Inflammation and tuberculosis: host-directed therapies.

Tuberculosis (TB) is an airborne infectious disease that kills almost two million individuals every year. Multidrug-resistant (MDR) TB is caused by strains of Mycobacterium tuberculosis (M. tb) resistant to isoniazid and rifampin, the backbone of first-line antitubercular treatment. MDR TB affects an estimated 500,000 new patients annually. Genetic analysis of drug-resistant MDR-TB showed that airborne transmission of undetected and untreated strains played a major role in disease outbreaks. The need for new TB vaccines and faster diagnostics, as well as the development of new drugs, has recently been highlighted. The major problem in terms of current TB research and clinical demands is the increasing number of cases of extensively drug-resistant and 'treatment-refractory' TB. An emerging scenario of adjunct host-directed therapies is intended to target pulmonary TB where inflammatory processes can be deleterious and lead to immune exhaustion. 'Target-organ-saving' strategies may be warranted to prevent damage to infected tissues and achieve focused, clinically relevant and long-lasting anti-M. tb cellular immune responses. Candidates for such interventions may be biological agents or already approved drugs that can be 're-purposed' to interfere with biologically relevant cellular checkpoints. Here, we review current concepts of inflammation in TB disease and discuss candidate pathways for host-directed therapies to achieve better clinical outcomes.

Transposition of gram-positive transposon Tn916 in Acholeplasma laidlawii and Mycoplasma pulmonis.

Mycoplasma genetics has been limited by a lack of genetic tools such as selectable markers, methods to transfer DNA, and suitable vectors for cloning. Studies were undertaken to examine the potential of using the streptococcal transposon Tn916 as a mycoplasma genetic tool. The Escherichia coli plasmid pAM120, which contains Tn916, was transformed into Acholeplasma laidlawii and Mycoplasma pulmonis. Transposition of Tn916 into the mycoplasma chromosome apparently occurred by an excision-insertion mechanism. This example shows that newly introduced DNA from other bacteria can be successfully expressed in mycoplasma and that Tn916 should serve as a powerful genetic tool for the study of mycoplasmas.

Investigation of isoniazid and ethionamide cross-resistance by whole genome sequencing and association with poor treatment outcomes of multidrug-resistant tuberculosis patients in South Africa.

OBJECTIVE/BACKGROUND: Ethionamide (ETH) and isoniazid (INH) are part of the backbone regimen used for the treatment of multidrug-resistant tuberculosis (MDR-TB). Both ETH and INH are structurally similar and are activated by ethA and katG gene products. Resistance to INH among MDR-TB patients may cause ETH to be ineffective, as both target nicotinamide adenine dinucleotide-dependent enoyl-acyl carrier protein reductase inhA protein and mutations within inhA gene may lead to their cross-resistance. Furthermore, ETH resistance is caused by mutations within ethA and ethR genes forming part of the ETH drug activation pathway. Nicotinamide adenine dinucleotide is coded by the ndh gene, and its overexpresion may lead cross-resistance between INH and ETH drugs. Phenotypic drug susceptibility testing of ETH is difficult and often unreliable. We used whole genome sequencing to compare inhA, inhA promoter, ethA, ethR ndh, and katG genetic regions in serial isolates (baseline and follow-up) with treatment outcomes. METHODS: MDR-TB strains were collected from 46 patients before and during second-line drug treatment in KwaZulu-Natal and Eastern Cape between 2005 and 2009. All patients had phenotypically determined MDR-TB at baseline and had treatment outcomes documented. Unfavorable treatment outcomes were defined as death, default, and failure, while favorable outcomes were cure and treatment completion. Each strain had baseline and at least one strain collected on follow-up. From each strain, DNA was extracted from colonies grown on Löwenstein-Jensen slants, and fragment and jumping paired-end Illumina DNA libraries were constructed and sequenced on the Illumina HiSeq 2000 (Broad Institute, Cambridge, MA, USA). Sequences were aligned to H37Rv genome and Pilon was run to generate a list of SNPs. In silico spoligotyping was performed to a database 43 unique spacer sequences. Cross-resistance was defined as the presence of both inhA and either ethA or ethR mutations in clinical isolates. RESULTS: A total of 92 sequences from 46 serial isolates of MDR-TB patients from KwaZulu-Natal (29 isolates) and Eastern Cape (17 isolates) were analyzed. Most patients (29/46; 63.0%) had unfavorable outcomes, 13 (28.3%) had favorable outcomes, while four (8.7%) had unknown outcomes. Phylogenetic reconstruction revealed that primary genotype differed by province. The Beijing genotype was predominant in Eastern Cape, while EuroAmerican lineage (S, T, LAM, X) was found in KwaZulu-Natal. Whole genome analysis revealed nonsynonymous insertions and deletions within katG, ethA, ethR, ndh, and inhA and its promoter region. Among patients with treatment outcome data, mutations were detected in 92.8% in katG, 50% in inhA, 53.6% in ethA, 2.4% in ethR, and 19% in ndh. The majority of mutations causing ETH (20/29; 68.9%) and INH (18/29; 62.1%) resistance occurred among patients with unfavorable outcomes. Both inhA and either ethA or ethR mutations were detected in 16/29 (55.2%) patients with unfavorable outcomes. Cross-resistance of both INH and ETH drugs was associated with unfavorable treatment outcomes (p=0.021) in 16/29 (55.2%) patients compared with favorable treatment outcomes in 2/13 (15.4%) patients. CONCLUSION: Baseline ETH molecular resistance before second-line treatment is a concern. Unfavorable treatment outcomes of patients with ethA, ethR, and inhA mutations highlight the importance of genotypic testing before initiation of treatment containing ETH. The clinical significance of whole genome analysis for early detection of mutations predictive of treatment failure needs further investigation.

