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Using interrupted time series analysis to assess associations of fluoroquinolone formulary changes with susceptibility of gram-negative pathogens and isolation rates of methicillin-resistant Staphylococcus aureus.

The use of fluoroquinolones has been linked to increasing bacterial resistance and infection and/or colonization with already resistant pathogens both as a risk factor and based on volume of use. Changes in individual fluoroquinolones used in an institution may also be related to these clinical problems. Interrupted time series analysis, which allows for assessment of the associations of an outcome attributable to a specific event in time, was used to study the effect of changes in our hospital's fluoroquinolone formulary on fluoroquinolone susceptibility rates in select gram-negative pathogens and the methicillin-resistant Staphylococcus aureus (MRSA) isolation rate. Susceptibility rates to ciprofloxacin were considered for the period of 1993 through 2004, while the MRSA isolation rate was assessed from 1995 through 2004. Levofloxacin was added to the formulary in 1999, and gatifloxacin was substituted for levofloxacin in 2001. Statistically significant changes in the already declining rates of susceptibility of Pseudomonas aeruginosa (P, 0.042) and Escherichia coli (P, 0.004) to ciprofloxacin and in the already rising MRSA isolation rate (P, 0.001) were associated with the addition of levofloxacin to the formulary. Substitution of gatifloxacin for levofloxacin on the formulary was associated with reversals in the downward trend in E. coli susceptibility to ciprofloxacin and the upward trend in MRSA isolation rate. No associations were detected on susceptibility of Klebsiella pneumoniae or Proteus mirabilis to ciprofloxacin. These findings suggest that potential changes in susceptibility to fluoroquinolones and isolation of MRSA may vary by both drug and organism.

Anti-Bacterial Agents↗

[New type pathogenic mycoplasmas isolated from female patients with genital infection in Nanjing, China].

OBJECTIVE: To study if infection of new type pathogenic mycoplasmas, Mycoplasma penetrans (Mpe), Mycoplasma fermentans (Mf), and Mycoplasma pirum (Mpi), exists in the genital tract of gynecologic patients with genital infection in China so as to provide information for clinical diagnosis and therapy. METHODS: Cervical secretions from 172 patients with infectious diaseses of gentital tract and 172 healthy controls were collected and inoculated in improved SP-4 culture medium. Biochemical reaction, coagglutination test, metabolism-inhibition test, polymerase chain reaction (PCR) assay, and DNA sequencing were employed to identify the isolated microorganisms. RESULTS: One strain of Mycoplasma penetrans (0.58%) and two strains of Mycoplasma fermentans (1.16%) were isolated from the cervical secretions of patients, but none was found in healthy controls. CONCLUSION: Mpe infection and Mf infection exist in female patients with genital infection in Nanjing.

Adult↗

Activity of four cephalosporin antibiotics in vitro against bovine udder pathogens and pathogenic bacteria isolated from newborn calves.

The in vitro activity of chephaloridine, cephalexin, cefatrizine (BL-S640), and cephapirin (BL-P-1322) was evaluated by the serial dilution method against pathogenic gram-positive and gram-negative bacteria isolated from bovine udders and neonatal calf diseases. Cephapirin showed the comparatively greatest activity against the most common streptococcal species associated with bovine mastitis, whereas cephaloridine exhibited the best activity against Staphylococcus aureus. Cefatrizine was more active than the other cephalosporins against the gram-negative bacteria studied. In general, the minimal bactericidal concentration of each cephalosporin was two- to fourfold lower than the comparative value reported in the literature against the same type of pathogen of human origin.

Animals↗

A comparison of parenteral sulbactam/ampicillin versus clindamycin/gentamicin in the treatment of pelvic inflammatory disease.

60 hospitalized patients with pelvic inflammatory disease entered a randomised study to compare the therapeutic efficacy and tolerability of parenteral sulbactam/ampicillin with that of clindamycin/gentamicin. All 49 pathogens isolated at entry from 21 evaluable patients in the sulbactam/ampicillin group were eradicated. 34 out of 35 pathogens isolated from 18 evaluable patients in the clindamycin/gentamicin group were eradicated. All pathogens resistant to ampicillin in vitro were eradicated. The bacteriological, clinical and overall responses for the sulbactam/ampicillin group were 100%, 85.7% and 85.7%, respectively, compared with 97.1%, 94.4% and 94.4%, respectively, for the clindamycin/gentamicin group. The sulbactam/ampicillin combination was well tolerated.

Ampicillin↗

Comparison of phenotypic and genotypic methods for detection of diphtheria toxin among isolates of pathogenic corynebacteria.

