for convenience , before further description of the present invention , certain terms employed in the specification , examples and appended claims are collected here . these definitions should be read in light of the remainder of the disclosure and understood as by a person of skill in the art . unless defined otherwise , all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art . the articles “ a ” and “ an ” are used herein to refer to one or to more than one ( i . e . to at least one ) of the grammatical object of the article . by way of example , “ an element ” means one element or more than one element . the term “ antibacterial ” is art - recognized and refers to the ability of the compounds of the present invention to prevent , inhibit or destroy the growth of microbes of bacteria . the terms “ antiinfective ” and “ antiinfective agent ” are used interchangeably throughout the specification to describe a biologically active agent which can kill or inhibit the growth of certain other harmful pathogenic organisms , including but not limited to bacteria , yeasts and fungi , viruses , protozoa or parasites , and which can be administered to living organisms , especially animals such as mammals , particularly humans . the term “ antimicrobial ” is art - recognized and refers to the ability of the compounds of the present invention to prevent , inhibit or destroy the growth of microbes such as bacteria , fungi , protozoa and viruses . the term “ bioavailable ” is art - recognized and refers to a form of the subject invention that allows for it , or a portion of the amount administered , to be absorbed by , incorporated to , or otherwise physiologically available to a subject or patient to whom it is administered . the terms “ comprise ” and “ comprising ” are used in the inclusive , open sense , meaning that additional elements may be included . the term “ illness ” as used herein refers to any illness caused by or related to infection by an organism . the term “ including ” is used herein to mean “ including but not limited to ”. “ including ” and “ including but not limited to ” are used interchangeably . the term “ lipid - based composition ” as used herein refers to compositions that primarily comprise lipids . non - limiting examples of lipid - based compositions may take the form of coated lipid particles , liposomes , emulsions , micelles , and the like . the term “ mammal ” is known in the art , and exemplary mammals include humans , primates , bovines , porcines , canines , felines , and rodents ( e . g ., mice and rats ). the term “ microbe ” is art - recognized and refers to a microscopic organism . in certain embodiments the term microbe is applied to bacteria . in other embodiments the term refers to pathogenic forms of a microscopic organism . a “ patient ,” “ subject ” or “ host ” to be treated by the subject method may mean either a human or non - human animal . the term “ pharmaceutically - acceptable salts ” is art - recognized and refers to the relatively non - toxic , inorganic and organic acid addition salts of compounds , including , for example , those contained in compositions of the present invention . the term “ prodrug ” is art - recognized and is intended to encompass compounds which , under physiological conditions , are converted into the antibacterial agents of the present invention . a common method for making a prodrug is to select moieties which are hydrolyzed under physiological conditions to provide the desired compound . in other embodiments , the prodrug is converted by an enzymatic activity of the host animal or the target bacteria . the term “ treating ” is art - recognized and refers to curing as well as ameliorating at least one symptom of any condition or disease . the lipids used in the pharmaceutical formulations of the present invention can be synthetic , semi - synthetic or naturally - occurring lipids , including phospholipids , tocopherols , sterols , fatty acids , glycoproteins such as albumin , negatively - charged lipids and cationic lipids . in terms of phosholipids , they could include such lipids as egg phosphatidylcholine ( epc ), egg phosphatidylglycerol ( epg ), egg phosphatidylinositol ( epi ), egg phosphatidylserine ( eps ), phosphatidylethanolamine ( epe ), and phosphatidic acid ( epa ); the soya counterparts , soy phosphatidylcholine ( spc ); spg , sps , spi , spe , and spa ; the hydrogenated egg and soya counterparts ( e . g ., hepc , hspc ), other phospholipids made up of ester linkages of fatty acids in the 2 and 3 of glycerol positions containing chains of 12 to 26 carbon atoms and different