K.B. Waites

Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns.

Ureaplasma urealyticum, a common commensal of the urogenital tract of sexually mature humans, is gaining recognition as an important opportunistic pathogen during pregnancy. While its etiologic significance in many aspects of adverse pregnancy remains controversial, recent evidence indicates that U. urealyticum in the absence of other organisms is a cause of chorioamnionitis. Furthermore, ureaplasmal infection of the chorioamnion is significantly associated with premature spontaneous labor and delivery. In at least some cases, it appears to be causal. Present evidence indicates that U. urealyticum is a cause of septicemia, meningitis, and pneumonia in newborn infants, particularly those born prematurely. There is strong but not definitive evidence that ureaplasmal infection of the lower respiratory tract can lead to development of chronic lung disease in very low-birth-weight infants. Although risk factors for colonization of the lower genitourinary tract have been identified, little information is available concerning risk factors for intrauterine infection and host immune responses to invasive infection. Recent establishment of animal models of respiratory and central nervous system diseases should provide an opportunity to evaluate risk factors, pathogenic mechanisms, and operative immune mechanisms. However, the most critical need is additional information concerning indications for diagnosis and treatment as well as efficacy of treatment. Images

ASSOCIATION OF UREAPLASMA UREALYTICUM INFECTION OF THE LOWER RESPIRATORY TRACT WITH CHRONIC LUNG DISEASE AND DEATH IN VERY-LOW-BIRTH-WEIGHT INFANTS

Endotracheal aspirates from 200 infants who weighted less than or equal to 2500 g and who had evidence of respiratory disease were cultured within 24 h of birth for mycoplasmas, chlamydiae, viruses, and bacteria to evaluate the relation between lower respiratory tract infection and development of chronic lung disease and/or death. Ureaplasma urealyticum, an organism not visible on gram stain, not recovered on routine bacteriological media, and not susceptible to antibiotics commonly used to treat neonatal infections, was the single most common organism isolated. 14% of isolates were from infants born by caesarean section with intact membranes, which indicated that infection had occurred in utero. The findings probably represented true infection of the lower respiratory tract because the organism was recovered in pure culture in numbers greater than 10(3) from 85% of the infants, and also from the blood in 26% of infants. Those infants less than or equal to 1000 g with Ureaplasma urealyticum infection of the lower respiratory tract were twice more likely to have chronic lung disease or to die than were infants of similar birth-weight but who were uninfected, or infants greater than 1000 g. Very-low-birth-weight infants infected with ureaplasmas did not differ from those uninfected, either in demographic features or in potential risk factors for chronic lung disease.

CHRONIC UREAPLASMA UREALYTICUM AND MYCOPLASMA HOMINIS INFECTIONS OF CENTRAL NERVOUS SYSTEM IN PRETERM INFANTS

In a prospective study of meningitis in 100 predominantly preterm infants, Ureaplasma urealyticum was isolated from the cerebrospinal fluid (CSF) of 8 and Mycoplasma hominis from the CSF of 5 babies undergoing investigation of suspected sepsis or treatment of hydrocephalus. U urealyticum was isolated from 6 infants with severe intraventricular haemorrhage and from 3 with hydrocephalus. In 4 babies multiple isolations were made over several weeks. There were clinical features of congenital infection with major neurological impairment in 1 infant infected with M hominis. Diagnosis is difficult because these organisms cannot be seen on gram stain and cannot readily be cultivated on routine bacteriological media, and CSF pleocytosis may be absent. This study, which used appropriate mycoplasmal media, shows that U urealyticum and M hominis are the most common microorganisms isolated from the CSF of newborn infants in a high-risk population.

In vitro susceptibilities of mycoplasmas and ureaplasmas to new macrolides and aryl-fluoroquinolones.