We have compared molecular, immunochemical, and cytotoxic assays for the detection of diphtheria toxin from 55 isolates of Corynebacterium diphtheriae and Corynebacterium ulcerans originally isolated in five different countries. The suitabilities and accuracies of these assays for the laboratory diagnosis of diphtheria were compared and evaluated against the "gold standard" in vivo methods. The in vivo and Vero cell cytotoxicity assays were accurate in their abilities to detect diphtheria toxin but were time-consuming; however, the cytotoxicity assay is a suitable in vitro alternative to the in vivo virulence test. There was complete concordance between all the phenotypic methods. Genotypic tests based upon PCR were rapid; however, PCR must be used with caution because some isolates of C. diphtheriae possessed toxin genes but failed to express a biologically active toxin. Therefore, phenotypic confirmation of toxigenicity for the microbiological diagnosis of diphtheria is recommended.

Animals↗

A randomized clinical trial to compare the effects of a heat and moisture exchanger with a heated humidifying system on the occurrence rate of ventilator-associated pneumonia.

BACKGROUND: The purpose of this study was to compare the performance of heat and moisture exchanger filters with heated humidifying systems in the mechanical ventilator circuit on the incidence of ventilator-associated pneumonia (VAP) and bacterial colonization. METHOD: Two hundred and forty-three consecutive patients who required mechanical ventilation for 48 hours or more in the adult intensive care unit were randomized to either a heat and moisture exchanger (HME) or a heated humidifying breathing circuit. RESULTS: The VAP rate among the group with HME was 11.4%; the rate among the group with heated humidifying system (HHS) was 15.8%. The difference was not statistically significant. Approximately 68% of the patients in the HME group had no pathogen isolated compared with 50% of the patients in the HHS group. This difference was statistically significant (P =.006). However, the distribution of the pathogens among those patients who had the isolated pathogens was mostly identical in the 2 groups. CONCLUSION: Even though the study did not find HME to be significantly advantageous over the HHS, in as much as VAP rate is concerned, other advantages such as reduced nurses workload, reduced financial cost, and better safety made HME a more favorable device for use in our adult intensive care unit.

Bacteria↗

A 10-year experience with bacteriology of acute thoracic empyema: emphasis on Klebsiella pneumoniae in patients with diabetes mellitus.

STUDY OBJECTIVES: To provide an updated evaluation of the bacteriology of acute thoracic empyema for more efficacious treatment. DESIGN: : The medical and microbiological records of all patients who received a diagnosis of acute thoracic empyema were reviewed. Based on the bacteria isolated from the pleural fluid, the patients were classified into the following four groups: aerobic or facultative Gram-positive; aerobic Gram-negative; anaerobic; and mixed. SETTING: A university-affiliated tertiary medical center. PATIENTS AND METHODS: From January 1989 to December 1998, 171 patients with a diagnosis of acute thoracic empyema were treated. A comparative analysis of the isolates from pleural effusions, the mean length of hospital stay, the mean duration of chest tube drainage, the mean duration between the onset of symptoms and the establishment of diagnosis, treatment efficacy, and the need for subsequent intervention was performed. RESULTS: A total of 163 microorganisms were isolated from the pleural fluid of 139 patients. These patients were classified according to the following types of isolates: aerobic or facultative Gram-positive (n = 47); aerobic Gram-negative (n = 59); anaerobic (n = 14); and mixed (n = 19). Klebsiella pneumoniae was the most commonly isolated pathogen (24. 4%) and was strongly associated with a diagnosis of diabetes mellitus. The mortality rate of patients with aerobic Gram-negative bacilli isolated was the highest (22.0%), followed by those with mixed pathogens isolated (15.7%), aerobic or facultative Gram-positive (6.4%), and anaerobic (0%). CONCLUSIONS: The increasing incidence of acute thoracic empyema caused by Gram-negative bacilli, especially by K pneumoniae, has become an increasing problem. The isolation of aerobic Gram-negative bacilli or multiple pathogens from pleural fluid is associated with a poor prognosis and indicates a need for more aggressive antimicrobial chemotherapy.

Acute Disease↗

Clinical predictors of acute bacterial diarrhea in young children.

This prospective study assessed the value of presenting history, physical examination, and screening laboratory tests in predicting whether diarrhea in a young child is associated with a stool culture positive for a bacterial pathogen. Acutely ill children less than 4 years old were studied in a hospital outpatient setting. Two hundred patients were seen in a 9 1/2-month period, which encompassed the seasons of summer, fall, and winter. One hundred ninety-five patients had cultures completed and twenty-nine (15%) had a bacterial pathogen isolated. The best predictive variable for a stool culture positive for a bacterial pathogen was the presence of polymorphonuclear cells in the stool, with a sensitivity of 85%, a specificity of 88%, and positive and negative predictive values of 59% and 97%, respectively. A cluster of three historical variables--abrupt onset of diarrhea, greater than four stools per day, and no vomiting before the onset of diarrhea--was identified that delineated a subpopulation of patients with an increased probability of having a stool culture positive for a bacterial pathogen (27% v 4% if any of the three variables was absent). It is suggested that these findings can be combined in a stepwise manner using the historical cluster as an initial screening, followed by examination for stool polymorphonuclear cells in the high probability subgroup, to identify those patients with a very high probability of having a bacterial pathogen isolated in their stool.

