Endocarditis due to penicillin-sensitive and -resistant pneumococci: the current perspectives on the disease

BACKGROUND: To evaluate the clinic characteristics and therapeutic aspects of endocarditis by Streptococcus pneumoniae sensitive and resistant to penicillin. METHODS: Twelve cases of pneumococcal endocarditis evaluated in 4 Spanish hospitals over the last 10 years were studied, analyzing their clinical characteristics and the existence of resistance to penicillin. The features were compared with a series of 98 cases found in a review of the literature. RESULTS: All the patients were males, most being alcoholics. The course of the disease was acute (2 weeks) in all the cases and evolved with great aggressivity: cardiac failure (9 patients), myocardial abscess (7 patients), multiple arterial embolisms (5 patients), septic arthritis (4 patients). Three patients had simultaneous pneumococcal meningitis but only one had pneumonia. The valve most affected was the aortic (9 cases). Three cases were due to strains of Streptococcus pneumoniae with moderate resistance to penicillin (CMI 0.5-1 micrograms/ml). Global mortality was 42%. All the patients receiving inadequate antibiotic treatment died. Vancomycin and cefotaxime appear to be effective in the treatment of cases produced by strains of pneumococcus with intermediate sensitivity to penicillin. There were no apparent differences in mortality between the cases of endocarditis by pneumococcus sensitive or moderately resistant to penicillin. CONCLUSIONS: Pneumococcal endocarditis continues to condition a high mortality similar to that produced in previously made series. The classic relation with meningitis and pneumonia is infrequent today. The appearance of strains resistant to penicillin may increase the incidence of this infection and further worsen prognosis.     

Strategies in the treatment of penicillin-resistant Streptococcus pneumoniae

The epidemiology, resistance mechanisms, susceptibility testing, treatment, prevention, and clinical importance of penicillin-resistant Streptococcus pneumoniae (PRSP) infection are discussed. PRSP is an established presence in the United States, with some geographic areas reporting decreased susceptibility in up to half of isolates. The mechanism of resistance to beta-lactam antibiotics in S. pneumoniae is genetic changes resulting in decreased binding of drug to the bacterial cell wall. Emerging PRSP strains have necessitated testing as a tool in selecting drugs for treating life-threatening infections. Opinions differ on how to treat these infections empirically. Non-life-threatening infections, such as otitis media, are still often treated successfully with amoxicillin, amoxicillin-clavulanate potassium, or a third-generation cephalosporin. Currently recommended initial treatment of pneumococcal pneumonia in otherwise healthy patients requiring hospitalization consists of cefuroxime, ceftriaxone, or cefotaxime; some authors continue to emphasize injectable penicillin. Once the mainstay of empirical treatment of pneumococcal meningitis, penicillin has largely been abandoned in favor of cefotaxime or ceftriaxone. Vaccination remains an underutilized strategy in atrisk populations. The clinical importance of penicillin resistance among pneumococci is still uncertain. Changing patterns in the susceptibility of S. pneumoniae to penicillin make selection of appropriate therapy increasingly difficult. Key considerations are the site of infection and the level of resistance.     

Thrombotic microangiopathy associated with Streptococcus pneumoniae bacteremia: case report and review

Thrombotic microangiopathy, a disease within the clinical spectrum of thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, was recognized in a previously healthy 50-year-old woman who presented with pneumococcal bacteremia complicated by thrombocytopenia, microangiopathic hemolytic anemia, renal failure, and disorientation. After treatment with plasma exchange and antibiotics, the patient's clinical condition improved. Discontinuation of plasma exchange resulted in a relapse of thrombocytopenia and microangiopathic hemolytic anemia that responded to reinitiation of this intervention. The production of the enzyme neuraminidase by Streptococcus pneumoniae is thought to contribute to the pathogenesis of the thrombotic process. Although pneumococcal infection has been associated with hemolytic-uremic syndrome in children, review of the literature on adults revealed only one such case (in a patient who had undergone splenectomy in the remote past). This report therefore documents an unusual complication of pneumococcal bacteremia in an immunocompetent adult.     