In vitro activities of the new macrolides clarithromycin, previously designated A-56268 (TE-031), and A-63075 and of the aryl-fluoroquinolones difloxacin (A-56619) and temafloxacin (A-62254) against 14 strains of Mycoplasma pneumoniae, 20 strains of Mycoplasma hominis, and 28 strains of Ureaplasma urealyticum were compared with that of erythromycin. All three macrolides inhibited growth of M. pneumoniae at less than 0.125 micrograms/ml. No macrolide was active against M. hominis. For five strains of U. urealyticum, MICs were greater than 256 micrograms/ml for all 3 macrolides. Excluding these, no other strain of U. urealyticum had an initial MIC of clarithromycin of greater than 1 microgram/ml, while five had initial MICs of erythromycin which were greater than 4 micrograms/ml. A-63075 was the least active of the three macrolides against ureaplasmas. Temafloxacin and difloxacin had similar activities against all three species, initially inhibiting 90% of M. pneumoniae strains at 2 and 8 micrograms/ml, 90% of M. hominis strains at 2 and 4 micrograms/ml, and 90% of U. urealyticum strains at 4 and 8 micrograms/ml, respectively. Additional pharmacokinetic and clinical trials with the new macrolides and quinolones with mycoplasmal or ureaplasmal infections are indicated.

Emergence of USA300 MRSA in a tertiary medical centre: implications for epidemiological studies

Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) has become a major pathogen, particularly in outbreaks of skin and soft-tissue infection (SSTI). A preliminary study conducted at our institution in 2004 revealed that up to 45% of inpatient and 70% of outpatient MRSA isolates tested were the USA300 genotype. In this report, we used pulsed-field gel electrophoresis (PFGE) in a retrospective analysis to determine the time when CA-MRSA USA300 moved from the community to the inpatient population. During the five-year period 2000 to 2004, unique MRSA isolates (N=253) were selected from inpatients in surgical and medical intensive care units, the general hospital population and outpatients. The most common PFGE types found in all populations from 2000 to 2003 were USA100, USA200 and USA600. USA300 was absent from all inpatients from 2000 to 2003 and only sporadic numbers found in the outpatient group. However, in 2004 the USA300 strain emerged in both outpatient and hospitalised patients. There was no difference in the distribution of USA300 between ICUs and the general inpatient population. The emergence of CA-MRSA has resulted in a shift of the MRSA strains that are implicated in healthcare-associated infections in our institution. This has been a recent development that has implications as to the use of PFGE to determine transmission of MRSA in the inpatient setting. Further evaluation of these data in the context of the epidemiology of these infections is needed to determine if more discriminatory approaches to typing will be required for monitoring the spread of the more virulent CA-MRSA phenotype within the inpatient population.

Role of Ureaplasma urealyticum in amnionitis.

Ureaplasma urealyticum is commonly isolated from the amniotic fluid of unselected individuals with intact membranes at the time of cesarean section even prior to onset of labor. The risk of placental infection increases with onset of labor, rupture of membranes and number of vaginal examinations. Qualitative cultures of women with clinical signs of intraamniotic infection and matched controls indicate that U. urealyticum can be found in 50% of amniotic fluid samples of both groups thus suggesting that it may not be a cause of clinical amnionitis. To gain further understanding of the potential role of this organism, we performed amniotic fluid and blood cultures and measured serologic responses by enzyme-linked immunosorbent assay in women with clinical intraamniotic infection and matched controls. U. urealyticum was the single most common bacterial species isolated from maternal blood and amniotic fluid but the isolation rate did not differ between symptomatic and asymptomatic women. Also other known pathogenic bacteria were often isolated from amniotic fluids containing ureaplasmas. However, the marked difference in serologic response between symptomatic and asymptomatic women and the occurrence of ureaplasmemia in some suggest that in certain individuals U. urealyticum may be a cause of clinical amnionitis. Serologic responsiveness, ureaplasmemia and isolation of ureaplasmas in pure culture from amniotic fluid of some asymptomatic women suggest that U. urealyticum may also be a cause of clinically silent amnionitis. Previous studies have shown a significant association between chorioamnionitis documented by histopathology and isolation of U. urealyticum from the placenta or infant but not the maternal cervix.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibiotic susceptibilities and therapeutic options for Ureaplasma urealyticum infections in neonates.