Dissection of bacteriophage lambda site-specific recombination using synthetic peptide combinatorial libraries.

A wide variety of tools have been used to dissect biochemical pathways, inhibitors being chief among them. Combinatorial approaches have made the search for inhibitors much more efficient. We have applied such an approach to identify hexapeptides which inhibit different steps in a site-specific recombination reaction mediated by the bacteriophage lambda integrase protein. Integrase's mechanism is still incompletely understood, in large part because several pathway intermediates remain hard to isolate. Integrase-catalyzed recombination is very efficient, but if blocked, it is highly reversible to substrates; this combination makes some intermediates exceedingly transient. We have used synthetic peptide combinatorial libraries to screen for hexapeptides that affect the recombination pathway at different stages, and have identified two families of peptides: one probably blocks DNA cleavage, the other may stabilize the Holliday junction intermediates. These peptides do not resemble parts of integrase or any of the other helper functions in the pathway. The deconvolution of hexapeptide libraries based both on inhibition of an enzymatic reaction as well as on accumulation of reaction intermediates is a novel approach to finding useful tools for dissecting a biochemical pathway.

Peptide inhibitors of DNA cleavage by tyrosine recombinases and topoisomerases.

The study of biochemical pathways requires the isolation and characterization of each and every intermediate in the pathway. For the site-specific recombination reactions catalyzed by the bacteriophage lambda tyrosine recombinase integrase (Int), this has been difficult because of the high level of efficiency of the reaction, the highly reversible nature of certain reaction steps, and the lack of requirements for high-energy cofactors or metals. By screening synthetic peptide combinatorial libraries, we have identified two related hexapeptides, KWWCRW and KWWWRW, that block the strand-cleavage activity of Int but not the assembly of higher-order intermediates. Although the peptides bind DNA, their inhibitory activity appears to be more specifically targeted to the Int-substrate complex, insofar as inhibition is resistant to high levels of non-specific competitor DNA and the peptides have higher levels of affinity for the Int-DNA substrate complex than for DNA alone. The peptides inhibit the four pathways of Int-mediated recombination with different potencies, suggesting that the interactions of the Int enzyme with its DNA substrates differs among pathways. The KWWCRW and KWWWRW peptides also inhibit vaccinia virus topoisomerase, a type IB enzyme, which is mechanistically and structurally related to Int. The peptides differentially affect the forward and reverse DNA transesterification steps of the vaccinia topoisomerase. They block formation of the covalent vaccinia topoisomerase-DNA intermediate, but have no apparent effect on DNA religation by preformed covalent complexes. The peptides also inhibit Escherichia coli topoisomerase I, a type IA enzyme. Finally, the peptides inhibit the bacteriophage T4 type II topoisomerase and several restriction enzymes with 2000-fold lower potency than they inhibit integrase in the bent-L pathway.