Dynamics of pneumococcal nasopharyngeal colonization during the first days of antibiotic treatment in pediatric patients

BACKGROUND: Nasopharyngeal (NP) carriage of antibiotic-resistant Streptococcus pneumoniae was shown to be associated with recent antibiotic treatment. To date no studies have evaluated early dynamics of pneumococcal NP carriage during antibiotic treatment. OBJECTIVES: To observe changes in NP pneumococcal carriage within 3 to 4 days after initiation of antibiotic treatment in acute otitis media (AOM). METHODS: Patients ages 3 to 36 months with AOM treated with various antibiotics were prospectively followed. Nasopharyngeal culture for S. pneumoniae was obtained before (Day 1) and 72 to 96 h after initiation of treatment (Days 4 to 5). Antibiogram and serotyping were performed in all isolates as was also the MIC of penicillin. The disappearance and persistence of the initial isolates as well as the appearance of isolates with new serotype or with new antibiotic susceptibility patterns were investigated. RESULTS: A total of 120 patients were studied: 106 received beta-lactam antibiotics and 14 received azithromycin. Among the initial 76 pneumococcal isolates 63, 37 and 13% were resistant to > or =1, > or =2 and > or =3 antibiotic drugs. After 3 to 4 days of treatment with various beta-lactam drugs, 45, 63 and 100% of isolates with MIC values of <0.1 microg/ml, 0.125 to 0.25 microg/ml and 0.38 to 1.0 microg/ml, respectively, persisted in the NP (P = 0.038). There was a difference between the various beta-lactam drugs in their effect on NP colonization: a drug with lower MIC values (cefuroxime-axetil) had a better eradication rate of penicillin-susceptible organisms than a less active one (cefaclor), but neither significantly reduced carriage of penicillin nonsusceptible isolates. Azithromycin eliminated carriage of macrolide-susceptible organisms but increased the carriage of macrolide-resistant ones. In 19 of 120 (16%) patients a new S. pneumoniae isolate was recovered 3 to 4 days after initiation of treatment. Of those 16 (84%) were resistant to the drug the patient was receiving. CONCLUSION: A rapid selection of nonsusceptible NP pneumococcal isolates during antibiotic treatment for AOM is common. This phenomenon may contribute to the spread of resistant pneumococci.     

Is Streptococcus pneumoniae a nosocomially acquired pathogen?

Streptococcus pneumoniae is most prominently a major cause of community-acquired infections of the respiratory tract, central nervous system, and bloodstream, but there is an increasing interest in its role in the epidemiology of hospital-acquired infections. Penicillin-resistant pneumococcal strains appeared 3 decades ago and now are present worldwide, often displaying multiple resistance due to antibiotic selective pressure. Horizontal spread can cause either sporadic cases or hospital outbreaks, primarily in younger children and elderly patients. Pneumococcal transmission from one patient to another can be documented by polymerase chain reaction or pulsed-field gel electrophoresis typing. Nosocomial acquisition of infection, along with pediatric age, previous hospitalization, and previous beta-lactam therapy, are the main risk factors significantly associated with penicillin-resistant pneumococcal infections. Nosocomial acquisition also is associated with higher mortality from pneumococcal disease. The importance of penicillin resistance as a risk factor significantly associated with higher mortality from pneumococcal infection is found in some studies, but not in others. Mortality from pneumococcal pneumonia is approximately the same for human immunodeficiency virus (HIV)-infected patients without acquired immunodeficiency syndrome (AIDS) as for HIV-negative subjects, but it is significantly higher in AIDS patients. Penicillin-resistant strains are involved in the vast majority of hospital outbreaks, whether presenting as clinically manifest infection or a simple colonization. Pneumococcal vaccination is recommended universally in order to lower the incidence of invasive infection, although a number of problems can limit its effectiveness.     