Aeromonas↗

Anti-heart tissue antibodies during experimental infections with pathogenic and non-pathogenic Trypanosoma cruzi isolates in dogs.

Dogs infected with a pathogenic Trypanosoma cruzi isolate (Tc-O), or a non-pathogenic isolate (Tc-D) developed low antinuclear antibody titers throughout 240 days of infection. Dogs infected with Tc-O, but not Tc-D, produced anti-heart tissue antibodies (as measured by an ELISA) throughout infection. Antibody levels were highest immediately after the acute stage of infection (30 days post-inoculation--DPI) when myocardiocyte destruction was at its greatest. Antibody levels progressively declined by 100 DPI, and were almost undetectable by 240 DPI when Tc-O infected dogs developed dilated cardiomyopathy. On Western blots, the anti-heart tissue antibodies recognized an antigen with the same molecular weights (65 and 61 kDa M(r)) recognized by a monoclonal antibody against human beta-adrenoceptors. The results suggest that dogs produce antibodies against heart tissue antigens, possibly the beta-adrenoceptor, during infection with a pathogenic, but not a non-pathogenic, isolate of T. cruzi.

Animals↗

Equine infectious anemia in mules: virus isolation and pathogenicity studies.

There appears to be a lack of information concerning responses of mules to natural infection or experimental inoculation with equine infectious anemia virus (EIAV). In the present study EIAV was isolated from mules, for the first time, and its pathogenicity in naturally infected and experimentally inoculated animals was investigated. Two naturally infected (A and B) and three EIAV free mules (C, D and E) were used for this purpose. Mule A developed clinical signs, whereas mule B remained asymptomatic until the end of the study. Mules C and D were each inoculated with 10ml of blood from mule A and developed signs of the disease; they were euthanatized or died at day 22 and 25 post-inoculation, respectively. Mule E served as a negative control. The virus was isolated from the plasma samples of mules with clinical signs of the disease (A, C and D), but not from the asymptomatic mule B. Both proviral DNA and viral RNA were amplified from blood and tissues of the infected animals by nested polymerase chain reaction (nPCR). Antibodies were not detected in the two experimentally infected mules until their natural death or euthanasia. Clinicopathological and laboratory findings showed that, in mules, EIAV produced clinical signs similar to those observed in horses and ponies. Nested PCR proved to be a rapid, sensitive and specific diagnostic method for the detection of EIAV, regardless of the disease stage.

Animals↗

Differences in genomic DNA sequences between pathogenic and nonpathogenic isolates of Entamoeba histolytica identified by polymerase chain reaction.

A lambda gt11 cDNA library was constructed from the poly(A)+ RNA of trophozoites of Entamoeba histolytica HM-1:IMSS strain. The library was immunologically screened with monoclonal antibody 4G6, which is specific for the 30,000-Mr antigen of pathogenic isolates. A 0.7-kb clone was isolated, and its nucleotide sequence was determined. To examine whether this gene was specific for pathogenic isolates, a polymerase chain reaction was performed by using four sets of primers and the genomic DNA of pathogenic and nonpathogenic isolates as templates. Amplified DNAs were detected not only in pathogenic isolates but also in nonpathogenic isolates. However, when sequences of amplified DNA of these isolates were compared, minor differences were observed. By considering the presence or absence of recognition sites of some endonucleases, it was possible to distinguish between the pathogenic and nonpathogenic isolates. When various isolates with different zymodemes were examined by polymerase chain reaction and enzyme digestion, the results of typing were entirely in accord with those of zymodeme analysis. These results indicate that there is dimorphism in the genomic DNA coding the 30,000-Mr antigen of E. histolytica and that the combined use of the polymerase chain reaction and enzyme digestion is a useful strategy for identification of species and determination of pathogenicity.

Amino Acid Sequence↗

Clinical resistance encountered in the respiratory surveillance program (RESP) study: a review of the implications for the treatment of community-acquired respiratory tract infections.