Community-based care vs. centralised hospitalisation for MDR-TB patients, KwaZulu-Natal, South Africa.

SETTING: KwaZulu-Natal, South Africa, a predominantly rural province with a high burden of tuberculosis (TB), multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine the most effective care model by comparing MDR-TB treatment outcomes at community-based sites with traditional care at a central, specialised hospital. DESIGN: A non-randomised observational prospective cohort study comparing community-based and centralised care. Patients at community-based sites were closer to home and had easier access to care, and home-based care was available from treatment initiation. RESULTS: Four community-based sites treated 736 patients, while 813 were treated at the centralised hospital (total = 1549 patients). Overall, 75% were HIV co-infected (community: 76% vs. hospitalised: 73%, P = 0.45) and 86% received antiretroviral therapy (community: 91% vs. hospitalised: 82%, P = 0.22). On multivariate analysis, MDR-TB patients were more likely to have a successful treatment outcome if they were treated at a community-based site (adjusted OR 1.43, P = 0.01). However, outcomes at the four community-based sites were heterogeneous, with Site 1 demonstrating that home-based care was associated with an increased treatment success of 72% compared with success rates of 52-60% at the other three sites. CONCLUSION: Community-based care for MDR-TB patients was more effective than care in a central, specialised hospital. Home-based care further increased treatment success.

Extragenital Mycoplasma hominis infections in adults.

PURPOSE: To heighten awareness of the role of Mycoplasma hominis as an extragenital pathogen in adults. PATIENTS AND METHODS AND RESULTS: Patients ranged in age from 14 to 76 years. Thirteen patients were immunosuppressed, including nine organ transplant recipients; three were receiving steroids, and two had an underlying malignancy. The remainder were immunocompetent. Thirteen patients had prior surgery at or near the site of infection. M. hominis was isolated from normally sterile sites such as blood or cerebrospinal, pleural, abdominal and joint fluids, and bone. Non-sterile sites of isolation included surgical wounds and pulmonary secretions. The organism was detected in anaerobic cultures of clinical specimens sent to the laboratory for routine bacteriologic culture. Gram stains of fluids or wound drainage revealed neutrophils but no bacteria. Anti-mycoplasmal therapy was effective in eradicating the organism in 13 of 15 patients who were treated. Of those in whom treatment failed, one patient had an antibiotic-resistant isolate and the other had M. hominis isolated from the lung at postmortem after just 2 days of therapy. CONCLUSION: Our experience suggests that significant infections due to M. hominis, although uncommon, are not rare, and methods to isolate and identify this organism should be available for general adult medical and surgical populations.

Ureaplasmal pneumonia and sepsis associated with persistent pulmonary hypertension of the newborn.

Ureaplasma urealyticum was isolated from the lower respiratory tract of three infants with persistent pulmonary hypertension of the newborn. In one, cultures positive for U urealyticum were obtained on multiple occasions from trachea, blood, and pleural fluid prior to the infant's death on postnatal day 6. Autopsy findings confirmed the presence of severe pneumonia and the organism was again recovered from multiple sites. A second infant had no apparent predisposing factors for development of persistent pulmonary hypertension of the newborn but U urealyticum and Staphylococcus epidermidis were recovered from the trachea antemortem and from lung tissue obtained during autopsy on the 12th postnatal day. The third infant had persistent pulmonary hypertension of the newborn and a pulmonary infiltrate within hours after birth with tracheal cultures positive for both U urealyticum and Mycoplasma hominis. Erythromycin was given for ten days, and the infant gradually improved. Prolonged ventilation with supplemental oxygen was necessary, and chronic lung disease developed. This is the first report of neonatal ureaplasmal pneumonia with sepsis and persistent pulmonary hypertension of the newborn as well as the first time a microorganism other than streptococci has been specifically implicated in the pathogenesis of persistent pulmonary hypertension of the newborn. Respiratory infections with U urealyticum or other bacteria should be considered as possible causative or contributory factors in infants with persistent pulmonary hypertension of the newborn.

Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: follow-up.