head groups in the i position of glycerol that include choline , glycerol , inositol , serine , ethanolamine , as well as the corresponding phosphatidic acids . the chains on these fatty acids can be saturated or unsaturated , and the phospholipid may be made up of fatty acids of different chain lengths and different degrees of unsaturation . in particular , the compositions of the formulations can include dipalmitoylphosphatidylcholine ( dppc ), a major constituent of naturally - occurring lung surfactant . other examples include dimyristoylphosphatidycholine ( dmpc ) and dimyristoylphosphatidylglycerol ( dmpg ) dipalmitoylphosphatidcholine ( dppq and dipalmitoylphosphatidylglycerol ( dppg ) distearoylphosphatidylcholine ( dspq and distearoylphosphatidylglycerol ( dspg ), dioleylphosphatidyl - ethanolamine ( dope ) and mixed phospholipids like palmitoylstearoylphosphatidyl - choline ( pspc ) and palmiloylstearolphosphatidylglycerol ( pspg ), and single acylated phospholipids like mono - oleoyl - phosphatidylethanolamine ( mope ). the sterols can include , cholesterol , esters of cholesterol including cholesterol hemi - succinate , salts of cholesterol including cholesterol hydrogen sulfate and cholesterol sulfate , ergosterol , esters of ergosterol including ergosterol hemi - succinate , salts of ergosterol including ergosterol hydrogen sulfate and ergosterol sulfate , lanosterol , esters of lanosterol including lanosterol hemi - succinate , salts of lanosterol including lanosterol hydrogen sulfate and lanosterol sulfate . the tocopherols can include tocopherols , esters of tocopherols including tocopherol hemi - succinates , salts of tocopherols including tocopherol hydrogen sulfates and tocopherol sulfates . the term “ sterol compound ” includes sterols , tocopherols and the like . the cationic lipids used can include ammonium salts of fatty acids , phospholids and glycerides . the fatty acids include fatty acids of carbon chain lengths of 12 to 26 carbon atoms that are either saturated or unsaturated . some specific examples include : myristylamine , palmitylamine , laurylamine and stearylamine , dilauroyl ethylphosphocholine ( dlep ), dimyristoyl ethylphosphocholine ( dmep ), dipalmitoyl ethylphosphocholine ( dpep ) and distearoyl ethylphosphocholine ( dsep ), n -( 2 , 3 - di -( 9 -( z )- octadecenyloxy )- prop - 1 - yl - n , n , n - trimethylammonium chloride ( dotma ) and 1 , 2 - bis ( oleoyloxy )- 3 -( trimethylammonio ) propane ( dotap ). the negatively - charged lipids which can be used include phosphatidyl - glycerols ( pgs ), phosphatidic acids ( pas ), phosphatidylinositols ( pis ) and the phosphatidyl serines ( pss ). examples include dmpg , dppg , dspg , dmpa , dppa , dspa , dmpi , dppi , dspi , dmps , dpps and dsps . phosphatidylcholines , such as dppc , aid in the uptake by the cells in the lung ( e . g ., the alveolar macrophages ) and helps to sustain release of the bioactive agent in the lung . the negatively charged lipids such as the pgs , pas , pss and pis , in addition to reducing particle aggregation , are believed to play a role in the sustained release characteristics of the inhalation formulation as well as in the transport of the formulation across the lung ( transcytosis ) for systemic uptake . the sterol compounds are believed to affect the release characteristics of the formulation . liposomes are completely closed lipid bilayer membranes containing an entrapped aqueous volume . liposomes may be unilamellar vesicles ( possessing a single membrane bilayer ) or multilamellar vesicles ( onion - like structures characterized by multiple membrane bilayers , each separated from the next by an aqueous layer ). the bilayer is composed of two lipid monolayers having a hydrophobic “ tail ” region and a hydrophilic “ head ” region . the structure of the membrane bilayer is such that the hydrophobic ( nonpolar ) “ tails ” of the lipid monolayers orient toward the center of the bilayer while the hydrophilic “ heads ” orient towards the aqueous phase . liposomes can be produced by a variety of methods ( for a review , see , e . g ., cullis et al . ( 1987 )). bangham &# 39 ; s procedure ( j . mol . biol . ( 1965 )) produces ordinary multilamellar vesicles ( mlvs ). lenk et al . ( u . s . pat . nos . 4 , 522 , 803 , 5 , 030 , 453 and 5 , 169 , 637 ). fountain et al . ( u . s . pat . no . 4 , 588 , 578 ) and cullis et al . ( u . s . pat . no . 4 , 975 , 282 ) disclose methods for producing multilamellar liposomes having substantially equal interlamellar solute distribution in each of their aqueous compartments . paphadjopoulos et al ., u . s . pat . no . 