to be killed by normal and cytochalasin B-treated cells, phagocytosis or binding to the cells was essential via a serum opsonindependent mechanism. In experiments with the cytochalasin B-treated cells, all bound penicillin-treated bacteria were killed vs. only a fraction (70%) of the bound untreated bacteria. Penicillin in 10 times the MIC had no direct effects on PMN phagocytic, metabolic, or microbicidal functions against a nonsusceptible organism, Candida albicans. The results indicate a cooperative effect between cell wall-active antibiotics at low concentrations and human PMN in the killing of staphylococci. The model establishes conditions for the study of the mechanisms involved in the cooperation of these bactericidal systems.

Fungal infection in chronic granulomatous disease. The importance of the phagocyte in defense against fungi.

Among 245 cases of chronic granulomatous disease which were evaluated, fungal infection occurred in 20.4 percent. Fungi encountered include Aspergillus, Torulopsis and Candida. In 18 percent of the patients with fungal infection, the disease was limited to soft tissue or bone; all did well. Most of the patients had fungal pneumonia and/or widely disseminated disease; diagnosis was usually confirmed by open lung biopsy. Patients with pneumonia or disseminated disease who received no therapy succumbed to infection, whereas more than half the patients who received antifungal therapy were cured. Modalities of treatment included antifungal chemotherapy, surgical removal of infected tissue and granulocyte transfusion. Although several patients showed dramatic improvement during granulocyte transfusions given in combination with antifungal chemotherapy, the improvement achieved was not statistically significant when compared with that achieved with chemotherapy alone. These results emphasized the importance of phagocytic cells in defense against fungi and the need for further evaluation of granulocyte transfusion therapy in compromised hosts in whom fungal infections develop.

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.

Dengue and dengue hemorrhagic fever in Latin America and the Caribbean.

Four serotypes of dengue viruses produce dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. They are the most important arbovirus infections of humans, in terms of both morbidity and mortality, constituting one of the most rapidly expanding and re-emerging infectious disease problems in Latin America. In less than 20 years, the region has transformed itself from hypoendemic to hyperendemic, while serotype circulation in most countries has gone from none or single to multiple. Changes in endemicity have coincided with the emergence and increasing incidence of the severer forms of dengue infection. This article reviews the clinical presentations of these diseases. Health care providers who see patients in or returning from areas of Latin America, the Caribbean, and other tropical areas must consider dengue in the differential diagnosis of patients presenting with compatible symptoms, and must be knowledgeable in the current management of this important disease.

Human T-cell lymphotropic virus-I in Latin America.

HTLV-1 infection is endemic in several Latin American countries. HTLV-1-associated myelophathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia lymphoma (ATLL) are emerging diseases in the region. Documented risk factors for acquiring the virus include breast-feeding, contaminated blood transfusion, and sexual intercourse, all of which are amenable to prevention efforts. Strongyloides stercoralis hyperinfection syndrome and therapeutic failure in apparently healthy patients with nondisseminated strongyloidiasis may be markers of HTLV-1 infection. HTLV-1 co-infection may adversely effect the clinical course of scabies and HIV disease. The new enzyme-linked immunosorbent assays (ELISA) are sensitive and specific, and Western blot technology is reliable for differentiating HTLV-1 from less common HTLV-2. HTLV-1 screening of blood donors and individuals with any disorder that suggests infection has become a necessity in Latin America to prevent the spread of this important emerging pathogen.

Fungal infection in Latin American countries.

Fungal infections remain a frequent health problem in Latin American countries. Although these diseases exhibit an extraordinary heterogeneity, they have certain features in common. Most patients belong to low socioeconomic groups and live in rural areas. This article presents a general view of the most prevalent subcutaneous mycoses, with emphasis on epidemiology, clinical manifestations, laboratory diagnosis, and treatment options in the developing countries of Latin America.

Health advice for travelers to Latin America.

Practical and precise information about the potential infectious health hazards that travelers to Latin America may encounter is reviewed in this article. Some diseases are briefly described, others are only mentioned. The countries have been grouped into four geographical areas following the classification of the World Health Organization. The discussion on each area includes information on travelers' diarrhea, malaria, cholera, typhoid fever, yellow fever, and other diseases or special problems.

Skin and wound infection by rapidly growing mycobacteria: an unexpected complication of liposuction and liposculpture. The Venezuelan Collaborative Infectious and Tropical Diseases Study Group.