A total of 205 infants who were hospitalized when younger than 3 months of age for pneumonitis were followed longitudinally. Of these patients, 145 (70%) had evidence of infection with one or more pathogens. The most common etiologic agents were Chlamydia trachomatis 61/193 (36%), respiratory syncytial virus 33/142 (23%), cytomegalovirus 42/203 (20%), Pneumocystis carinii 30/171 (17%), and Ureaplasma urealyticum 21/125 (16%). The initial clinical presentation was characterized by cough, rales, normal temperature, and diffuse obstructive airways disease by chest roentgenogram. Regardless of etiology, significant association occurred for cough and cytomegalovirus, apnea and Pneumocystis, and conjunctivitis and Chlamydia. Longitudinal follow-up demonstrates a mortality of 7/205 (3.4%). Morbidity was manifest as recurrent wheezing episodes in 86/187 (46%) patients, persistently abnormal chest roentgenographic findings for at least 12 months in 17/109 (15%) patients, and abnormal pulmonary functions in 15/25 (60%) patients. These abnormalities occurred irrespective of prematurity, atopy, or the initial etiologic agent associated with the pneumonitis. These data add further evidence that respiratory infections during infancy may well be predecessors of obstructive airways disease in later life.

Association of genital mycoplasmas with exudative vaginitis in a 10 year old: a case of misdiagnosis.

A 10-year-old girl with a 1-year history of lower genitourinary tract symptoms suggestive of bacterial infection but with numerous negative urine cultures was referred to the University of Alabama urology clinic after empirical treatment with multiple antibiotics failed to resolve her symptoms. An extensive urologic evaluation revealed no structural or physiologic abnormalities, but an exudative vaginitis was noted and large numbers of Ureaplasma urealyticum and Mycoplasma hominis were isolated from the lower genital tract. Cultures for Chlamydia, viruses, and routine bacterial pathogens were negative. After initiation of tetracycline therapy, symptoms resolved and subsequent cultures for mycoplasmas were negative. In addition, a seroconversion was noted for M hominis but not for U urealyticum. Chlamydia serology was negative. It was later learned that the patient had been sexually molested just prior to the onset of symptoms. This case illustrates the necessity of early consideration of a mycoplasmal etiology in the patient with persistent genitourinary symptoms and no obvious bacterial pathogen, or in the patient whose condition is refractory to routine antibiotic therapy.

Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: a prospective study.

In a prospective study of 104 infants between 1 and 3 months of age hospitalized with pneumonitis, 65 (63%) had evidence of infection with one or more potential respiratory pathogens. Single infections were noted in 48 (74%) whereas mixed infections occurred in 17 (26%) of 65 infected infants. The four most common infections were Chlamydia trachomatis (15/59, 25%), Ureaplasma urealyticum (8/38, 21%), cytomegalovirus (21/104, 20%), and Pneumocystis carinii (19/104, 18%). In sharp contrast, the incidence of these infections in control infants was 0% (0/25), 4% (2/49), 3% (3/97), and 0% (0/64), respectively. The clinical, radiologic, and laboratory characteristics of the pneumonitis syndrome associated with Chlamydia, cytomegalovirus, and Pneumocystis were indistinguishable from each other. Patients with mixed infections had a more severe pneumonitis as measured by the occurrence of apnea and the need of oxygen therapy an mechanical ventilation. The patients enrolled in this study are being followed-up to determine the longitudinal course of these infections.

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 micrograms/ml, MIC90 = 2 micrograms/ml). MIC90 values for the remaining five antibiotics were: doxycycline, 2 micrograms/ml; chloramphenicol, 8 micrograms/ml; ciprofloxacin, 8 micrograms/ml; clindamycin, 16 micrograms/ml; and gentamicin, 32 micrograms/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.

Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate.

We evaluated 260 previously healthy children ages 3 through 12 years who had clinical signs and symptoms of pneumonia, radiographically confirmed. Patients were randomized 1:1 to a 10-day course of either clarithromycin suspension 15 mg/kg/day divided twice a day or erythromycin suspension 40 mg/kg/day divided twice a day or three times a day. Evidence of infection with Chlamydia pneumoniae was detected in 28% (74) of patients: 13% (34) by nasopharyngeal culture and 18% (48) by serology with the microimmunofluorescence assay. Evidence of infection with Mycoplasma pneumoniae was detected in 27% (69) of patients: 20% (53) by nasopharyngeal culture or polymerase chain reaction and 17% (44) by serology with the use of enzyme-linked immunosorbent assay. Serologic confirmation of infection was observed in 23% (8) and 53% (28) of patients with bacteriologically detected C. pneumoniae and M. pneumoniae, respectively. Treatment with clarithromycin vs. erythromycin, respectively, yielded the following outcomes: clinical success 98% (121 of 124) vs. 95% (105 of 110); radiologic success 98% (109 of 111) vs. 94% (92 of 110); and eradication by pathogen, C. pneumoniae 79% (15 of 19) vs. 86% (12 of 14) and M. pneumoniae 100% (9 of 9) vs. 100% (4 of 4). Adverse events were primarily gastrointestinal occurring in almost one-fourth of patients in both groups, and were mild to moderate in severity. Clarithromycin and erythromycin were similarly effective and safe for the treatment of radiographically proved, community-acquired pneumonia in children older than 2 years old.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children.

