One important aspect of recovery from alcohol/drug abuse is detoxification. A lot of individuals have taken that first step but have done in wrongly. In this article, we shall look at how to take your first step to redemption from alcohol and drugs addictions in the right way.

What Is Detoxification?

The term “detoxification” can mean a lot of things in medicine. For the purpose of this article, we shall look at detox from the angle of alcohol and drugs i.e. opioids, benzodiazepines, and alcohols.

A patient that requires detox from alcohol (alcohol detox) will be required to stop the intake of alcohol. In order to allow the body to cope with the abrupt stop in the supply of alcohol, medications which have moderate side effects are administered. Medications belonging to the Benzodiazepine family such as oxazepam (Serax), lorazepam (Ativan), chlordiazepoxide (Librium), and diazepam (Valium) are used for alcohol detox. There are times alcohol detox uses other classes of medications like barbiturates and anti-seizure medications.

Most of the alcohol detox usually kickstarts 24-hours after evaluation. During this period of time, the patient's vital signs such as the ability to walk, respiration, pulse and blood pressure are used to determine the type of medication that will best suit the individual. There is a gradual reduction in the dosage administered on daily basis. The treatment process lasts for 5 days after which the individual is completely detoxed from alcohol.

There is a general approach that can be adopted in order to detox from benzodiazepines. The patient’s intake is gradually reduced on a daily basis. This detoxing process takes a longer time as compared with that of alcohol. This can last for several months as an outpatient. During this detoxing, the vital signs of the individual are taken on a daily basis throughout the treatment process and the use of non-benzodiazepine medications can be employed in reducing the discomfort associated with withdrawal.

Opioid detox is carried out by replacing the illicit opioids used by the patient with methadone, buprenorphine and other safely prescribed medications containing opioids.

Potential Effects of Withdrawing from Alcohol and Drugs

There are slight discomforts that are associated with withdrawal from alcohol and drugs, some of them are listed below:

  • Dehydration
  • Diarrhea
  • Headaches
  • Insomnia
  • Leg cramps
  • Mild to severe anxiety
  • Nausea
  • A runny nose
  • Shaky hands
  • A strong craving for the drugs and alcohol.
  • Vomiting
  • Watery eyes


The severe cases of withdrawal can be very life threatening and can lead to delirium tremens and seizures.

How to identify individuals who need Detox

The need for detox depends on how long an individual has been drinking or addicted to the substance. Do not wait until the individual crash due to an overdose of the drug or alcohol. Report the case as soon as you notice it.


It is highly recommended that the patients continue with the use of some therapy even after complete detoxification. This therapy includes but is not limited to; self-help groups, individual therapy, residential treatment and outpatient treatment.


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Why are we questioning Opiate Replacement Medication and Naltrexone for Opioid Dependence?


A very important question that should be asked would be what medication replacement options are available for overcoming opioid addiction. A lot of questions have been raised about replacing opioid problems with the use of another medication. Visit at:

Most of the problems faced when struggling with opioid addiction to either heroin or pain medication are almost nonexistent when struggling with smoking problems. Several Nicotine Replacement Therapies are available to help you through quitting smoking. Some of the popular treatments deemed to be effective for quitters are; nicotine gum, nasal spray, lozenge, nicotine patch and other available medication.

These available medication are sometimes covered by your insurance company and a lot of other available means of quitting like the nicotine patch, nicotine gum or lozenges are very easy to come by and are quite cheap. Whereas getting Opiate Replacement Medication has proven to be quite difficult.

Most Opiate Replacement Medication would likely not be covered by your insurance company and are very expensive to purchase. Another problem is getting a doctor willing to prescribe these medications or getting a place to purchase them.

Several fringe benefits are even available for those willing to quit smoking. Some states provide hot-lines for quitters where you can get replacement options and some free nicotine patches.

There are several Food and Drug Administration approved treatment for opioid addiction which are backed up with evidences of their effectiveness. These treatment options ensure long term recovery and reduces the rate of overdose. Despite these available treatment that can be trusted, there are a lot of reservations by people including doctors in recommending the treatment just because it seems like you are replacing one drug addiction with another drug.