4 , 235 , 871 , discloses preparation of oligolamellar liposomes by reverse phase evaporation . unilamellar vesicles can be produced from mlvs by a number of techniques , for example , the extrusion of cullis et al . ( u . s . pat . no . 5 , 008 , 050 ) and loughrey et al . ( u . s . pat . no . 5 , 059 , 421 )). sonication and homogenization cab be so used to produce smaller unilamellar liposomes from larger liposomes ( see , for example , paphadjopoulos et al . ( 1968 ); deamer and uster ( 1983 ); and chapman et al . ( 1968 )). the original liposome preparation of bangham et al . ( j . mol . biol ., 1965 , 13 : 238 - 252 ) involves suspending phospholipids in an organic solvent which is then evaporated to dryness leaving a phospholipid film on the reaction vessel . next , an appropriate amount of aqueous phase is added , the 60 mixture is allowed to “ swell ”, and the resulting liposomes which consist of multilamellar vesicles ( mlvs ) are dispersed by mechanical means . this preparation provides the basis for the development of the small sonicated unilamellar vesicles described by papahadjopoulos et al . ( biochim . biophys , acta ., 1967 , 135 : 624 - 638 ), and large unilamellar vesicles . techniques for producing large unilamellar vesicles ( luvs ), such as , reverse phase evaporation , infusion procedures , and detergent dilution , can be used to produce liposomes . a review of these and other methods for producing liposomes may be found in the text liposomes . marc ostro , ed ., marcel dekker , inc ., new york , 1983 , chapter 1 , the pertinent portions of which are incorporated herein by reference . see also szoka , jr . et al ., ( 1980 , ann . rev . biophys . bioeng ., 9 : 467 ), the pertinent portions of which are also incorporated herein by reference . other techniques that are used to prepare vesicles include those that form reverse - phase evaporation vesicles ( rev ), papahadjopoulos et al ., u . s . pat . no . 4 , 235 , 871 . another class of liposomes that may be used are those characterized as having substantially equal lamellar solute distribution . this class of liposomes is denominated as stable plurilamellar vesicles ( splv ) as defined in u . s . pat . no . 4 , 522 , 803 to lenk , et al . and includes monophasic vesicles as described in u . s . pat . no . 4 , 588 , 578 to fountain , et al . and frozen and thawed multilamellar vesicles ( fatmlv ) as described above . a variety of sterols and their water soluble derivatives such as cholesterol hemisuccinate have been used to form liposomes ; see specifically janoff et al ., u . s . pat . no . 4 , 721 , 612 , issued jan . 26 , 1988 , entitled “ steroidal liposomes .” mayhew et al ., pct publication no . wo 85 / 00968 , published mar . 14 , 1985 , described a method for reducing the toxicity of drugs by encapsulating them in liposomes comprising alpha - tocopherol and certain derivatives thereof . also , a variety of tocopherols and their water soluble derivatives have been used to form liposomes , see janoff et al ., pct publication no . 87 / 02219 , published apr . 23 , 1987 , entitled “ alpha tocopherol - based vesicles ”. the liposomes are comprised of particles with a mean diameter of approximately 0 . 01 microns to approximately 3 . 0 microns , preferably in the range about 0 . 2 to 1 . 0 microns . the sustained release property of the liposomal product can be regulated by the nature of the lipid membrane and by inclusion of other excipients ( e . g ., sterols ) in the composition . the infective agent included in the scope of the present invention may be a bacteria . the bacteria can be selected from : pseudomonas aeruginosa , bacillus anthracis , listeria monocytogenes , staphylococcus aureus , salmonellosis , yersina pestis , mycobacterium leprae , m . africanum , m . asiaticum , m . avium - intracellulaire , m . chelonei abscessus , m . fallax , m . fortuitum , m . kansasii , m . leprae , m . mainoense , m . shimoidei , m . simiae , m . szulgai , m . xenopi , m . tuberculosis , brucella melitensis , brucella suis , brucella abortus , brucella canis , legionella pneumonophilia , francisella tularensis , pneumocystis carinii , mycoplasma , and burkholderia cepacia . the infective agent included in the scope of the present invention can be a virus . the virus can be selected from : hantavirus , respiratory syncytial virus , influenza , and viral pneumonia . the infective agent included in the scope of the present invention can be a fungus . fungal diseases of note include : aspergillosis , disseminated candidiasis , blastomycosis , coccidioidomycosis , cryptococcosis , histoplasmosis , mucormycosis , and sporotrichosis . the term antiinfective agent is used throughout the specification to describe a biologically active agent which can kill or inhibit the growth of certain other harmful pathogenic organisms , including but not limited to bacteria , yeasts and fungi , viruses , protozoa or parasites , and which can be administered to living organisms , especially animals such as mammals , particularly humans . non - limiting examples of antibiotic agents that may be used in the antiinfective compositions of the present invention include cephalosporins , quinolones and fluoroquinolones , penicillins , and beta lactamase inhibitors , carbepenems , monobactams , macrolides and lincosamines , glycopeptides , rifampin , oxazolidonones , tetracyclines , aminoglycosides , streptogramins , sulfonamides , and others . each family comprises many members . cephalosporins are further categorized by generation . non - limiting examples of cephalosporins by generation include the following . examples of cephalosporins i generation include celadroxil , cefazolin , cephalexin , cephalothin , cephapirin , and cephradine . examples of cephalosporins ii generation include cefaclor , cefamandol , cefonicid , cefotetan , cefoxitin , cefprozil , ceftmetazole , cefuroxime , cefuroxime axetil , and loracarbef . examples of cephalosporins iii generation include cefdinir , ceftibuten , cefditoren , cefetamet , cefpodoxime , celprozil , cefuroxime ( axetil ), cefuroxime ( sodium ), cefoperazone , cefixime , cefotaxime , cefpodoxime proxetil , ceftazidime , ceftizoxime , and ceftriaxone . examples of cephalosporins iv generation include cefepime . non - limiting examples of quinolones and fluoroquinolones include cinoxacin , ciprofloxacin , enoxacin , gatifloxacin , grepafloxacin , levofloxacin , lomefloxacin , moxifioxacin , nalidixic acid , norfloxacin , ofloxacin , sparfloxacin , trovafloxacin , oxolinic acid , gemifloxacin , and perfloxacin . non - limiting examples of penicillins include amoxicillin , ampicillin , bacampicillin , carbenicillin indanyl , mezlocillin , piperacillin , and ticarcillin . non - limiting examples of penicillins and beta lactamase inhibitors include amoxicillin - clavulanic acid , ampicillin - sulbactam , sulfactam , tazobactam , benzylpenicillin , cloxacillin , dicloxacillin , methicillin , oxacillin , penicillin g ( benzathine , potassium , procaine ), penicillin v , penicillinase - resistant penicillins , isoxazoylpenicillins , aminopenicillins , ureidopenicillins , piperacillin + tazobactam , ticarcillin + clavulanic acid , and nafcillin . non - limiting examples of macrolides and lincosamines include azithromycin , clarithromycin , clindamycin , dirithromycin , erythromycin , lincomycin , and troleandomycin . non - limiting examples of tetracyclines include demeclocycline , doxycycline , methacycline , minocycline , oxytetracycline , tetracycline , and chlortetracycline . non - limiting examples of aminoglycosides include amikacin , gentamicin , kanamycin , neomycin , netilmicin , streptomycin , tobramycin , and paromomycin . non - limiting examples of sulfonamides include mafenide , silver sulfadiazine , sulfacetamide , sulfadiazine , sulfamethoxazole , sulfasalazine , sulfisoxazole , trimethoprim - sulfmethoxazole , and sulfamethizole . non - limiting examples of other antibiotic agents include bacitracin , chloramphenicol , colistemetate , fosfomycin , isoniazid , methenamine , metronidazol , mupirocin , nitrofurantoin , nitrofurazone , novobiocin , polymyxin b , spectinomycin , trimethoprine , trimethoprine / sulfamethoxazole , cationic peptides , colistin , iseganan , cycloserine , capreomycin , pyrazinamide , para - aminosalicyclic acid , and erthromycin ethylsuccinate + sulfisoxazole . antiviral agents include , but are not limited to : zidovudine , acyclovir , ganciclovir , vidarabine , idoxuridine , trifluridine , ribavirin , interferon alpha - 2a , interferon alpha - 2b , interferon beta , interferon gamma ). antifungal agents include , but are not limited to : amphotericin b , nystatin , hamycin , natamycin , pimaricin , ambruticin , itraconazole , terconazole , ketoconazole , voriconazole , miconazole , nikkomycion z , griseofulvin , candicidin , cilofungin , chlotrimazole , clioquinol , caspufungin , tolnaflate . the dosage of any compositions of the present invention will vary depending on the symptoms , age and body weight of the patient , the nature and severity of the disorder to be treated or prevented , the route of administration , and the form of the subject composition . any of the subject formulations may be administered in a single dose or in divided doses . dosages for the compositions of the present invention may be readily determined by techniques known to those of skill in the art or as taught herein . in certain embodiments , the dosage of the subject compounds will generally be in the range of about 0 . 