The Respiratory Surveillance Program (RESP) is a large-scale surveillance study of potential bacterial pathogens from respiratory tract infections that was performed over a 10-month period (July to April) during the 1999-2000 respiratory infection season. It is also the first study of its kind to derive its information entirely from community-based medical practices. This study, therefore, provides insight into the identity, frequency, and susceptibility of the possible pathogens isolated from patients encountered by primary care physicians. Reduction of antibiotic susceptibility in various bacterial pathogens may be of academic interest. However, it is only the emergence of clinical resistance (strains exhibiting minimum inhibitory concentrations above the resistance breakpoint) to commonly used antibacterial agents in the most prevalent species that has significant impact on empiric therapy choices. A review of data from RESP indicated that the most prevalent species were Moraxella catarrhalis, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae. As expected, the prevalence of these bacterial isolates varied by disease state. The prevalence of clinical resistance to various antibiotics ranged, within these 4 species, between 0% and 92%. Resistance to the greatest number of drugs was expressed by S pneumoniae, followed by S aureus, H influenzae, and M catarrhalis. The prevalence of antibiotic resistance found among these community-isolated pathogens was surprisingly similar to that reported in hospital-based studies, suggesting that resistance is as important an issue in the community as it is in hospitals. With few exceptions, the prevalence of resistance was fairly uniform across disease states. The antibiotics most likely to encounter clinically resistant isolates during the treatment of community-acquired respiratory tract infections were penicillins, macrolides, and trimethoprim/sulfamethoxazole. The antibiotics least likely to encounter resistance were quinolones, followed by ceftriaxone and amoxicillin/clavulanate.

Anti-Bacterial Agents↗

In vitro activity of meropenem against common pathogenic bacteria isolated in Taiwan.

The in vitro antimicrobial activity of meropenem, in comparison with nine other antimicrobial agents, against 12 different common pathogenic bacteria were evaluated to know the susceptibility of common bacteria to meropenem in Taiwan. Meropenem was active against most Gram-positive, Gram-negative, and anaerobic bacteria, including methicillin-sensitive Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobacter baumannii, Haemophilus influenzae, and Bacteroides fragilis. For many of them, meropenem was the most active one in comparison with other broad-spectrum cephalosporins, aztreonam, imipenem, and ciprofloxacin. It is concluded that meropenem is a very active agent against most common pathogenic bacteria. It is uncommon for these common bacteria, except MRSA and Stenotrophomonas maltophilia, to be resistant to meropenem in Taiwan, where a high prevalence of resistance to other antimicrobial agents was found in many of the common bacteria.

Anti-Bacterial Agents↗

Antibiotic sensitivity of bacteria isolated in 1998 and 1999 from patients with infections of upper airways residing in Western Pomerania.

Sensitivity to antibiotics of the most common pathogens isolated from the upper airways in north-west part of Poland shown significant regional variation. The rise in resistance to penicillin for Streptococcus pneumoniae (to 22%) and to macrolides for Streptococcus pyogenes, Streptococcus pneumoniae and Staphylococcus aureus was observed. No differences in sensitivity have been found between pathogens isolated from hospital and ambulatory patients.

Anti-Bacterial Agents↗

North American (United States and Canada) comparative susceptibility of two fluoroquinolones: ofloxacin and ciprofloxacin. A 53-medical-center sample of spectra of activity. North American Ofloxacin Study Group.

Ofloxacin, a newer broad-spectrum fluoroquinolone, was evaluated against > 12,000 clinical isolates in a multicenter surveillance trial in the United States and Canada using the standardized disk diffusion method. A total of 53 geographically diverse clinical microbiology laboratories contributed zone diameter results for ofloxacin, ciprofloxacin, and norfloxacin for urinary tract infection (UTI) isolates; and ofloxacin and ciprofloxacin for respiratory tract infection (RTI) isolates, skin and soft tissue infection (SSTI) isolates, and genital tract pathogen isolates. In both the USA and Canada, ofloxacin was shown to have the wide spectrum of activity as follows: RTI isolates, ofloxacin (92.2%-93.8% susceptible) > ciprofloxacin (89.5%-90.4%); SSTI isolates, ofloxacin (87.1%-93.6%) > ciprofloxacin (78.8%-90.4%); UTI isolates, ofloxacin (91.6%-92.5%) > norfloxacin (87.3%-91.7%) > ciprofloxacin (86.4%-89.7%); and genital tract isolates, ofloxacin (94.0%) > ciprofloxacin (85.4%) (Canada only). US strains resistant to ofloxacin were confirmed by reference laboratory tests. Confirmed ofloxacin resistance, other than among staphylococci or nonenteric bacilli, was rare. The species most often found to be resistant to both ofloxacin and ciprofloxacin were methicillin-resistant staphylococci, Acinetobacter spp., and Enterococcus spp. From these contributing US and Canadian laboratory studies, ofloxacin appears to have a balanced spectrum of potential clinical use (91.8% susceptible aerobic isolates), particularly against Gram-positive pathogens and some species resistant to ciprofloxacin. The combined overall isolate (12,241 isolates) rates of susceptibility for ciprofloxacin (four infection sites) and norfloxacin (UTI only) were 87.3% and 88.8%, respectively. Monitoring for increasing fluoroquinolone resistance should be considered, however, as greater use of drugs in this class develops.

Bacteria↗