A lot of doctors have not been brought up to date about the effectiveness of Opiate Replacement Medication and this has increased the likelihood of not offering these medication as a treatment method for opioid dependence. Some medical care practitioners would likely advice against them and create a negative outlook to Opiate Replacement Medication.

Dependence on Opioids has led to overdose which has become a leading cause of death of people younger than fifty years and continues to rise each year. The increase of opioid addiction in the country is quite alarming and addiction is not only limited to the young but can extend to seniors who are most likely getting opioid prescriptions to treat pain related conditions.

Finally, with quite a large number of Nicotine Replacement Therapies available to help combat smoking addiction, creating a general awareness and training for the use of Opiate Replacement Medication should be widely embraced. The number of people on pain medications continually increase and with it the possibility of addiction. Getting access to these mode of treatment, for example; injections which reduces use by blocking the effect of opiates, will help in significantly reducing opioids addicts. Not only should doctors be ready to provide suitable advice for these treatment methods, insurance companies should also have plans that cover such medications.

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Little pharma: The medication of U.S. children


In 2014, a study was carried out courtesy of IMS health. In this research, it was discovered that 25% of children in the U.S are on regular medications. "IMS is a pharmaceutical marketing brand whose job is to keep the $800 billion per year global pharmaceutical industry on a continued pattern of growth", source Hopefully these consultants accomplished something quite different this time around. Hopefully they provided our citizens with an overdue wake-up call.

It was noticed in the research that one in every four children residing in the U.S suffered from chronic prescriptions of medications. This research did not take in cognizance all the prescriptions that are written to treat acute illness, or the use and administration of over-the-counter products. This is indeed an outstanding number. After a careful look at the data from the research, we can conclude that either we have the sickest pediatric populations in the world or there is something that is causing the series of complaints generated from the way the therapies are driven in our healthcare system.

In their article, WSJ went ahead to discuss some of the very significant concerns generated on the situation such as how difficult it was for people to run clinical studies on children and also how trustworthy the pharmaceutical data could be, including the side effects and dosing. Some of these results were drawn from the adult population and applied to the case of children. This reason alone calls for a situation to doubt the authenticity of the results produced since it is quite confusing.

In the U.S, one in four children is on chronic medications!

Data generated from the research carried out by the IMS Health has revealed that 6.5 million children are on antipsychotics, 10 million on antidepressants, 24 millions on ADHD and 45 million are suffering from asthma. There are also some figures showing children that suffer from or use medications for sleep aids, antihypertensives, Type 2 diabetes and high cholesterol, and the list keeps getting more and more complex.

At this juncture, it will be normal if we pause to ask ourselves some vital questions;

  • Is there a need to doubt the integrity of the diagnostic criteria used in reaching these conclusions? No.
  • Do we have any reason to question the prescription of these medications know if they are really designed for the condition or not? Yes.
  •  Is it true that the doctors rely on the diagnosis and treatment free of bias and conflict of interests? NO.
  • Is there any way our third party insurers reimburse the psychologists and physicians in a manner that mood disorders, attentional conditions and other medical conditions in the psychoeducational realm are likely to be evaluated and controlled by the most appropriate professionals? NO.

A careful look at the situation at hand revealed to us that, most of the children are benefiting from the long term medications. These medications can be life changing for the child in question.



If we must take a careful look at the ongoing healthcare debate in the country, then there is a great need to take a close look at their consequences too. This is because these data from the pharmaceutical industry shows the degree to which we medicate our children’s way to health.

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Giving Newborns Medicine is a Dangerous Guessing Game. Can we make it safer?


Medication for newborns is rapidly becoming a growing concern globally. About ninety percent of drugs administered to newborns (premature and full term infants less than twenty eight days old) are not approved by the Food and Drug administration (FDA). This means that medication given to infants have not been tested for correct dosage, safety and ho effective they are.

This is mainly caused by the fear of testing drugs on babies and the hesitation of parents to enlist their newborns for drug testing. Pharmaceutical companies while trying to avoid the risk of liability which may result from fatal mistakes in the tested babies are also reluctant to invest huge amounts of money into researching about drugs for infants because it is such a thin market.