Pneumococcal vaccine]

Streptococcus pneumoniae is a common cause of morbidity and mortality in children, immunodeficient individuals and elderly people. As antibiotic resistant strains become more prevalent, pneumococcal infections will become more difficult to manage. Pneumococcal vaccination is inexpensive, and serious side effects are rare. However, the efficacy and safety of the vaccine have been questioned, and the use of vaccination is limited. This article discusses factors to be considered when assessing the indications for pneumococcal vaccination. Immunisation together with a strict policy on the use of antibiotics are our most efficient means for preventing pneumococcal disease and spread of antibiotic resistant strains. Norwegian physicians are encouraged to use pneumococcal vaccine according to the present indications.     

An outbreak of multidrug-resistant pneumococcal pneumonia and bacteremia among unvaccinated nursing home residents

BACKGROUND: Outbreaks of pneumococcal disease are uncommon and have occurred mainly in institutional settings. Epidemic, invasive, drug-resistant pneumococcal disease has not been seen among adults in the United States. In February 1996, there was an outbreak of multidrug-resistant pneumococcal pneumonia among the residents of a nursing home in rural Oklahoma. METHODS: We obtained nasopharyngeal swabs for culture from residents and employees. Streptococcus pneumoniae isolates were serotyped and compared by pulsed-field gel electrophoresis. A retrospective cohort study was conducted to identify factors associated with colonization and disease. RESULTS: Pneumonia developed in 11 of 84 residents (13 percent), 3 of whom died. Multidrug-resistant S. pneumoniae, serotype 23F, was isolated from blood and sputum from 7 of the 11 residents with pneumonia (64 percent) and from nasopharygeal specimens from 17 of the 74 residents tested (23 percent) and 2 of the 69 employees tested (3 percent). All the serotype 23F isolates were identical according to pulsed-field gel electrophoresis. Recent use of antibiotics was associated with both colonization (relative risk, 2.3; 95 percent confidence interval, 1.3 to 4.2) and disease (relative risk, 3.6; 95 percent confidence interval, 1.2 to 10.8). Only three residents (4 percent) had undergone pneumococcal vaccination. After residents received pneumococcal vaccine and prophylactic antibiotics, there were no additional cases of pneumonia, and the rates of carriage decreased substantially. CONCLUSIONS: In this outbreak a single pneumococcal strain was disseminated among the residents and employees of a nursing home. The high prevalence of colonization with a virulent organism in an unvaccinated population contributed to the high attack rate. Clusters of pneumococcal disease may be underrecognized in nursing homes, and wider use of pneumococcal vaccine is important to prevent institutional outbreaks of drug-resistant S. pneumoniae infection.     

Which are the vaccines that human immunodeficiency virus infected patients must receive?

Patients with aids are at increased risk of opportunistic and non opportunistic infections. It is now known that the incidence can be reduced by prophylactic measures and/or the use of vaccines. HIV infection produces an elevated frequency of severe pneumococcal disease with a rate of bacteriemia caused by Streptococcus pneumoniae 150-300 fold greater than rates reported in non-HIV infected people. For this reason, pneumococcal vaccine should be administered as early as possible in the course of the infection. Besides, the antibody response may be significantly higher for asymptomatic persons. Acute hepatitis caused by hepatitis B virus is milder than in non HIV infected patients but chronic disease is more frequent. The prognosis is worse and there is higher risk for infecting another persons. Hepatitis B vaccine is indicated for all the patients with HIV and negative serology for hepatitis B virus. Influenza vaccine is of limited effectiveness due to the high variability of the virus. Besides, influenza incidence is low among approximately young adults, HIV related immunodeficiency increased influenza risk only minimally, the vaccine is administered yearly and HIV-replication can increase in temporal association with vaccination. For all these reasons, fewer hospitalizations and deaths are prevented making it a far less cost-effective prevention strategy than pneumococcal vaccination. The risk of Haemophilus influenzae infections is elevated, but the vaccine is not routinely recommended because the more frequent serotype in HIV infected patients is b. For these subjects, passive immunization with immunoglobulin may also be necessary to provide protection. In conclusion, pneumococcal and hepatitis B vaccination is a reasonable prevention strategy for HIV infected patients at all stages of immunodeficiency. Influenza and H. influenzae vaccination are not recommended and alternative prevention strategies may be done.     