OBJECTIVE: To describe 10 patients with skin and soft tissue infection caused by rapidly growing mycobacteria after cosmetic liposuction and liposculpture. DESIGN: Case series. SETTINGS: Eight private geographically separate surgical facilities from a single metropolitan area. PATIENTS: Eight patients with definite and 2 with presumptive cases of skin and soft tissue infection caused by rapidly growing mycobacteria after cosmetic surgery procedures during a 24-month period. Microorganisms were isolated from the purulent drainage obtained from wounds or fistulas in 8 cases and were identified as Mycobacterium fortuitum (3 cases) and Mycobacterium abscessus (5 cases) by routine microbiologic techniques. Acid-fast bacilli were observed on Ziehl-Neelsen-stained smears in the 2 remaining cases, but these ultimately failed to grow. In 2 of the surgical units, no apparent environmental predisposing factors were identified after thorough microbiologic environmental investigation. Clinically, all patients exhibited signs of inflammation, microabscesses, and purulent wound drainage within 24 months of abdominal and/or thigh liposuction or homologous fat tissue injection. INTERVENTION: A combined therapeutic approach including surgical drainage, debridment, and prolonged (>3 months) treatment with combined antimicrobial agents including clarithromycin was used in all cases. RESULTS: Nine of 10 patients responded to the combined therapeutic approach, and no evidence of infection was present during at least 12 months of follow-up. CONCLUSION: To our knowledge, this is the first series of patients with rapidly growing mycobacterial infections to be described after liposuction and liposculpture. Rapidly growing mycobacteria should be included in the differential diagnosis of skin and soft tissue infection after cosmetic surgery.

Campylobacter fetus septic arthritis: report of a case.

We report a case of septic arthritis caused by the fastidious gram-negative rod Campylobacter fetus. We suggest that the organism may be part of the endogenous flora and that the clinical infections tend to occur in compromised hosts. Our patient is the first to be described with multiple myeloma and C. fetus septic arthritis. The documented cases of culture-proven C. fetus septic arthritis reported to date have occurred in three men and one woman, all in the seventh and eighth decades of life, with a mono-articular large joint distribution. The septic arthritis always occurred in previously injured joints and curiously enough need not be associated with a toxic-appearing patient. C. fetus infections are also associated with the signs and symptoms of clinical thrombophlebitis. We stress caution in establishing this diagnosis of phlebitis on clinical evaluation only and urge differentiation of true deep vein thrombophlebitis from pseudothrombophlebitis or dissected popliteal synovial cyst. This latter diagnosis may be made non-invasively by ultrasound techniques.

Enhanced killing of penicillin-treated gram-positive cocci by human granulocytes: role of bacterial autolysins, catalase, and granulocyte oxidative pathways.

Staphylococci pretreated with subminimal inhibitory concentrations (subMIC) of cell-wall active antibiotics exhibit increased susceptibility to killing by human polymorphonuclear leukocytes (PMNs), even when phagosome information is impaired by the mold metabolite, cytochalasin B. To investigate the role of specific bacterial factors in the process, studies were carried out with organisms lacking catalase (streptococci) or cell-wall autolytic enzymes and compared to findings with Staphylococcus aureus 502A. Neutrophil factors were studied using inhibitors, oxygen radical scavengers, myeloperoxidase (MPO)-deficient PMNs, or PMNs from a patient with chronic granulomatous disease (CGD). Documentation of the enhanced susceptibility of the streptococcal strains to killing by PMNs following subMIC penicillin pretreatment required the use of cytochalasin B. Enhancement of killing occurred independent of the presence or absence of bacterial autolysins or catalase. SubMIC penicillin pretreatment of S. pneumoniae R36A specifically promoted the susceptibility of these organisms to killing by myeloperoxidase (MPO)-mediated mechanisms (enhancement lost using MPO-deficient or azide-treated cells). Factors other than MPO or toxic oxygen products generated by the PMN respiratory burst are responsible for enhanced killing of penicillin-pretreated S. aureus 502A (enhancement preserved using MPO-deficient, azide-treated, or chronic granulomatous disease patient cells). These studies define methods to study the interaction of antimicrobial agents and PMNs in the killing of microorganisms. They also demonstrate that penicillin treatment can change the susceptibility of gram-positive cocci to the action of specific PMN microbicidal mechanisms. The mechanism of the enhancement appears to be bacterial strain-dependent and not predictable by bacterial autolysin or catalase activity.

