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Background: Stenotrophomonas maltophilia is a multi-drug-resistant, hospital-acquired Gram-negative bacillus associated with significant morbidity and mortality. The objective of this study is to identify risk factors and outcomes associated with S. maltophilia isolation in a high-risk neonatal population., Methods: This was a retrospective matched case-control study. Cases were matched 1:2 for years of neonatal intensive care unit admission, completed weeks' gestational age and birth weight in 250-gram incremental categories., Results: A total of 15 cases and 35 controls were included in the analyses. Risk factors for S. maltophilia isolation included days of antibiotics (24 vs. 18, P = 0.036), days of broad-spectrum antibiotics (19 vs. 12 days, P = 0.027), days of meropenem (9 vs. 6 days, P = 0.018) and any meropenem exposure (100% vs. 22%, P = 0.005). Other risk factors were any corticosteroid exposure (66.7% vs. 20%, P = 0.001), days of total parenteral nutrition (55 vs. 31 days, P = 0.017) and days of invasive mechanical ventilation (28 vs. 7, P = 0.015). S. maltophilia isolation was associated with increased length of neonatal intensive care unit stay (134 vs. 69 days, P < 0.001) and mortality (33.3% vs. 0%, P = 0.001)., Conclusions: Antibiotic stewardship efforts should be made to decrease the risk of S. maltophilia isolation and associated mortality. Carbapenem over-use should be specifically addressed with institutional policies and unit-based guidelines. Additional neonatal studies are needed to confirm these findings and explore other possible risk factors., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The rise in antibiotic resistance to N. gonorrhoeae poses a substantial threat to effective gonorrhea treatment. Historical progression of resistance from sulfonamides to the more recent declines in efficacy of fluoroquinolones and susceptibilities of ceftriaxone highlight the urgent need for novel therapeutic approaches, necessitating the examination of alternative and new antibiotics., Areas Covered: This review examines the potential of repurposing older antibiotics for gonorrhea treatment with a focus on their efficacy and limitations. These include aztreonam, ertapenem, and fosfomycin. New oral drugs zoliflodacin and gepotidacin are in late clinical development, but there are concerns regarding their effectiveness for extragenital infections and the development of resistance., Expert Opinion: While ceftriaxone remains the best treatment for gonorrhea across all anatomic sites, resistance may eventually limit its use. Among older antibiotics, ertapenem shows the most potential as an alternative but shares the same administrative drawbacks as ceftriaxone. New oral drugs zoliflodacin and gepotidacin initially appeared promising, but their efficacy for pharyngeal infections and potential for resistance development are concerning. Phase 3 trial results have not been made available except through press releases, which perpetuates concerns. Understanding pharmacokinetic and pharmacodynamic profiles of antibiotics will be key in optimizing future treatment recommendations.

Introduction: Neonatal ocular prophylaxis with 0.5% erythromycin ophthalmic ointment is mandated by law in many U.S. states despite its lack of efficacy in preventing chlamydial ophthalmia and the low incidence of gonococcal ophthalmia today. The current shortage of 0.5% erythromycin ophthalmic ointment is bringing into question what alternatives exist for neonatal ocular prophylaxis for the prevention of gonococcal ophthalmia. Providers in states with mandates are concerned with the implications of administering intramuscular ceftriaxone to every newborn. Azithromycin eye drops are being considered as an alternative., Areas Covered: This article discusses 1% azithromycin eye drops as an alternative to 0.5% erythromycin ophthalmic ointment. Clinical experience, side effects, resistance, logistics, pharmacokinetics, and pharmacodynamics are considered., Expert Opinion: Azithromycin eye drops are not an appropriate alternative to 0.5% erythromycin ophthalmic ointment for ocular prophylaxis. Prenatal screening and treatment of pregnant women is the most effective way to prevent neonatal ophthalmia. Mandates for universal prophylaxis should be withdrawn to avoid unnecessary medication administration, healthcare costs, and potential harm.