The impact of HIV on Streptococcus pneumoniae bacteraemia in a South African population

OBJECTIVES: To determine the impact of HIV infection on Streptococcus pneumoniae bacteraemia in adults and children by analysing the prevalence and clinical features of such diseases and determining the prevalent serotypes/serogroups and susceptibility patterns of isolates. DESIGN: Patients were identified prospectively from January to October 1996. SETTING: Chris Hani Baragwanath Hospital, Soweto, a tertiary referral hospital treating adults and children, in an urban district near Johannesburg, South Africa. PATIENTS AND METHODS: All patients with S. pneumoniae isolated from blood culture by the Microbiology Department, Chris Hani Baragwanath Hospital were studied. Clinical and microbiological features were recorded. RESULTS: A total of 178 patients with S. pneumoniae were investigated as part of the study; 49 were aged < 13 years. HIV seroinfection was present in 25 (51%) children and 58 (45%) adults. The incidence of S. pneumoniae bacteraemia was 36.9-fold increased in HIV-seropositive children and 8.2-fold increased in HIV-seropositive adults compared with HIV-seronegative individuals. Both adult and paediatric HIV-seropositive patients with S. pneumoniae bacteraemia were significantly younger than HIV-seronegative patients. Pneumonia was a significantly more common presentation in HIV-seropositive children, otherwise the spectrum of disease and outcome were similar in HIV-seronegative and positive groups. Serotype 1 S. pneumoniae isolates were significantly less common in HIV-infected individuals (both adults and children). Resistance to penicillin was increased in S. pneumoniae isolates from HIV-infected patients (significant in adults). Patients with penicillin-resistant isolates did not have a poorer outcome. The potential coverage of serotypes/serogroups included in the proposed nine-valent conjugate pneumococcal vaccine was 88% in HIV-seronegative children and 83% in HIV-seropositive children. The potential coverage of the currently available 23-valent pneumococcal vaccine for adults was 98.2 and 100)% for HIV-infected and HIV-uninfected adults, respectively. CONCLUSION: The burden of bacteraemia due to S. pneumoniae in HIV-seropositive individuals admitted to our hospital is considerable. Differences in the S. pneumoniae serotypes/serogroups in HIV-infected patients have been demonstrated with resultant differences in antibiotic susceptibility patterns. Excellent potential for vaccine coverage was demonstrated for both HIV-seronegative and HIV-seropositive individuals. Further studies are necessary to test the clinical efficacy of pneumococcal vaccination of HIV-seropositive adults and children as a potential preventative measure against this prevalent disease.     

Effect of splenectomy on HIV-related thrombocytopenia and progression of HIV infection in patients with severe haemophilia

Between May 1983 and September 1991 eleven patients with severe haemophilia underwent splenectomy for HIV-related thrombocytopenia. The sustained complete remission rate (platelets > 100 x 10(9)/l) was 82% over a mean follow-up period of 54 months. The group was compared with 22 age-matched non-thrombocytopenic HIV seropositive haemophiliacs who had not undergone splenectomy. Both groups had equivalent use of factor concentrate and there was no significant difference between the groups in terms of anti-retroviral treatment. Analysis of clinical progression of HIV infection and CD4 positive lymphocyte (CD4+) counts, for the time since splenectomy, revealed no significant difference in progression of HIV infection in the splenectomized group compared with the control group. It is concluded that splenectomy is an effective treatment for HIV-related thrombocytopenia and has no adverse effect on the progression of HIV infection.     