Efficacy of ivermectin in the treatment of strongyloidiasis complicating AIDS.

Nine adult male homosexuals who were infected with the human immunodeficiency virus (five with AIDS-defining conditions) and harbored Strongyloides stercoralis received ivermectin on a compassionate basis for persistent intestinal infection. Hyperinfection was present in all cases. Ivermectin was given either as a single oral dose (200 micrograms/kg) or on a multidose schedule (200 micrograms/kg.d) on days 1, 2, 15, and 16. All seven patients who received multiple doses showed sustained clinical and parasitological cure, whereas one of two patients who received single-dose therapy relapsed promptly and fatally. Remissions have been maintained for at least 7 months and up to 3 years of follow-up. Ivermectin appears promising in the treatment of strongyloidiasis in patients with AIDS. Because of the risk of hyperinfection and/or disseminated disease, multidose courses are warranted. We are not aware of other reports describing the efficacy of antiparasitic drugs for strongyloidiasis in patients with AIDS.

Salmonellal splenic abscess in the antibiotic era: a Latin American perspective.

Ten cases of salmonellal splenic abscesses recently documented in various Latin American countries are discussed. All patients were adults; the mean age was 32.6 years, and there was a predominance of males (seven). Predisposing conditions were identified in four cases. All 10 cases were documented by diagnostic imaging techniques; in one case, exploratory diagnostic laparotomy was also performed. Splenectomy was performed on eight patients, while two other patients responded to long courses of intravenous antimicrobial therapy alone. One patient died as the result of perioperative splenic rupture, and two patients underwent second laparotomies because of left subphrenic abscesses. Except for one human immunodeficiency virus-infected individual, all patients were immunocompetent and had large solitary lesions. Salmonella typhi was the predominant organism isolated and was recovered in six of the 10 cases.

Relationship between capsular type, penicillin susceptibility, and virulence of human Streptococcus pneumoniae isolates in mice.

We examined the relationship between penicillin susceptibility, peritoneal virulence in Swiss mice, and capsular type in a selection of 122 clinical Streptococcus pneumoniae isolates belonging to 24 serotypes. Regardless of the serotype, all 32 virulent strains were susceptible to penicillin, and all 41 strains with diminished susceptibility or resistance to penicillin were avirulent. The remaining 49 strains were both susceptible to penicillin and avirulent, irrespective of the serotype. On the basis of their capsular type and pathogenic behavior, strains fell into one of four groups. In the group consisting of serotypes 1, 3, and 4 (n = 16), strains were predominantly virulent (81.3%), and all were penicillin susceptible. In the serotype 6 group (n = 32), the frequency of virulence was significantly lower (34.4 versus 81.3%, P = 0.002), and strains were predominantly penicillin susceptible (71.9%). In the group composed of serotypes 9, 14, 19, and 23 (n = 50), all strains were avirulent, and 56% had decreased susceptibility (n = 12) or resistance to (n = 16) penicillin. The fourth group was heterogenous, as it pooled 24 strains of 15 different serotypes; in this group the frequency of virulence was 33.3%, and strains were predominantly penicillin susceptible (83.3%). These data point to a complex relationship between penicillin susceptibility and virulence in mice but do not entirely separate these characteristics from the role of the capsular type. The possibility that the mechanisms conferring penicillin resistance are related to those leading to a loss of virulence is supported by these findings.

Activities of garenoxacin against quinolone-resistant Streptococcus pneumoniae strains in vitro and in a mouse pneumonia model.