Introduction: Cefotaxime has been used for the management of neonatal infections since the 1990s for suspected meningitis and to mitigate gentamicin-associated renal injury. Its shortage in 2015 and subsequent removal from the U.S. pharmaceutical market forced providers to consider alternatives. Ceftriaxone, a cephalosporin with an identical antibacterial spectrum of activity to cefotaxime, is contraindicated in neonates due to its risk of biliary pseudolithiasis. Ceftazidime was recommended as an alternative by the American Academy of Pediatrics but is inequivalent., Areas Covered: This article addresses indications for cephalosporin use and considerations when selecting an alternative to cefotaxime. Differences among cefotaxime, ceftriaxone, ceftazidime, and cefepime are discussed and compared to the standard-of-care presumptive regimen, ampicillin, and gentamicin. The authors consider the data behind the neonatal contraindication to ceftriaxone and provide recommendations for their application to practice., Expert Opinion: The data against ceftriaxone use in neonates remain poor, particularly in the context of the cefotaxime shortage and lack of an equivalent alternative. Ceftriaxone could be considered in low-risk neonates without hyperbilirubinemia or exposure to calcium-containing fluids on a case-by-case basis. Ceftazidime monotherapy for presumptive management of neonatal infections is inappropriate; cefepime should be more frequently utilized in neonates who are poor candidates for ceftriaxone.

Introduction: Azithromycin was recommended as the first-line therapeutic regimen for treatment of genital infections in men and women by the Centers for Disease Control in 1998. A series of studies of azithromycin for treatment of rectal chlamydial infection in men who have sex with men (MSM) found that azithromycin was significantly less effective than doxycycline., Areas Covered: Literature on treatment of rectal C. trachomatis from 2000 through May 2020 was searched using PubMed. Retrospective and observational studies were identified documenting the frequency and treatment of rectal chlamydial infection in MSM, heterosexual men and women that reported lower efficacy of single-dose azithromycin compared to doxycycline. Literature on possible reasons for the lower efficacy were also reviewed including studies of antibiotic resistance, impact of organism load, and persistent infection in rectal specimens and pharmacokinetics and pharmacodynamics of azithromycin in rectal tissue., Expert Opinion: The available data suggests that single-dose azithromycin is not as effective as azithromycin for the treatment of rectal infection in MSM and women. Most of these data have been retrospective or from observational studies. Final recommendations will depend on the outcome of prospective, randomized, treatment studies. We may also need to examine other dosage regimens for azithromycin.

Background: Neonatal ocular prophylaxis with silver nitrate does not prevent neonatal conjunctivitis due to Chlamydia trachomatis. The efficacy of antibiotic containing preparations for prevention of neonatal chlamydial conjunctivitis (NCC) has not been established., Objective: To examine published literature to determine whether antibiotic containing preparation are efficacious for prevention of NCC and C. trachomatis in the nasopharynx., Methods: A literature search of MEDLINE and EMBASE. Articles were selected for review if their content included 4 key criteria: (1) Prospective/comparative study. (2) Prenatal screening of mothers for C. trachomatis with results reported. (3) Follow-up of infants born to chlamydia-positive women. (4) Infants prospectively followed at regular intervals and tested for C. trachomatis in the eye/ nasopharynx (NP)., Results: The search yielded 159 studies; 11 were selected for full reviews, eight were excluded; three addressed the four criteria. Rates of C. trachomatis conjunctivitis in infants in included studies who received silver nitrate was 20-33%; positive NP, 1-28% and pneumonia, 3-8%. Rates of C. trachomatis conjunctivitis in neonates who received erythromycin or tetracycline prophylaxis did not differ from silver nitrate; 0-15 and 11%, respectively, who received erythromycin or tetracycline developed NCC. Similarly, 4-33 and 5% of infants who received erythromycin or tetracycline, respectively, had positive NP cultures; 0-4% developed chlamydial pneumonia., Conclusion: Neonatal ocular prophylaxis with erythromycin or tetracycline ophthalmic ointments does not reduce incidence of neonatal chlamydial conjunctivitis or respiratory infection in infants born to mothers with C. trachomatis infection compared to silver nitrate.

The in vitro activities of omadacycline, azithromycin, doxycycline, moxifloxacin, and levofloxacin were tested against 15 isolates of Chlamydia pneumoniae The minimum inhibitory concentration at which 90% of the isolates of C. pneumoniae were inhibited by omadacycline was 0.25 μg/ml (range, 0.03 to 0.5 μg/ml)., (Copyright © 2019 American Society for Microbiology.)