Dr. Jonathan Davis, chief of newborn medicine, Tufts Medical Center says that admitted infants to the neonatal intensive care unit receive about sixty medication in their first month of life. Dr. Davis is presently conducting several clinical trials on newborns in his NICU. The FDA also launched two global efforts to encourage clinical trials in infants.

Most treatment prescribed by doctors for infants are usually done based on experience and how these drugs have been administered to adults. They simply dilute the dose and give it to babies which has led to disasters in the past.
The way infants absorb, metabolize and excrete drugs are different from the way adults absorb, metabolize and excrete drugs. This means prescribing drugs based on how it has worked in adults should be totally avoided when it comes to prescribing them to babies. This technique has led to several deaths in both premature and full term babies.

The Pediatric Research Equity Act of 2003 and the Best Pharmaceutical for Children Act of 2002 are two large legislative efforts to increase pediatric drug studies and were made permanent laws in 2012 with the passage of the FDA safety and Innovation Act.
These Acts have improved further studies into pediatric drugs and resulted in six hundred and fifty one drugs with revised labelling for pediatric patients.
These laws have still not been adequate enough to cover new born babies, only twenty four drugs had their labels revised which either showed that they were not to be used for infants or there were safety issues. These drugs do not fall into the category of recently used drugs according to an analysis of the NICUs carried out in the United States in 2017.

Despite the urgency and criticality of these issues, there has been no major change or research into finding medicine that have been proven to be safe for newborns. The National Institutes of Health initiative invested largely into a study that covers drugs in children but recently ran out of funds while other pharmaceutical companies avoid such studies because of constraints such as; limited blood samples, fragility and the possibility of causing permanent injury in the tested newborns.
With continued awareness and sensitivity to the issue, doctors would still have to continue based on guesswork in administering medication until an alternative arrives.

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Read This before You Use an Online Pharmacy


Internet drug stores have proven to be a viable option in saving cash or getting rid of unnecessary stress. However, the use of an online drug store can possibly raise convoluted situations that will one way or the other creates health problems for you. Read the information below before embarking on a journey of dealing on the internet for medications. More info:

Compromised Privacy

Lots of consumers are mainly on the internet drug store because they are peculiar about keeping their privacy intact, this is because they do not want to have to share their health problems with the physician or discuss about their choice of medication. “Getting in line to begin a conversation like that seems so hard however; the next choice of action may be even more dangerous” argues the director of the alliance for safe online pharmacies Libby Baney.

Most of the time online drug store that are outside the soil of the United States promises to give patients medicine without asking for prescription. That genuinely speaks danger. Medications bought on the internet without the need for prescription is lacking authenticity. These medications are mostly without an active ingredient or many times they may even contain more dangerous ingredients, says Baney.

A report stated by National Association of Boards of pharmacy argues that 96% of the various internet drug stores are not in line with the federal and state laws required for the adequate safety of users and or patients. The report clearly stated that the medications shopped for on the internet are found wanting when we talk about originality.

To add to the danger that comes with shopping online for drugs there are laws that actually bind against shopping medications online outside the United States of America. It is against the law to:

·        Purchase controlled medications without a written prescription given by a medical doctor that knows your medical history and have previously have you assessed. Medications like sleeping pills, stimulants and narcotic painkillers are all illegal to purchase online from stores outside the U.S.

·        Purchase medications that do not have the approval of the Food and drug administration (FDA) while you are on the United States soil, no matter how legal it is in the purchasing country.

Standard internet drug store will request for prescription for any medication being ordered. A safe transaction of medication online should be from a verified pharmacy and should require a prescription.

The mail order drug store alternative

Prescribed medications are often expensive says the 24% of people that consumes prescribed medications, a report by Kaiser Family Foundation. So there are no surprises that consumers are looking for ways to buy cheap drugs.

It’s possible to get good prices online however; there are other ways to cash saving and convenience.

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Lifestyle Changes vs Medication When Each Is Right


At one point or the other, people decide to get serious with their health and require help with . But after making assessments in the usual manner, it is often easy to find that they aren't serious, committed or even motivated. While they may not seem like it, you often find that they miss medications even when they know they have chronic disease risk factors. For some they may have not tolerated the medications well and would need to explore other options.