OBJECTIVE: To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. METHODS: Multicenter, parallel group, double blind trial in which patients 6 months to 16 years of age with community-acquired pneumonia were randomized 2:1 to receive either azithromycin for 5 days or conventional therapy for 10 days (amoxicillin/clavulanate if < or =5 years of age or erythromycin estolate if >5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy. RESULTS: Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05). CONCLUSION: Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.

Neonatal serologic response at term to the genital mycoplasmas.

Genital mycoplasmas are frequently found in the amniotic fluid (AF) of women with ruptured membranes but are infrequent pathogens in the neonates born to these women. The serologic response to the genital mycoplasmas, Mycoplasma hominis and Ureaplasma urealyticum, was studied in 35 mother-baby pairs following term deliveries. Amniotic fluid and neonatal surface cultures were obtained in all cases, as were maternal and neonatal acute and convalescent sera. Despite significant maternal serologic response, there was essentially no neonatal response. Mothers with M. hominis in the AF were significantly more likely than those with negative cultures for M. hominis to exhibit IgG seroconversion and had significantly greater changes in IgG concentrations. Their infants, however, did not exhibit a significant seroresponse regardless of the AF and neonatal culture results. There was also a significant maternal seroresponse to U. urealyticum. However, this did not correlate with the presence of U. urealyticum in the AF. Significantly fewer neonates exhibited a seroresponse to U. urealyticum, again with no relation to culture results.

Role of Ureaplasma urealyticum and other pathogens in the development of chronic lung disease of prematurity.

A prospective cohort study enrolling 107 infants weighing less than 1250 g was conducted between September 1, 1986, and November 15, 1987 in order to determine the role of microorganisms on the development of chronic lung disease (CLD). Ureaplasma urealyticum was isolated significantly more frequently from gastric aspirates and nasopharyngeal or endotracheal aspirates from 43 infants developing CLD than from 56 who did not (51% vs. 16%; P less than 0.005). Infants developing CLD, defined by radiographic and blood gas abnormalities, were significantly younger (26 vs. 29 weeks; P less than 0.0001), weighed significantly less (830 vs. 1050 g; P less than 0.0001) and required more ventilatory support (37 vs. 10 were being ventilated and 42 vs. 26 received oxygen supplementation on Day 7) compared with those who did not develop CLD. Viruses were isolated in association with U. urealyticum in two infants developing CLD and in one infant who did not develop CLD. Mycoplasma hominis was isolated from three infants who were colonized with U. urealyticum and developed CLD. Chlamydia trachomatis was not recovered from any patients. From a discriminant analysis it was found that U. urealyticum contributed to the development of CLD along with the effect of ventilatory support, gestational age and severity of initial respiratory disease. The effect of interventions directed against U. urealyticum on the development of CLD deserves further study.

Serum concentrations of erythromycin after intravenous infusion in preterm neonates treated for Ureaplasma urealyticum infection.