Garenoxacin is a novel des-F(6) quinolone with enhanced in vitro activities against both gram-positive and gram-negative bacteria. We compared the activity of garenoxacin with that of trovafloxacin (TVA) against Streptococcus pneumoniae, together with their efficacies and their capacities to select for resistant mutants, in a mouse model of acute pneumonia. In vitro, garenoxacin was more potent than TVA against wild-type S. pneumoniae and against a mutant with a single mutation (parC), a mutant with double mutations (gyrA and parC), and a mutant with triple mutations (gyrA, parC, and parE). Swiss mice were infected with 10(5) CFU of virulent, encapsulated S. pneumoniae strain P-4241 or its derived isogenic parC, gyrA, gyrA parC, and efflux mutants and 10(7) CFU of poorly virulent clinical strains carrying a parE mutation or gyrA, parC, and parE mutations. The drugs were administered six times, every 12 h, beginning at either 3 or 18 h postinfection. The pulmonary pharmacokinetic parameters in mice infected with strain P-4241 and treated with garenoxacin or TVA (25 mg/kg of body weight) were as follows: maximum concentration of drug in serum (C(max); 17.3 and 21.2 micro g/ml, respectively), C(max)/MIC ratio (288 and 170, respectively), area under the concentration-time curve (AUC; 48.5 and 250 microg. h/ml, respectively), and AUC/MIC ratio (808 and 2000, respectively). Garenoxacin at 25 and 50 mg/kg was highly effective (survival rates, 85 to 100%) against the wild-type strain and mutants harboring a single mutation. TVA was as effective as garenoxacin against these strains. TVA at 200 mg/kg and garenoxacin at 50 mg/kg were ineffective against the mutant with the parC and gyrA double mutations and the mutant with the gyrA, parC, and parE triple mutations. The efficacy of garenoxacin was reduced only when strains bore several mutations for quinolone resistance.

Fungemias por hansenula anómala en el Hospital Privado Centro Médico de Caracas / Fungemia by hansenula anomala in the Hospital Privado Centro Médico of Caracas

Se revisaron en forma retrospectiva las histórias clínicas de todos los pacientes en los cuales se aisló Hansenula anómala en los hemocultivos realizados en el Laboratorio de Microbiología del Hospital Privado Centro Médico de Caracas, en el lapso de 2 años y medio, comprendido entre agosto 1994 y febrero 1997. De 57 pacientes se obtuvo 64 hemocultivos positivos, aislándose 64 especies de Candida. Hansenula anómala se obtuvo en 15 hemocultivos de 15 pacientes diferentes, representando un 26,3 por ciento del total de pacientes, un 23,4 por ciento del total de las candidas y un 30,6 por ciento de las variedades no albicans. La Candida albicans se aisló en 15 pacientes (26,3 por ciento del total). De los pacientes que presentaron Hansenula anómala en sus hemocultivos, el 100 por ciento cumplieron con criterios clínicos de severidad. El rango de edad estaba comprendido entre 1 mes y 76 años, con una media de 43, de los cuales 6 eran masculinos y 9 femeninos. De este grupo de pacientes, 12 ingresaron con patología abdominal, siendo intervenidos quirúrgicamente 10 de estos. De los tres pacientes restantes, dos ameritaron cirugía no abdominal. Todos los pacientes recibieron antibióticos de amplio espectro, nutrición parenteral total y le fue colocado catéteres centrales. Nueve pacientes (60 por ciento) tuvieron criterios de sepsis. Los días de hospitalización oscilaron entre 7 y 101 días, con un promedio de 37. Doce pacientes ameritaron ingreso a la Unidad de Terapia Intensiva. Se inició Anfotericina B en 8 pacientes, con buena respuesta en el 100 por ciento. Seis pacientes recibieron como terapia inicial Fluconazol: 2 con respuesta satisfactoria; 1 fallecido no relacionado con la infección por Hansenula anómala y los tres restantes ameritaron cambio a Anfotericina B. Un paciente no recibió tratamiento antifúngico desconociéndose su evolución.

Tiroiditis aguda bacteriana con presencia de fístula del seno piriforme / Acute bacterian thyroiditis with presentation of fistula periform sinus

Se presenta un caso de tiroiditis aguda bacteriana en una preescolar femenino de 6 años cuya presentación clínica fue: fiebre, disfagia y aumento de volumen en región anterior del cuello. Se instituyó terapia antimicrobiana siendo su evolución tórpida. Posteriormente se detectó ecosonográficamente líquido en región tiroidea, drenándose y obteniéndose material purulento cuyo cultivo reportó flora oral (safnofita). Durante su evolución las pruebas tiroideas fueron normales con excepción del gammagrama tiroideo que reportó hipocaptación importante. Luego del drenaje se practicaron estudios radiológicos con medios de contraste observándose fístula del seno piriforme la cual fue corregida quirúrgicamente. La tiroiditis aguda bacteriana es una entidad raramente reportada en niños en donde la presentación clínica viene precedida de síntomas de infección respiratoria superior, siendo los gérmenes aislados con mayor frecuencia los de la flora oral y existiendo en la mayoría de los casos malformaciones anatómicas preexistentes que condicionan esta enfermedad