The other options for such patients are quite readily available as different Associations and Organizations all recommend lifestyle changes such as weight control, exercise and diet as the first approach to lowering cholesterol. Such method is referred to as therapeutic lifestyle changes, TLC.


An emphasis has been placed on TLC by the American Diabetes Association for both the management and prevention of diabetes. Although medication is often used in the case of management. TLC has also been recommended by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure as the first and best methods for managing elevated blood pressure.


Even the American Cancer Society recommends TLC and it's evident that the dietary recommendations of these groups overlap. The emphasis in these recommendations is on foods that minimally processed, close to nature and rich in nutritional value. Foods like beans, fruits, nuts, vegetables, whole grains and many more. Weight control, regular physical activity at a moderate level that is one of the gradual results of being active and eating well are also part of the recommendations.


There is ample evidence to the fact that this basic approach really works when religiouslg followed. The Diabetes Prevention Program showed that TLC was about twice as effective as the use of the drug metformin in trying to prevent diabetes in high-risk individuals and essentially reducing its occurrence by 58%.


This shows that there is nothing radical at all in patients who are reticent about taking medications if they try to modify cardiometabolic risk using a lifestyle intervention. When you do this with the assistance of your doctor, the results are usually gratifying. You could lose credible weight by making sustainable and sensible changes to your physical activity patterns and diet. It is possible that the weight loss experienced at first may not reflect the gain of muscle and loss of body fat if you're exercising vigorously.


TLC usually won't work due to lack of follow through but works well enough when adopted well.


There is really no question in the scientific literature that body fat loss can seriously be more than weight loss in people who are exercising and gaining muscle. TLC works in a slower fashion when compared to statins or antihypertensives but at the end it is safer and more potent. Lifestyle can help to reduce chronic disease risk by almost 80% and no single drug can come close to that. But of course, medication should be used when TLC isn't bringing results as expected for any reason.

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Generic drugs have been hailed for the impact they have had on the United States healthcare industry. These group of medicines has ensured that Americans have access to affordable yet qualitative prescription medicine, thereby ensuring improved healthcare delivery.

At its most basic, a generic drug is a copy or replica of a brand-name drug, dispensed with the same dosage, intended use, effects and side effects, route of administration, risks, safety, and strength as the original (patented) drug. Unlike the original medication, a generic drug enters the market at much less a cost compared to that for a brand name due to lower production costs and less stringent regulatory approval routes/paths.

These characteristics of a generic drug mean that the market teems with a lot of producers of this brand of medicine. That many players mean that competition is steep in the generic drug market. And this competition is put putting downward pressure on the pricing of generic drugs in the market. The latest quarterly results of two leading generic drug manufacturers, Impax and Perrigo, lay credence to the fact. These companies missed revenue expectations by at least 20 percent. Overall, the generic drug sector anticipates that prices will fall by as much as 9 percent in the current year. Some enthusiasts also opine that generic drug prices will continue to experience accelerated deflation in the first half of 2017.

This brings us to the question of why is the case with the pricing mechanism of generic medicine in the United States and the rest of the world.


It is important to note that US Food and Drug Administration (FDA) has made generic medicine production/facilitation as well as market price equalization, one of its key focuses. So if generic drugs receive such enormous official goodwill, why does a downward spiral in price still occur?

We may need to look at the kind of generic medications that obtain regulatory approval in the first place. The number of Abbreviated New Drug Applications (ANDAs) which are termed ‘first timers’ has steadily decreased over the years. A first time ANDA is a generic medicine made from an original that had no copies before. In other words, the FDA is approving more generics in a market already brimming with similar copycats and fewer approvals going out for innovator generic medicines. Simple Economic logic shows that the more available a product/service is, the lower the cost of the product/service in question.

Another factor in falling generic drug pricing borders on the activities of wholesalers. These actors wield influence by engaging in a pricing war, by offering better pricing to pharmacies, rather than to national supply chains. At the same time, these wholesalers also arm twist drug manufacturers into giving them better bargains on drug pricing.

A way out?

A plausible solution to stemming the tide of falling generic drug pricing might lie in innovation. But that seems highly unlikely given the nature of the generic drug industry. A more practical (workable) solution looks to be generic drug manufacturers coming together to consolidate the market. This consolidation could eventually make the market attractive and profitable enough for investors to provide additional funding and improved capacity.