01 ng to about 10 g per kg body weight , specifically in the range of about 1 ng to about 0 . 1 g per kg , and more specifically in the range of about 100 ng to about 10 mg per kg . an effective dose or amount , and any possible affects on the timing of administration of the formulation , may need to be identified for any particular composition of the present invention . this may be accomplished by routine experiment as described herein , using one or more groups of animals ( preferably at least 5 animals per group ), or in human trials if appropriate . the effectiveness of any subject composition and method of treatment or prevention may be assessed by administering the composition and assessing the effect of the administration by measuring one or more applicable indices , and comparing the post - treatment values of these indices to the values of the same indices prior to treatment . the precise time of administration and amount of any particular subject composition that will yield the most effective treatment in a given patient will depend upon the activity , pharmacokinetics , and bioavailability of a subject composition , physiological condition of the patient ( including age , sex , disease type and stage , general physical condition , responsiveness to a given dosage and type of medication ), route of administration , and the like . the guidelines presented herein may be used to optimize the treatment , e . g ., determining the optimum time and / or amount of administration , which will require no more than routine experimentation consisting of monitoring the subject and adjusting the dosage and / or timing . while the subject is being treated , the health of the patient may be monitored by measuring one or more of the relevant indices at predetermined times during the treatment period . treatment , including composition , amounts , times of administration and formulation , may be optimized according to the results of such monitoring . the patient may be periodically reevaluated to determine the extent of improvement by measuring the same parameters . adjustments to the amount ( s ) of subject composition administered and possibly to the time of administration may be made based on these reevaluations . treatment may be initiated with smaller dosages which are less than the optimum dose of the compound . thereafter , the dosage may be increased by small increments until the optimum therapeutic effect is attained . the use of the subject compositions may reduce the required dosage for any individual agent contained in the compositions ( e . g ., the fab1 inhibitor ) because the onset and duration of effect of the different agents may be complimentary . toxicity and therapeutic efficacy of subject compositions may be determined by standard pharmaceutical procedures in cell cultures or experimental animals , e . g ., for determining the ld 50 and the ed 50 . the data obtained from the cell culture assays and animal studies may be used in formulating a range of dosage for use in humans . the dosage of any subject composition lies preferably within a range of circulating concentrations that include the ed 50 with little or no toxicity . the dosage may vary within this range depending upon the dosage form employed and the route of administration utilized . for compositions of the present invention , the therapeutically effective dose may be estimated initially from cell culture assays . the pharmaceutical formulation of the antiinfective may be comprised of either an aqueous dispersion of liposomes and free antiinfective , or a dehydrated powder containing liposomes and free antiinfective . the formulation may contain lipid excipients to form the liposomes , and salts / buffers to provide the appropriate osmolarity and ph . the dry powder formulations may contain additional excipients to prevent the leakage of encapsulated antiinfective during the drying and potential milling steps needed to create a suitable particle size for inhalation ( i . e ., 1 - 5 μm ). such excipients are designed to increase the glass transition temperature of the antiinfective formulation . the pharmaceutical excipient may be a liquid or solid filler , diluent , solvent or encapsulating material , involved in carrying or transporting any subject composition or component thereof