Immunogenicity of pneumococcal vaccine in persons with spinal cord injury

OBJECTIVE: To determine immunogenicity and optimum timing for administering the 23-valent pneumococcal vaccine after spinal cord injury (SCI). DESIGN: Double-blind, randomized, placebo control study. SETTING: SCI unit in a tertiary care medical center and community. PARTICIPANTS: Eighty-seven persons with recent SCI. INTERVENTION: Participants were randomized to receive either placebo or pneumococcal vaccine at 16 to 18 days versus 4 to 6 months postinjury. MAIN OUTCOME MEASURES: Antibody concentrations were measured prior to intervention and 1, 2, and 12 months afterward to evaluate the immune response to five serotypes of Streptococcus pneumoniae. Effects of demographic and injury-related variables on immune response were also evaluated. RESULTS: Timing of vaccination did not influence mean antibody concentrations for any serotype (p > .05). Ninety-five percent of vaccinated persons had twofold or greater increases in antibody concentration for at least one serotype when measured 1 month after vaccination versus 35% of placebo groups (p < .01). After 12 months, 93% of vaccinated persons in both groups maintained antibody concentrations twofold or greater than baseline values. CONCLUSIONS: Most participants developed an immune response to at least one serotype that was maintained for at least 12 months. Immune response varied according to serotype. Given the favorable immune response and no effect of timing, persons with SCI should receive pneumococcal vaccine during initial hospitalization.     

Epidemiology of emerging pneumococcal drug resistance: implications for treatment and prevention

Drug-resistant Streptococcus pneumoniae infection are becoming increasingly common throughout the world. These strains pose new challenges in the treatment of suspected pneumococcal infections, and they highlight the importance of limiting selection for resistant strains through judicious antibiotic use and preventing infection by immunization of persons at high risk. The clinical impact of drug-resistant S. pneumoniae infection has not been fully defined, but anecdotal reports suggest that outcome is poor for persons with drug-resistant pneumococcal meningitis. The American Academy of Pediatrics has recommended adding vancomycin to the treatment of suspected pneumococcal meningitis cases until the results of culture and susceptibility testing are available. Additional data are needed to determine the optimal empiric antibiotic regimen for nonmeningeal invasive pneumococcal infections. A 23-valent pneumococcal capsular polysaccharide vaccine can prevent many drug-resistant and susceptible invasive pneumococcal infections. The vaccine is recommended in the United States for persons at increased risk of pneumococcal infection due to certain medical conditions and for all persons > or = 65 years old. Vaccine efficacy for immunocompetent persons > or = 65 years is 75%. However, the vaccine is underutilized, and a substantial reduction in the morbidity and mortality associated with invasive pneumococcal infections is unlikely until the vaccine is used more widely among persons at risk for disease.     

Incidence of postoperative infection or positive culture after facial laser resurfacing: a pilot study, a case report, and a proposal for a rational approach to antibiotic prophylaxis

BACKGROUND: Laser skin resurfacing (LSR) has emerged as a popular procedure for facial rejuvenation; however, there are no clear guidelines regarding systemic antibiotic prophylaxis. OBJECTIVE: We attempt to provide practical guidelines for antibiotic prophylaxis in LSR based on our experiences, pharmacology, and a review of the literature. METHODS: In a pilot study, four consecutive full-face LSR patients were treated without oral or topical antibiotics. The next four patients received oral prophylaxis with a narrow spectrum antibiotic. We also report the case of a severe gram-negative infection after LSR. RESULTS: For full-face LSR, 2 of 4 consecutive patients without antibiotic prophylaxis experienced focal Staphylococcus aureus infection. The next 4 consecutive patients, who had received gram-positive oral prophylaxis, were all culture negative after 2 days. All test sites (5 of 5) were culture negative despite the absence of systemic or topical antibiotics. One patient not in the pilot study receiving gram-positive antibiotic prophylaxis experienced a gram-negative infection. CONCLUSION: We recommend narrow-spectrum gram-positive oral antibiotic coverage for full-face and regional LSR.     