Generic Drugs Differences and Benefits


Generic drugs are usually cheaper than their brand name counterparts and that's one of the reasons why people sometimes like to settle for it. Generic medications are designed and structured to function the same way as an approved brand named drug.


They work the same way in terms of safety, strength, stability, dosage form, performance characteristics, quality, and route of administration. Both generic drugs and brand name drugs use the same active ingredients and so they have the same benefits and risks. So in essence, a generic medicine is a brand name drug that uses a different name so it's safe to say they work just the same as Brand name medicines.



Differences between generic drugs and brand name drugs


Slight differences are allowed between generic drugs and brand name drugs as far as they is no change in the way the generic drugs work or its safety when used. Visit to:


There might be changes in their inactive ingredients and the way it looks but its underlying active ingredients are preserved. Therefore, Generic drugs could differ in how it is packaged and its labeling because it does not affect how the drug works.


It can also vary from its brand name counterpart when it comes to color and shape. Another major area where generic drugs can be found to be dififrom brand name drugs are in the inactive ingredients used such as in preservatives and flavoring.


However, the FDA must have approved these inactive ingredients as as safe before it can be allowed in a generic drug. Although generic drugs might also have a different expiration date when compared to brand name drugs, it must be shown that it can keep its effectiveness before it reaches its expiry date just like the brand name product.




Benefits of generic drugs


  • Generic drugs are less expensive

    Like we said earlier, one of the subtle but major reasons why so many people buy generic drugs is because they are way cheaper than Brand name drugs.

    The reason why this possible is because generic drugs do not have to do all the testing and research that brand name drug manufacturers usually do before they get approved. They only need to copy the drug formula that already exists and this saves them the cost and by extension allowing the drug price to stay low.

  • They are bioequivalent and have the same quality

    When it comes to the biological composition of the drugs, generic drugs must be bioequivalent to the brand name drug. FDA has strict guidelines concerning the quality of composition for generic drugs and generic drug manufacturers must show that the drug is bioequivalent.

    In essence, this means that the same dosage of active ingredients of the generic drug that is delivered to the body at the same time can be used by the body just in the same way as the brand name drug

    Before any generic drug can be approved by the FDA, there are a set of stringent guidelines that must be met as well as other research that must be done to prove the bioequivalence with its brand name counterpart.

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Treatment Acinetobacter baumannii Infections


Acinetobacter baumannii: Epidemiology, Antimicrobial Resistance, and Treatment Options


Multidrug-resistant Acinetobacter baumannii is recognized to be among the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. Increasing antimicrobial resistance among Acinetobacter isolates has been documented, although definitions of multidrug resistance vary in the literature. A. baumannii survives for prolonged periods under a wide range of environmental conditions. The organism causes outbreaks of infection and health care–associated infections, including bacteremia, pneumonia, meningitis, urinary tract infection, and wound infection. Antimicrobial resistance greatly limits the therapeutic options for patients who are infected with this organism, especially if isolates are resistant to the carbapenem class of antimicrobial agents. Because therapeutic options are limited for multidrug-resistant Acinetobacter infection, the development or discovery of new therapies, well-controlled clinical trials of existing antimicrobial regimens and combinations, and greater emphasis on the prevention of health care–associated transmission of multidrug-resistant Acinetobacter infection are essential. Visit to:



Risk factors for colonization or infection with multidrug-resistant Acinetobacter species include prolonged length of hospital stay, exposure to an intensive care unit (ICU), receipt of mechanical ventilation, colonization pressure, exposure to antimicrobial agents, recent surgery, invasive procedures, and underlying severity of illness [1, 3]. Widespread environmental contamination is often demonstrated, and outbreaks of infection have been traced to respiratory care equipment, wound care procedures, humidifiers, and patient care items [4–13]. Wilks et al. [8] reported a recent outbreak of multidrug-resistant Acinetobacter infection, with environmental contamination found on curtains, laryngoscope blades, patient lifting equipment, door handles, mops, and keyboards. Medical equipment has been implicated, emphasizing the need for special attention to disinfection of shared items and extra caution with respiratory care and wound care procedures [4, 5, 7]. One or more epidemic Acinetobacter clones often coexist with endemic strains, making it difficult to detect and control transmission.