Background: Vancomycin is the preferred drug for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in children. In adults, treatment failure with vancomycin has been associated with an area under the curve/24 hrs /MIC (AUC24/MIC) ratio of ≤400 and high minimum inhibitory concentrations (MIC ≥1.0 mg/L). Vancomycin dosing information to ensure optimal AUC24/MIC in the pediatric population remains limited., Methods: A retrospective chart review from August 2008 to 2011 and a prospective study from September 2011 to October 2013 was conducted on all pediatric patients at two hospitals in Brooklyn, NY with positive cultures for MRSA who received vancomycin. Treatment failure was defined as persistent positive cultures (≥5 days) or persistence of clinical symptoms. Vancomycin AUC24/MICs were calculated., Results: Twenty-three children with MRSA infection, 0-18 years of age, were identified; 18 of 23 (78.3%) were community acquired. MICs of 91% of the isolates were ≥1.5 µg/mL and 9 had MICs of 2 µg/mL. Treatment failure was seen in 12 (52%) patients with MICs of 1.5 µg/mL and above. Vancomycin trough levels >15 µg/mL and AUC24/MIC >400 were achieved in only 18% and 0% of patients, respectively., Conclusions: High treatment failure rates with vancomycin was associated with MIC ≥1.5 µg/mL. Current recommended vancomycin dosing in children did not achieve a trough concentration of >15 µg/mL in majority of the patients and none achieved an AUC24/MIC>400.

Persistent respiratory infections caused by Chlamydia pneumoniae have been implicated in the pathogenesis of chronic diseases (e.g. asthma). Antibiotics are used to treat C. pneumoniae respiratory infections; however, the use of antibiotics as anti-inflammatory agents in treatment of asthma remains controversial. The current study investigated whether ciprofloxacin, azithromycin, or doxycycline can suppress C. pneumoniae-induced production of immunoglobulin (Ig) E or cytokines in peripheral blood mononuclear cells (PBMC) obtained from asthmatic children. Apart from blood, nasopharyngeal swab specimens were also collected to test for the presence of C. pneumoniae and/or M. pneumoniae (qPCR). PBMC (1.5 x 10 6 ) from asthmatic pediatric patients (N = 18) were infected or mock infected for 1 h ± C. pneumoniae AR-39 at a multiplicity of infection (MOI) = 0.1, and cultured ± ciprofloxacin, azithromycin, or doxycycline (0.1 or 1.0 μg/mLmL) for either 48 h (cytokines) or 10 days (IgE). Interleukin (IL)-4, interferon (IFN)-γ and IgE levels in supernatants were measured (ELISA). When PBMC were infected with C. pneumoniae, IL-4 and IFNγ production increased (p = 0.06 and 0.03, respectively); IgE levels were low. The now-elevated levels of IL-4 didn't decrease significantly after addition of ciprofloxacin, azithromycin, or doxycycline. However, infected PBMC IFNγ formation decreased significantly when 0.1 μg/mL doxycycline was employed (p = 0.04); no dose of ciprofloxacin or azithromycin had any impact. This inhibitory outcome with doxycycline lends support to the use of tetracyclines as immune modulators and anti-inflammatory medications in treatment of C. pneumoniae-infected asthma patients., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Chlamydiae are obligate intracellular bacterial pathogens whose entry into mucosal epithelial cells is required for intracellular survival and subsequent growth. The life cycle of Chlamydia spp. and the ability to cause persistent, often subclinical infection, has major ramifications for diagnosis and treatment of Chlamydia trachomatis and C. pneumoniae infections in humans., Areas Covered: This paper reviews the current literature on the antimicrobial susceptibilities and treatment of genital infections due to C. trachomatis and respiratory infections due to C. pneumoniae published since 2011., Expert Opinion: Chlamydiae are susceptible to antibiotics that interfere with DNA and protein synthesis, including tetracyclines, macrolides and quinolones, which are the compounds that have been most extensively studied and used for treatment of human infection. Since our original review was published in 2011, there have been some major advances in diagnostic tests for C. trachomatis and the introduction of the first FDA-approved test for the detection of C. pneumoniae in respiratory samples. However, the options for treating chlamydial infections have largely remained the same. There are a small number of new drugs currently in preclinical development and early clinical trials that may have a role in the treatment of chlamydial infections.