Pneumococci with diminished sensitivity to penicillin in pneumopathies. Clinical consequences

INCREASING PREVALENCE: Since 1988, French clinicians have been faced with an increasing prevalence of penicillin-resistant pneumococcal pneumonia. In 1996, the percentage of strains with reduced susceptibility to penicillin reached more than 40% and the number of multiresistant strains has increased steadily. CLINICAL IMPACT: Despite this apparently alarming situation, the clinical impact is not obvious. Different clinical studies have demonstrated that mortality due to pneumococcal pneumonia has not been affected by the development of resistant strains, eventually because the strains involved belong to less invasive serotypes than penicillin susceptible pneumococci. HYPOTHESIS: The preferential distribution of penicillin resistance among less invasive serotypes might explain the development of resistance in carriage strains more often exposed to antibiotic selection and the greater risk for immunodepressed subjects to acquire these strains. PRACTICAL CONSEQUENCES: To date, first-line antibiotic therapy with amoxicillin at the dose of 3g/24 h remains valid for the great majority of cases. Use of much higher dosages or other antibiotics for pneumococcal pneumonia would only be rational when penicillin minimum inhibitory concentrations are above 2 mg/l.     

Occurrences of penicillin-binding protein 2B gene in clinically isolated penicillin-resistant Streptococcus pneumoniae

We analyzed 88 strains of Streptococcus pneumoniae (S. pneumoniae) isolated in Showa University Hospital from June 1995 to July 1996. The ratios of antibiotic resistance were 39% to penicillin G, 50% to erythromycin, and 2% to imipenem. No resistant to cefotaxime and ofloxacin was observed. Thirty-four strains (39%) were considered to be penicillin-resistant S. pneumoniae (PRSP) strains (MIC of penicillin G > or = 0.5 microgram/ml), according to the breakpoint determined by the Japanese Working Group for Penicillin-Resistant Streptococcus pneumoniae. The ratio of PRSP was higher in S. pneumoniae isolated from inpatients (25/47) when compared to that from outpatients. By PCR analysis, DNA regions of autolysin were amplified in all the 88 strains, confirming that the isolates were S. pneumoniae. Penicillin-binding protein 2B (PBP2B) class B region was positive in 32 strains, and PBP2B class A was in 2 strains. Twenty eight of 34 strains of PRSP contained the PBP2B class B gene. In the remaining six PRSP strains, neither the PBP2B class A nor B region was amplified. The PBP2B class B region was detected as a 180-kb fragment of SmaI digestion of S. pneumoniae DNA by Southern blot analysis, confirming that the detection of PBP2B class B gene by PCR is reliable. We concluded that the PBP2B class B gene is considered to be a major gene responsible for phenotypic resistance of PRSP. We performed genotyping by SmaI digestion pattern using pulsed field gel electrophoresis. No identical pattern was observed in isolates from inpatients, suggesting that apparent nosocomial infection of S. pneumoniae was negligible.     

A prospective crossover randomized trial of novobiocin and rifampin prophylaxis for the prevention of intravascular catheter infections in cancer patients treated with interleukin-2