from one organ , or portion of the body , to another organ , or portion of the body . each excipient must be “ acceptable ” in the sense of being compatible with the subject composition and its components and not injurious to the patient . suitable excipients include trehalose , raffinose , mannitol , sucrose , leucine , trileucine , and calcium chloride . examples of other suitable excipients include ( 1 ) sugars , such as lactose , and glucose ; ( 2 ) starches , such as corn starch and potato starch ; ( 3 ) cellulose , and its derivatives , such as sodium carboxymethyl cellulose , ethyl cellulose and cellulose acetate ; ( 4 ) powdered tragacanth ; ( 5 ) malt ; ( 6 ) gelatin ; ( 7 ) talc ; ( 8 ) excipients , such as cocoa butter and suppository waxes ; ( 9 ) oils , such as peanut oil , cottonseed oil , safflower oil , sesame oil , olive oil , corn oil and soybean oil ; ( 10 ) glycols , such as propylene glycol ; ( 11 ) polyols , such as glycerin , sorbitol , and polyethylene glycol , ( 12 ) esters , such as ethyl oleate and ethyl laurate ; ( 13 ) agar ; ( 14 ) buffering agents , such as magnesium hydroxide and aluminum hydroxide ; ( 15 ) alginic acid ; ( 16 ) pyrogen - free water ; ( 17 ) isotonic saline ; ( 18 ) ringer &# 39 ; s solution ; ( 19 ) ethyl alcohol ; ( 20 ) phosphate buffer solutions ; and ( 21 ) other non - toxic compatible substances employed in pharmaceutical formulations . the pharmaceutical formulations of the present invention may be used in any dosage dispensing device adapted for intranasal administration . the device should be constructed with a view to ascertaining optimum metering accuracy and compatibility of its constructive elements , such as container , valve and actuator with the nasal formulation and could be based on a mechanical pump system , e . g ., that of a metered - dose nebulizer , dry powder inhaler , soft mist inhaler , or a nebulizer . due to the large administered dose , preferred devices include jet nebulizers ( e . g ., pari lc star , akita ), soft mist inhalers ( e . g ., pari e - flow ), and capsule - based dry powder inhalers ( e . g ., ph & amp ; t turbospin ). suitable propellants may be selected among such gases as fluorocarbons , hydrocarbons , nitrogen and dinitrogen oxide or mixtures thereof . the inhalation delivery device can be a nebulizer or a metered dose inhaler ( mdi ), or any other suitable inhalation delivery device known to one of ordinary skill in the art . the device can contain and be used to deliver a single dose of the antiinfective compositions or the device can contain and be used to deliver multi - doses of the compositions of the present invention . a nebulizer type inhalation delivery device can contain the compositions of the present invention as a solution , usually aqueous , or a suspension . in generating the nebulized spray of the compositions for inhalation , the nebulizer type delivery device may be driven ultrasonically , by compressed air , by other gases , electronically or mechanically . the ultrasonic nebulizer device usually works by imposing a rapidly oscillating waveform onto the liquid film of the formulation via an electrochemical vibrating surface . at a given amplitude the waveform becomes unstable , whereby it disintegrates the liquids film , and it produces small droplets of the formulation . the nebulizer device driven by air or other gases operates on the basis that a high pressure gas stream produces a local pressure drop that draws the liquid formulation into the stream of gases via capillary action . this fine liquid stream is then disintegrated by shear forces . the nebulizer may be portable and hand held in design , and may be equipped with a self contained electrical unit . the nebulizer device may comprise a nozzle that has two coincident outlet channels of defined aperture size through which the liquid formulation can be accelerated . this results in impaction of the two streams and atomization of the formulation . the nebulizer may use a mechanical actuator to force the liquid formulation through a multiorifice nozzle of defined aperture size ( s ) to produce an aerosol of the formulation for inhalation . in the design of single dose nebulizers , blister packs containing single doses of the formulation may be employed . in the present invention the nebulizer may be employed to ensure the sizing of particles is optimal for positioning of the particle within , for example , the pulmonary membrane . a metered dose inhalator ( mdi ) may be employed as the inhalation delivery device for the compositions of the present invention . this device is pressurized ( pmdi ) and its basic structure comprises a metering valve , an actuator and a container . a propellant is used to discharge the formulation from the device . the composition may consist of particles of a defined size suspended in the pressurized propellant ( s ) liquid , or the composition can be in a solution or suspension of pressurized liquid propellant ( s ). the propellants used are primarily atmospheric friendly hydroflourocarbons ( hfcs ) such as 134a and 227 . traditional chloroflourocarbons like cfc - 11 , 12 and 114 are used only when essential . the device of the inhalation system may deliver a single dose via , e . g ., a blister pack , or it may be multi dose in design . the pressurized metered dose inhalator of the inhalation system can be breath actuated to deliver an accurate dose of the lipid - containing formulation . to insure accuracy of dosing , the delivery of the formulation may be programmed via a microprocessor to occur at a certain point in the inhalation cycle . the mdi may be portable and hand held . pharmacokinetics of amikacin delivered as both free and encapsulated amikacin in healthy volunteers . the nebulized liposomal amikacin contains a mixture of encapsulated ( ca ., 60 %) and free amikacin ( ca ., 40 %). following inhalation in healthy volunteers the corrected nominal dose was 100 mg as determined by gamma scintigraphy . fig1 depicts the lung concentration of amikacin and tobi ® ( administered 100 % free ), based on pharmacokinetic modeling of serum concentrations over time . both curves assume a volume of distribution for aminoglycosides in the lung of 200 ml . interestingly , the peak levels of antiinfective in the lung are approximately equivalent for the 100 mg dose of liposomal amikacin , and the 300 mg dose of tobi ®. this is a consequence of the rapid clearance of the free tobramycin from the lung by absorption into the systemic circulation with a half - life of about 1 . 5 hr . these results serve as a demonstration of the improved lung targeting afforded by liposomal encapsulation . the presence of free and encapsulated antiinfective in the amikacin formulation is demonstrated by the two component pharmacokinetic profile observed . free amikacin is rapidly absorbed into the systemic circulation ( with a half - life similar to tobi ), while the encapsulated drug has a lung half - life of approximately 45 hr . the free amikacin is available to provide bactericidal activity , while the encapsulated drug provides sustained levels of drug in the lung , enabling improved killing of resistant bacterial strains . the measured lung concentrations for the liposomal compartment are significantly above the mic 50 of 1240 clinical isolates of pseudomonas aeruginosa , potentially reducing the development of resistance . impact of free amikacin on the percentage of amikacin encapsulated in liposomes following nebulization . liposomal preparations of amikacin may exhibit significant leakage of encapsulated drug during nebulization . as detailed in table 1 below , the presence of free amikacin in solution was shown to surprisingly decrease the leakage of antiinfective by about four - fold from the liposome . while not wishing to be limited to any particular theory , it is hypothesized that liposomes break - up and re - form during nebulization , losing encapsulated antiinfective in the process . alternatively , encapsulated antiinfective is lost during nebulization because the liposome membrane becomes leaky . when an excess of free antiinfective is present in solution , the free antiinfective is readily available in close proximity to the liposome , and is available to be taken back up into the liposome on re - formation . those skilled in the art will recognize , or be able to ascertain using no more than routine experimentation , many equivalents to the specific embodiments of the invention described herein . such equivalents are intended to be encompassed by the following claims .
a system for treating or providing prophylaxus against a pulmonary infection is disclosed comprising : a ) a pharmaceutical formulation comprising a mixture of free antiinfective and antiinfective encapsulated in a lipid - based composition , and b ) an inhalation delivery device . a method for providing prophylaxis against a pulmonary infection in a patient and a method of reducing the loss of antiinfective encapsulated in a lipid - based composition upon nebulization comprising administering an aerosolized pharmaceutical formulation comprising a mixture of free antiinfective and antiinfective encapsulated in a lipid - based composition is also disclosed .