The in vitro activities of AZD0914, levofloxacin, azithromycin, and doxycycline against 10 isolates each of Chlamydia trachomatis and Chlamydia pneumoniae were tested. For AZD0914, the MIC90s for C. trachomatis and C. pneumoniae were 0.25 μg/ml (range, 0.06 to 0.5 μg/ml) and 1 μg/ml (range, 0.25 to 1 μg/ml), respectively, and the minimal bactericidal concentrations at which 90% of the isolates were killed (MBC90s) were 0.5 μg/ml for C. trachomatis (range, 0.125 to 1 μg/ml) and 2 μg/ml for C. pneumoniae (range, 0.5 to 2 μg/ml)., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

The in vitro activities of nemonoxacin, levofloxacin, azithromycin, and doxycycline were tested against 10 isolates each of Chlamydia trachomatis and Chlamydia pneumoniae. The MICs at which 90% of the isolates of both C. trachomatis and C. pneumoniae were inhibited (MIC90s) were 0.06 μg/ml (range, 0.03 to 0.13 μg/ml). The minimal bactericidal concentrations at which 90% of the isolates were killed by nemonoxacin (MBC90s) were 0.06 μg/ml for C. trachomatis (range, 0.03 to 0.125 μg/ml) and 0.25 for C. pneumoniae (range, 0.015 to 0.5 μg/ml).

Objectives: Chlamydia pneumoniae, an obligate intracellular bacterium, has been associated with asthma and the induction of immunoglobulin E (IgE) responses. Whereas tetracyclines have anti-chlamydial activity, their effect on human IgE responses to C. pneumoniae has not been studied., Methods: Peripheral blood mononuclear cells (PBMCs) from serum IgE+ allergic asthmatic subjects (n = 11) and healthy controls (n = 12) were infected with C. pneumoniae and cultured for 12 days with or without doxycycline (0.01-1.0 mg/L). IgE, interferon (IFN)-γ and interleukin (IL)-4 levels in supernatants were determined on days 1-12 post-infection, and C. pneumoniae DNA copy numbers in PBMC culture were measured on day 2 (quantitative PCR)., Results: C. pneumoniae-infected PBMCs from allergic asthmatic individuals had increased levels of IgE in supernatants compared with uninfected PBMCs (520% on day 10 post-infection, P = 0.008). IgE levels in PBMC cultures from controls were undetectable (<0.3 ng/mL). Increases in C. pneumoniae-induced IgE in asthmatics correlated with those of C. pneumoniae-induced IL-4 (r = 0.98; P < 0.001), but not with IFN-γ. The addition of doxycycline (1.0 mg/L) to the culture strongly suppressed the production of IgE (>70%, P = 0.04) and IL-4 (75%, P = 0.018), but not IFN-γ. The suppressive effect on IL-4 production remained significant even at concentrations of doxycycline that were subinhibitory (0.01 mg/L) for C. pneumoniae. In both asthmatic participants and controls, no significant effect of doxycycline on DNA copy numbers of C. pneumoniae was observed., Conclusions: Doxycycline suppressed the C. pneumoniae-induced production of IgE and IL-4, but not IFN-γ, in PBMCs from IgE+ allergic asthmatic subjects. These findings resulted from the immunomodulatory anti-allergic properties of tetracyclines.

In this study, we report 4 infants who developed severe ocular reactions after neonatal ocular prophylaxis with gentamicin ophthalmic ointment during a period of erythromycin ophthalmic ointment shortage. In light of this experience, gentamicin ophthalmic ointment should not be used as an alternative for neonatal ocular prophylaxis.

The in vitro activities of CEM-101, telithromycin, azithromycin, clarithromycin, and doxycycline against 10 isolates each of Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae were tested. The MIC at which 90% of the isolates of both C. trachomatis and C. pneumoniae were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by CEM-101 were 0.25 microg/ml (ranges, 0.125 to 0.5 microg/ml for C. trachomatis and 0.25 to 1.0 microg/ml for C. pneumoniae).