Erythromycin is receiving renewed attention as an alternative for treatment of neonatal infections caused by Ureaplasma urealyticum because of recently proved abilities of this organism to produce systemic disease in this population. Although erythromycin has been used clinically for almost 40 years, very little is known about its activity in the preterm neonate. Fourteen neonates, birth weights < or = 1500 g and < or = 15 days of age, from whom U. urealyticum was isolated from the lower respiratory tract were randomized to receive erythromycin lactobionate either 25 or 40 mg/kg/day in four divided doses at 6-hour intervals scheduled for a total of 10 days. Blood samples collected at multiple time points after initial and steady state doses were assayed for erythromycin by liquid chromatography. Minimal inhibitory concentrations (MICs) of erythromycin for the U. urealyticum isolates were determined. MICs ranged from 0.031 to 2 micrograms/ml; MIC90 = 2 micrograms/ml. Serum erythromycin concentrations met or exceeded most MICs, with peak values of 3.05 to 3.69 and 1.92 to 2.9 micrograms/ml for the 40- and 25-mg/kg/day dosage groups, respectively. Pharmacokinetic parameters were calculated after the initial dose and at steady state for both dosage groups and compared. No adverse effects thought to be related to administration of erythromycin were observed. These preliminary findings showed that erythromycin is well-tolerated, has favorable pharmacokinetic activity in the preterm neonate and should be further investigated for treatment of ureaplasmal infections.

Mycoplasmal infections of cerebrospinal fluid in newborn infants from a community hospital population.

Mycoplasma hominis or Ureaplasma urealyticum have previously been isolated from cerebrospinal fluid (CSF) in 13 of 100 newborn infants tested from a high risk university hospital population where the mothers were of predominantly lower income and socioeconomic status and had often received little or no prenatal care. We sought to determine whether such infections occur in neonates born to women cared for mainly through private obstetric practices and who delivered in 4 suburban community hospitals. CSF cultures were done in 318 infants during an 8-month period. M. hominis was isolated from 9 and U. urealyticum from 5 CSF cultures. Four infants infected with U. urealyticum and 3 infected with M. hominis were born at term. One infant infected with U. urealyticum had a birth weight of less than 1000 g. In 5 infants clearance of the infecting organism was documented without specific treatment. Twelve infants had good perinatal outcomes regardless of treatment and 2 died. One death in a 2240-g infant infected with M. hominis was associated with Haemophilus influenzae sepsis and pneumonia. The other death occurred 3 days after birth in a 630-g infant infected with U. urealyticum who had evidence of meningitis and intraventricular hemorrhage. Results of this study suggest that mycoplasmas are common causes of neonatal CSF infections, not only in high risk populations, but also in the general population.

Association of post-cesarean delivery endometritis with colonization of the chorioamnion by Ureaplasma urealyticum.

OBJECTIVE: To determine if asymptomatic antenatal colonization of the chorioamnion with Ureaplasma urealyticum is a risk factor for the development of post-cesarean delivery endometritis. METHODS: The chorioamnion was cultured at cesarean delivery for aerobic and anaerobic bacteria, mycoplasmas, Chlamydia trachomatis, and Trichomonas vaginalis in 575 singleton gestations with intact membranes. Culture results were compared with the clinical outcome. Postoperative endometritis was defined as a temperature of 38C with uterine tenderness and without other nonpelvic sources of fever. RESULTS: Fifty-eight (10%) of the 575 women developed endometritis. Women with spontaneous labor developed endometritis twice as often as those delivered for medical or obstetric indications (17 versus 8%, P = .002). Endometritis occurred in 28% of women with U urealyticum present in the chorioamnion at cesarean delivery, compared with only 8.4% if the culture was negative and 8.8% if only bacteria other than U urealyticum were isolated (P < .001). Gestational age less than 34 weeks, spontaneous labor, and a vertical uterine incision were all associated with endometritis (P < or = .002). Regression analysis controlling for gestational age and incision type revealed a threefold increased risk of endometritis if the chorioamnion was colonized with U urealyticum at cesarean (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.1-8.3) and an eightfold risk (OR 7.7, 95% CI 1.9-31.5) in women in whom the onset of labor was spontaneous. CONCLUSION: Colonization of the chorioamnion with U urealyticum in women with intact membranes being delivered by cesarean is a significant, independent predictor of subsequent endometritis.

Mycoplasma hominis septic thrombophlebitis in a patient with multiple trauma: a case report and literature review.

Mycoplasma hominis was recovered from the site of a septic thrombophlebitis on the left cephalic veins of a patient with pelvic and other multiple trauma. The organisms were initially isolated from routine cultures in conventional blood agar media incubated anaerobically. The absence of other demonstrable pathogens and the patient's serologic response to the isolate support the role of the organism as the cause of this previously unreported mycoplasmal infection. M. hominis should be considered a possible cause of sepsis in selected cases of infections following pelvic trauma or manipulations of the genitourinary tract.