zithromax and Neutropenia

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Interactions; Female; Humans; Male; Neutropenia; Rifabutin

A 60-year-old female patient living in Southeast China presented with persistent fever, chills, night sweats, fatigue, and dizziness of 12-day duration. Blood tests showed neutropenia, thrombocytopenia, and active hemolytic anemia, with elevated C-reactive protein. Broad-spectrum antibiotics were administered for a possible diagnosis of sepsis, without any response. Malaria was initially diagnosed after visualizing intraerythrocytic ring-shaped parasites in bone marrow and blood smears. The patient resided in an area of unstable endemicity for Plasmodium falciparum. Blood samples were sent to the Centers for Disease Control and Prevention and a definitive diagnosis of human babesiosis was made using Babesia microti-specific PCR. Chloroquine phosphate and clindamycin were started and the patient became normothermic. However, due to the intolerable adverse effects of the antibiotics, intravenous azithromycin was given as an alternative. The patient recovered from fever and hemolysis, and repeated peripheral blood smears showed hemoparasite clearance. Cases of human babesiosis are rarely reported and probably under-diagnosed in China; therefore, improving our understanding of this disease as a newly emerging public health threat is imperative.

Topics: Administration, Intravenous; Anemia, Hemolytic; Anti-Bacterial Agents; Azithromycin; Babesiosis; C-Reactive Protein; China; Chloroquine; Clindamycin; Female; Fever; Humans; Middle Aged; Neutropenia; Thrombocytopenia

Topics: Aged, 80 and over; Agranulocytosis; Anti-Bacterial Agents; Azithromycin; Granulocyte Colony-Stimulating Factor; Humans; Male; Neutropenia; Pneumonia, Mycoplasma; Pulmonary Disease, Chronic Obstructive; Treatment Outcome

Pseudomonas aeruginosa (PA) is one of the major opportunistic pathogens which can cause chronic lung infection of cystic fibrosis (CF). The formation of PA biofilm promotes CF development and restricts the antimicrobial efficacies of current antibiotics.. The antimicrobial effects of azithromycin (AZM) and berberine (BER) alone and in combination were evaluated using microdilution method, checkerboard assay, time-kill test, qRT-PCR analysis and absorption method. The treatments of AZM and/or BER were further evaluated in an animal lung infection model via observing survival rate, bacterial burden and histopathology of lung, the levels of pro-/anti-inflammatory cytokines.. AZM-BER were demonstrated to be synergistic against ten clinical PA isolates as well as the standard reference PA ATCC27853, in which PA03 was the most susceptible isolate to AZM-BER with FICI of 0.13 and chosen for subsequent experiments. The synergism of AZM-BER was further confirmed against PA03 in time-kill test and scanning electron microscope (SEM) at their concentrations showing synergism. In PA03, we found that AZM-BER could significantly attenuate productions of a series of virulence factors including alginate, LasA protease, LasB protease, pyoverdin, pyocyanin, chitinase as well as extracellular DNA, and remarkably inhibit the levels of quorum sensing (QS) molecules and the expressions of lasI, lasR, rhlI, rhlR at 1/2×MIC, 1×MIC and 2×MIC. In the infection model, the mice survival were increased markedly, the inflammations of infected lungs were improved greatly along with reduced IL-6, IL-8 and ascended IL-10 at 0.8 mg/kg of AZM combined with 3.2 mg/kg of BER.. BER might be a promising synergist to enhance the antimicrobial activity of AZM in vitro and in vivo.

Topics: Alginates; Animals; Anti-Bacterial Agents; Azithromycin; Bacterial Proteins; Berberine; Biofilms; Chitinases; Cyclophosphamide; Cystic Fibrosis; DNA, Bacterial; Drug Combinations; Drug Synergism; Glucuronic Acid; Hexuronic Acids; Humans; Lung; Metalloendopeptidases; Metalloproteases; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Neutropenia; Oligopeptides; Pseudomonas aeruginosa; Pseudomonas Infections; Pyocyanine; Virulence Factors

Non-tuberculous mycobacterial adenitis is getting more common in our environment. Epidemiologic studies and clinical trials published nowadays are limited. We present a 2-years-old boy diagnosed of Mycobacterium intracellulare adenitis and severe neutropenia as side effect of combined treatment with oral azythromycin and rifabutin, which recovers after suspending the second one. Liver metabolism of macrolide seems to increase other drugs toxicity, in this case, rifabutin. The patient eventually needed surgery due to persistence of the adenitis despite treatment with antibiotics.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Drug Therapy, Combination; Humans; Lymphadenitis; Male; Mycobacterium Infections, Nontuberculous; Neutropenia; Rifabutin; Severity of Illness Index

Utilizing a fully synthetic route to tetracycline analogues, the C-9 side-chain of the fluorocyclines was optimized for both antibacterial activity and oral efficacy. Compounds were identified that overcome both efflux (tet(K), tet(A)) and ribosomal protection (tet(M)) tetracycline-resistance mechanisms and are active against Gram-positive and Gram-negative organisms. A murine systemic infection model was used as an oral efficacy screen to rapidly identify compounds with oral bioavailability. Two compounds were identified that exhibit both oral bioavailability in rat and clinically relevant bacterial susceptibility profiles against major respiratory pathogens. One compound demonstrated oral efficacy in rodent lung infection models that was comparable to marketed antibacterial agents.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Biological Availability; Cyclophosphamide; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Lung; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Neutropenia; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections; Ribosomes; Sepsis; Stereoisomerism; Structure-Activity Relationship; Tetracycline Resistance; Tetracyclines

A 56-year-old man with a history of rheumatoid arthritis presented with a 2-day history of worsening pain in his left foot. Treatment with high-dose steroids was of no benefit, hence a diagnosis of septic arthritis was considered. However, the patient's condition deteriorated despite empirical antibiotic therapy. Following persistent investigation, the cause was identified as a fastidious Legionella longbeachae infection, and appropriate antibiotic therapy led to complete resolution of the sepsis. This emphasises the importance of considering infections with atypical organisms in patients on immunosuppressive therapy.

Topics: Arthritis, Rheumatoid; Aza Compounds; Azithromycin; Drug Therapy, Combination; Fluoroquinolones; Humans; Legionella longbeachae; Legionellosis; Male; Middle Aged; Moxifloxacin; Neutropenia; Osteomyelitis; Quinolines; Steroids

BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models.. MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays. Profiling of the pharmacokinetics and select tissue disposition in mice was determined and compared with that of the macrolide, azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were conducted using a peritonitis model, as well as lung and thigh burden models of infection.. BB-81384 selectively inhibited PDF with an IC(50) approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae pathogens. Pharmacokinetic analysis revealed good oral bioavailability and moderate clearance and volume of distribution. BB-81384 partitioning to lung tissue was similar in terms of magnitude and kinetics to that of the plasma compartment. Single-administration oral efficacy in a mouse peritonitis model was evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by approximately 5 and 3 log units in organ-burden models of lung and thigh infection, respectively.. BB-81384, a novel PDF inhibitor with good activity against S. pneumoniae in vitro, was the first compound of this class to be profiled for oral pharmacokinetics and tissue disposition and to demonstrate oral anti-pneumococcal efficacy in mice.

Topics: Amidohydrolases; Amoxicillin-Potassium Clavulanate Combination; Animals; Anti-Bacterial Agents; Azithromycin; Bacteria; Drug Therapy, Combination; Enzyme Inhibitors; Kinetics; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Muscle, Skeletal; Muscular Diseases; Neutropenia; Peritonitis; Piperazines; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Tissue Distribution

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Neutropenia; Rifabutin