Sophorolipids (SLs), glycolipids produced by yeasts, have been reported to have immunomodulating activity and to reduce the mortality rate in animal models of sepsis. In the present study, the antibacterial activities of SLs and several derivatives were tested against a selection of standard bacterial isolates using the broth microdilution method. The SL derivatives tested did not show any significant antibacterial activity in vitro when tested at clinically relevant concentrations. Most likely the reported decrease of mortality rate in the rat septic shock model was not secondary to antibacterial activity of SLs. The SLs may be used as anti-inflammatory agents or immunomodulators without affecting the host's bacterial flora.

Background: The ketolides are a subclass of macrolides, which were designed specifically to overcome macrolide-resistant respiratory pathogens. Ketolides lack the cladinose sugar, which is replaced with a 3-ketone group. Ketolides bind to a secondary region on domain II of the 23S rRNA subunit. Telithromycin was the first ketolide to be approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and sinusitis. However, in 2006, after reports of serious hepatotoxicity, the FDA issued a public health advisory followed by a warning. In 2007 the indications for treatment of AECB and sinusitis were removed from the labeling. Cethromycin (ABT-773) is the only other ketolide currently under clinical development., Objective: To review currently available data on cethromycin, including chemistry, in vitro activity, pharmacokinetics, pharmacodynamics, in vivo activity and results of treatment studies in humans., Methods: A search was made in PubMed, pharmaceutical databases and meeting abstracts using the terms ketolides, ABT-773 and cethromycin., Results/conclusions: Cethromycin has comparable tissue penetration, pharmacokinetics and in vitro activity compared with telithromycin to Streptococcus pneumoniae, including multidrug-resistant isolates, Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. There is only one published CAP treatment study that compared cethromycin 150 mg q.d. with 150 mg b.i.d. One Phase II and a Phase II/III study have been presented in abstract form, both were non-comparative, dose-ranging studies, which suggested that 150 mg q.d. or 300 mg q.d. were comparable in terms of clinical response and bacterial eradication, although data on the latter are limited. Data on side effects are limited and appear to be mainly gastrointestinal. There have been no reports of serious hepatotoxicity at the time of this writing. Cethromycin may have other uses in addition to treatment of CAP respiratory infections, including treatment of infections due to Neisseria gonorrhoeae and Chlamydia trachomatis and bioterrorism agents including Bacillus anthracis, Yersinia pestis and Francisella tularensis.

Chlamydia trachomatis ocular and urogenital infections represent major public health problems, whereas Chlamydophila pneumoniae is a common aetiological agent of community-acquired pneumonia. The obligate intracellular lifestyle of these established pathogens poses challenges to both their diagnosis and treatment. Tetracyclines, macrolides and quinolones remain the antimicrobials of choice for the treatment of infections due to Chlamydiaceae.

Three clinical Chlamydia pneumoniae isolates for which the MIC of azithromycin increased after treatment were investigated for genetic evidence of macrolide resistance. Attempts to induce antibiotic resistance in vitro were made. No genetic mechanism was identified for the phenotypic change in these C. pneumoniae isolates. No macrolide resistance was obtained in vitro.

The in vitro activities of iclaprim, a novel dihydrofolate reductase inhibitor, azithromycin, and levofloxacin were tested against 10 strains of Chlamydia trachomatis and 10 isolates of Chlamydia pneumoniae. For C. trachomatis and C. pneumoniae, the iclaprim MIC and minimal bactericidal concentration at which 90% of isolates were inhibited (MIC(90) and MBC(90)) were 0.5 micro g/ml, compared to an azithromycin MIC(90) and MBC(90) of 0.125 micro g/ml and levofloxacin MIC(90)s and MBC(90)s of 1 micro g/ml for C. trachomatis and 0.5 micro g/ml for C. pneumoniae.

The in vitro activity of NVP-PDF386 (VRC4887), a novel new peptide deformylase inhibitor, and those of levofloxacin and clarithromycin were tested against 21 isolates of Chlamydia pneumoniae. The MIC at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by NVP-PDF386 for all isolates of C. pneumoniae were 0.008 micro g/ml (range, 0.008 to 0.015 micro g/ml) compared to 0.25 and 0.06 micro g/ml for levofloxacin and clarithromycin, respectively.