The appreciation of Ureaplasma urealyticum as a human pathogen and documentation of antibiotic resistance have heightened interest in drug susceptibilities and treatment alternatives for patients infected with this organism. Neonates pose special problems when therapy must be considered because of potential toxicities, clinical unfamiliarity or lack of experience. Forty-three isolates of U. urealyticum obtained from the lower respiratory tracts of neonates were tested against chloramphenicol, ciprofloxacin, clindamycin, erythromycin, doxycycline, and gentamicin by a microbroth dilution technique in 10B broth. In vitro resistance was observed in 1 or more strains for each of the drugs tested, except for erythromycin (minimal inhibitory concentration (MIC) range, 0.125 to 4 μg/ml, MIC90 = 2 μg/ml). MIC90 values for the remaining five antibiotics were: doxycycline, 2 μg/ml; chloramphenicol, 8 μg/ml; ciprofloxacin, 8 μg/ml; clindamycin, 16 μg/ml; and gentamicin, 32 μg/ml. The effect of pH and/or media components on MICs was evaluated by comparing MICs of American Type Culture Collection reference strain Staphylococcus aureus 29213 obtained in Mueller-Hinton broth (pH 7.2 to 7.4) and 10B broth (pH 6.0). No appreciable effect was detected for ciprofloxacin, chloramphenicol or doxycycline, whereas gentamicin, erythromycin and clindamycin all had MICs elevated by one to several dilutions when tested in 10B broth. In some instances the difference was sufficient to alter the interpretation of the MIC. Clinical experience in treating neonatal ureaplasmal infections is reviewed along with recommendations for obtaining cultures, initiating and monitoring efficacy of therapy.

Pathogenesis and Significance of Urogenital Mycoplasmal Infections

U. urealyticum and M. hominis can no longer be considered as harmless commensals of the lower genitourinary tract. Both can produce disease in humans. Diagnosis and management of infections due to these organisms must be based upon isolation of the organisms from the affected site and preferably the number of organisms present. Due to the frequent resistance of both organisms to tetracycline, treatment must be based upon appropriate antibiotic sensitivities. For a more detailed description of the basic biology of these organisms and isolation and identification and treatment, the reader is referred to several recent reviews.

Multiple-locus variable-number tandem-repeat analysis of meticillin-resistant Staphylococcus aureus discriminates within USA pulsed-field gel electrophoresis types *

Many isolates of meticillin-resistant Staphylococcus aureus (MRSA) are indistinguishable when compared using the standard pulsed-field gel electrophoresis (PFGE) typing method. This may present a problem when investigating local outbreaks of MRSA transmission in a healthcare setting. It also impedes investigation of the widely disseminated community-acquired MRSA (USA 300-0114) in the inpatient setting, which is displacing other traditional hospital-acquired PFGE types. Combination of methods, including multiple-locus sequence typing (MLST), spa typing and staphylococcal cassette chromosome mec (SCCmec) typing, have been used with, or in place of, PFGE to characterise MRSA for epidemiological purposes. These methods are technically challenging, time-consuming and expensive and are rarely feasible except in large laboratories in tertiary care medical centres. Another method, which is simpler and with faster turnaround time, is multiple-locus variable-number tandem-repeat analysis (MLVA). We investigated the utility of MLVA to distinguish common PFGE types. The results suggest that MLVA can be used to identify unrelated strains with identical PFGE patterns or confirm close genetic composition of linked isolates. MLVA could potentially be used in conjunction with PFGE to validate relationships, but further prospective evaluation of these relationships will be required in order to define the proper role, if any, for use of this method in hospital epidemiology.

Comparative susceptibility of Mycoplasma pneumoniae to erythromycin, ciprofloxacin, and lomefloxacin☆

Lomefloxacin was found to be comparable to ciprofloxacin in its ability to inhibit the in vitro growth of Mycoplasma pneumoniae (MIC range 2-8 mcg/ml), but it was significantly less active than erythromycin. Although 30 different strains from widely differing geographic areas and isolation time periods were examined, no macrolide-resistant strains were observed.