BACKGROUND: The aim of this study was to determine the efficacy of novobiocin and rifampin as oral antibiotic prophylaxis for the prevention of catheter-related infection in melanoma patients treated with interleukin-2 (IL-2) plus interferon-alpha and chemotherapy (biochemotherapy). METHODS: Patients with advanced melanoma who were treated with biochemotherapy at the University of Texas M. D. Anderson Cancer Center were randomized in a crossover study to receive either oral antibiotic prophylaxis consisting of novobiocin and rifampin or observation alone over a 35-day course period. Patients were subsequently "crossed over" to the opposite arm of the study for an additional 35-day period, with each serving as his or her own control. RESULTS: Twenty-six patients were enrolled. Nine patients (35%) failed to tolerate oral antibiotics because of severe nausea and vomiting; 17 patients (65%) were crossed over and considered evaluable. During the control patient courses, 71% of evaluable patients had infectious complications, 41% had a catheter-associated bacteremia, and 53% had a local catheter infection. In contrast, of the patients treated with antibiotic prophylaxis, only 12% had an infectious complication (P = 0.001), 12% had a local catheter infection (P = 0.008), and 6% had catheter-associated bacteremias (P = 0.04). Thirty-six episodes of catheter infections occurred during the 17 control courses, whereas only 3 episodes occurred during antibiotic prophylaxis (P < 0.001). CONCLUSIONS: Although more than one-third of patients receiving IL-2 treatment with biochemotherapy failed to tolerate novobiocin and rifampin, this oral antibiotic regimen was efficacious in preventing the infectious complications, especially those associated with vascular catheters, in this high risk patient population.     

Screening for Chlamydia trachomatis in asymptomatic women attending family planning clinics. A cost-effectiveness analysis of three strategies

Because of increasing reports of multiple-antibiotic-resistant strains of Streptococcus pneumoniae and associated clinical failures, this study was performed to determine the prevalence of multiresistance among strains from nine Louisiana medical centers. Using a National Committee for Laboratory Standards broth microdilution method, 481 strains were tested. Of these, 70% were penicillin-susceptible (PS), 23% had intermediate minimum inhibitory concentration values to penicillin (I), and 7% were fully resistant to penicillin (PR). The isolation rates (15% to 40% for I strains and 0% to 33% for PR strains) at the various medical centers varied appreciably. The prevalence of penicillin resistance was highest among upper respiratory isolates, while cross-resistance to other antimicrobials varied. The least cross-resistance was noted among PS strains. However, strains with reduced penicillin susceptibility had high levels of cross-resistance. Among I strains, the prevalence of cross-resistance (%) was noted for amoxicillin/clavulanate (6%), cefuroxime (71%), cefaclor (91%), ceftriaxone (13%), cefotaxime (34%), erythromycin (67%), azithromycin (32%), and clarithromycin (32%). For PR strains, the prevalence of cross-resistance was 97% for amoxicillin/clavulanate, cefuroxime, and cefaclor; 67% for ceftriaxone and erythromycin; 89% for cefotaxime; and 69% for azithromycin and clarithromycin. These data emphasize the high prevalence of multiple-antimicrobial-resistance among strains of S pneumoniae with reduced penicillin susceptibility in this geographic area.     

Mortality in geriatric psychiatric inpatients

OBJECTIVE: To report current information about invasive pneumococcal infections, capsular types and antimicrobial resistance in Canada. DESIGN: Retrospective analysis. SETTING: Canada. PATIENTS: A total of 976 patients from whom Streptococcus pneumoniae was isolated from blood or cerebrospinal fluid between Jan. 1, 1992, and Dec. 31, 1995. OUTCOME MEASURES: Capsular type and antimicrobial susceptibility. RESULTS: Twenty types accounted for 90.8% of the isolates from patients over 5 years of age; all but type 15A are covered by the currently available 23-valent vaccine. Nine types accounted for 92% of the isolates recovered from children 5 years and less. Reduced susceptibility to penicillin was found in 7.8% of the collection and was associated with types 6B, 9V and 19A. Full resistance to penicillin was observed most frequently during 1995 and was associated with type 9V. Rates of reduced susceptibility over one 12-month period were 19.5% for trimethoprim-sulfamethoxazole and 4.5% or less for each of cefotaxime, ceftriaxone, chloramphenicol, erythromycin, ofloxacin and tetracycline. CONCLUSIONS: Over 90% of invasive pneumococcal infections are covered by the currently available vaccines (for people over 2 years of age) and the pneumococcal protein-polysaccharide conjugate vaccines under development for young children. The high frequency of antimicrobial resistance observed requires more complete investigation and confirmation; however, taken from a global perspective, it supports the need to develop better control strategies, including greater use of new and existing vaccines.