Persistent infections with Chlamydia pneumoniae have been implicated in the development of chronic diseases, such as atherosclerosis and asthma. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratory C. pneumoniae infections, little is known about the dose and duration of therapy needed to treat a putative chronic C. pneumoniae infection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability of C. pneumoniae and cytokine production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminate C. pneumoniae in continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1beta, IL-4, IL-10, tumor necrosis factor alpha, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronic C. pneumoniae infection.

A number of studies have found that inflammation of the vessel wall plays an essential role in both the initiation and progression of atherosclerosis and erosion and fissure and the eventual rupture of plaques. Chlamydia pneumoniae is one of the infectious agents that have been investigated as possible causes of this inflammation. Initial studies of the association of C. pneumoniae and cardiovascular disease (CVD) were seroepidemiologic, and these were followed by studies in which the organism was identified in vascular tissue from patients with CVD by electron microscopy, PCR and immunocytochemical staining (ICC). C. pneumoniae has also been isolated by culture from vascular tissue in a small number patients. However, no single serologic, PCR, or ICC assay has been used consistently across all studies. The assays used are also not standardized. Recent studies of serologic and PCR assays for diagnosis of C. pneumoniae infection have suggested that there may be substantial interlaboratory variation in the performance of these tests. It now appears that some of the inconsistency of results from study to study may be due, in part, to lack of standardized methods. Although initial seroepidemiologic studies demonstrated a significantly increased risk of adverse cardiac outcome in patients who were seropositive, subsequent prospective studies found either small or no increased risk. In addition to the lack of consistent serologic criteria, recent evaluations have demonstrated inherent problems with performance of the most widely used serologic methods. Most importantly, we do not have a reliable serologic marker for chronic or persistent C. pneumoniae infection.

Atypical respiratory pathogens such as Mycoplasma pneumoniae and intracellular pathogens such as Legionella spp. and Chlamydia spp. form a significant proportion of the aetiological agents underlying community-acquired pneumonia (CAP). The clinical signs or radiological features of atypical pneumonia are generally insufficient to predict accurately the pathogen involved; in addition, high costs and a considerable length of time are involved in the identification of atypical pathogens. Treatment is, therefore, most often empirical, and it is important that the activity of antibacterial agents available to treat CAP is sufficiently broad to eradicate infection with both common and atypical bacterial pathogens. Telithromycin (HMR 3647) is the first of a new family of antibacterials, the ketolides, and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs). The excellent activity of telithromycin against the respiratory tract bacterial pathogens most commonly associated with community-acquired RTIs, including resistant strains, is well established. This review examines the considerable body of evidence showing that telithromycin also has a high level of activity against atypical and intracellular respiratory tract bacterial pathogens.

We evaluated the in vitro activity of GAR-936, a novel glycylcycline antibiotic, against ten isolates of Chlamydia pneumoniae and five strains of C. trachomatis. Susceptibility testing was done in HEp-2 cells. The MIC90s and MBC90s of GAR-936, doxycycline, ofloxacin and clarithromycin against C. pneumoniae were 0.125, 0.25, 0.25 and 0.06 mg/l, respectively. The MICs and MBCs of GAR-936, doxycycline, ofloxacin and clarithromycin against C. trachomatis were 0.03-0.125, 0.25, 0.25-0.5 and 0.06 mg/l, respectively. GAR-936 had excellent activity against both chlamydial species and may have a potential role in the treatment of human chlamydial infection.

Chlamydia pneumoniae is a well-established cause of community-acquired pneumonia and bronchitis in adults and children. Chronic infections with C. pneumoniae have been implicated in the development of atherosclerosis and other diseases in humans. Methods currently used for the culture and propagation of C. pneumoniae are not analogous to the infection as it occurs in vivo. We have established a model of continuous C. pneumoniae infection in vitro. HEp-2 cells inoculated with CM-1 and TW-183 strains have been persistently infected for periods of over 1.5 and 2 years, respectively. The cultures were maintained without centrifugation or the addition of cycloheximide, fresh host cells, or chlamydia. We observed cycles of host cell lysis, detachment, and regrowth with both strains of C. pneumoniae. Continuous C. pneumoniae infections may more closely resemble the actual events as they occur in vivo and, therefore, may be a better model for the in vitro study of C. pneumoniae infection. When we used continuously infected cells to determine the effects of azithromycin and ofloxacin on C. pneumoniae propagation in vitro, we found that both drugs reduced but did not completely eliminate the organism. This may be an important observation, as the failure of antibiotic therapy against C. pneumoniae infection in humans has been described.

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.

The in vitro activities of HMR 3647, roxithromycin, erythromycin, and azithromycin against 19 strains of Chlamydia pneumoniae were tested. The MIC at which 90% of the isolates are inhibited and the minimum bactericidal concentration at which 90% of the isolates are killed of HMR 3647 were 0.25 microgram/ml (range, 0.015 to 2 micrograms/ml). Nine recently obtained clinical isolates from children with pneumonia were more susceptible (MICs, 0.015 to 0.0625 microgram/ml) than older strains that had been passaged more extensively.

Chlamydia pneumoniae was eradicated from the nasopharynges of 26 of 33 (78.8%) evaluable children and adults with community-acquired pneumonia who were treated with azithromycin. We tested 55 isolates of C. pneumoniae obtained from 46 of these patients against azithromycin. The MIC at which 90% of the isolates were inhibited and the minimal chlamydiacidal concentration at which 90% of strains tested were killed of azithromycin for these isolates were both 0.5 microg/ml. Seven patients remained culture positive after treatment. The MICs of azithromycin for isolates from two patients increased fourfold after therapy. However, all the patients with persistent infection improved clinically. Further studies of treatment of C. pneumoniae infection, utilizing culture, are needed both to assess efficacy and to monitor for the possible development of antibiotic resistance.

The in-vitro susceptibilities of 12 strains of Chlamydia pneumoniae were determined for dirithromycin, a new macrolide antibiotic, erythromycyclamine, its active metabolite, and erythromycin. Both dirithromycin and erythromycyclamine had an MIC90 of 2 mg/L, as compared with 0.062 mg/L for erythromycin. The combination of dirithromycin and erythromycyclamine appeared to be additive. Determination of the role of dirithromycin for the treatment of C. pneumoniae infection will depend on the results of prospective, controlled studies utilizing culture.

The in vitro susceptibilities of 11 strains of Chlamydia pneumoniae to azithromycin, clarithromycin, erythromycin, L-oflaxacin, and doxycycline were determined. Clarithromycin was the most active agent tested, with an MIC for 90% of strains and minimal chlamydiacidal concentration for 90% of strains of 0.03 microns/ml. The activity of azithromycin was similar to those of erythromycin and doxycycline, with MICs for 90% of strains of 0.125 to 0.25 microns/ml. However, the prolonged half-life and enhanced tissue penetration of azithromycin should allow for less frequent dosing and shorter duration of therapy than with erythromycin or clarithromycin. L-Ofloxacin had activity similar to that of ofloxacin, with MICs of 0.125 to 0.5 micron/ml. From the results of this in vitro study, azithromycin and clarithromycin appear to be effective antibiotics that may have a role in the treatment of infections due to C. pneumoniae.

The in vitro susceptibilities of two clinical isolates of Chlamydia pneumoniae from Brooklyn, N.Y., were determined for tetracycline, erythromycin, sulfamethoxazole, ciprofloxacin, and three new macrolides--azithromycin, clarithromycin, and roxithromycin. Clarithromycin was the most active drug tested, followed by the other macrolides, tetracycline, and ciprofloxacin.

The activities of seven broad spectrum cephalosporins, four other beta-lactam antibiotics, and one monobactam against Chlamydia trachomatis were measured in a cell culture system. The minimal inhibitory concentration of four of the seven cephalosporins was greater than or equal to 128 micrograms/ml; those of the other three were from 16 to 32 micrograms/ml. Of the other agents, only mecillinam had activity against C. trachomatis comparable to that reported for ampicillin (minimal inhibitory concentration, less than or equal to 0.5 micrograms/ml).