Symptoms of Acinetobacter infection

Acinetobacter causes a variety of diseases, ranging from pneumonia to serious blood or wound infections, and the symptoms vary depending on the disease. Acinetobacter may also “colonize” or live in a patient without causing infection or symptoms, especially in tracheostomy sites or open wounds.


Transmission of Acinetobacter infection

Acinetobacter poses very little risk to healthy people. However, people who have weakened immune systems, chronic lung disease, or diabetes may be more susceptible to infections with Acinetobacter. Hospitalized patients, especially very ill patients on a ventilator, those with a prolonged hospital stay, those who have open wounds, or any person with invasive devices like urinary catheters are also at greater risk for Acinetobacter infection. Acinetobacter can be spread to susceptible persons by person-to-person contact or contact with contaminated surfaces.


Prevention of Acinetobacter infection

Acinetobacter can live on the skin and may survive in the environment for several days. Careful attention to infection control procedures, such as hand hygiene and environmental cleaning, can reduce the risk of transmission.



Carbapenems. Increasing antimicrobial resistance leaves few therapeutic options, and there are no well-designed clinical trials to compare treatment regimens for multidrug-resistant Acinetobacter infection. Available data are from in vitro, animal, and observational studies. Carbapenems remain the treatment of choice if isolates retain susceptibility to this antimicrobial class. The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance program has documented discordance that favors imipenem as the more potent agent, compared with meropenem, for treatment of multidrug-resistant Acinetobacter infection [78, 79]. The converse result was reported in Greece [80]. Efflux pumps may affect meropenem to a greater degree, whereas specific ²-lactamases hydrolyze imipenem more efficiently [80]. Susceptibility testing of imipenem does not predict susceptibility to meropenem or vice versa [78]. Unfortunately, carbapenem-resistant Acinetobacter isolates are increasingly reported worldwide.

²-Lactamase inhibitors. ²-Lactamase inhibitors, particularly sulbactam, have intrinsic activity against many Acinetobacter strains. The presence of a ²-lactam agent (e.g., ampicillin) in combination with the ²-lactamase inhibitor does not appear to contribute activity or synergy [81, 82]. Monotherapy with sulbactam is not recommended for severe Acinetobacter infection. However, Wood et al. [83] reported successful use of sulbactam to treat 14 patients with multidrug-resistant Acinetobacter ventilator-associated pneumonia, finding no difference in clinical outcomes between sulbactam-treated patients and 63 patients who received imipenem. Levin et al. [84] reported a cure rate of 67% using ampicillin-sulbactam to treat carbapenem-resistant Acinetobacter infection, but good patient outcomes were associated with lower severity of illness. The results of antimicrobial susceptibility tests (e.g., with agar dilution or the Etest) of ²–lactam/²-lactamase combinations at fixed concentrations must be interpreted with caution, because they may indicate susceptibility when an isolate is actually resistant [82].

Tigecycline. Tigecycline, a relatively new glycylcycline agent, has bacteriostatic activity against multidrug-resistant Acinetobacter species [85, 86]. High-level resistance to tigecycline has been detected among some multidrug-resistant Acinetobacter isolates, and there is concern that the organism can rapidly evade this antimicrobial agent by upregulating chromosomally mediated efflux pumps [68, 87–91]. Peleg et al. [89] reported 2 cases of multidrug-resistant Acinetobacter bacteremia that occurred while patients were receiving tigecycline for another indication. Two recent studies documented overexpression of a multidrug efflux pump in Acinetobacter isolates with decreased susceptibility to tigecycline [92, 93]. Given these findings and concern about whether adequate peak serum concentrations can be achieved, tigecycline is best reserved for salvage therapy, with administration determined in consultation with an infectious diseases specialist [89].

Aminoglycosides. Aminoglycoside agents, such as tobramycin and amikacin, are therapeutic options for infection with multidrug-resistant Acinetobacter isolates that retain susceptibility. These agents are usually used in conjunction with another active antimicrobial agent. Many multidrug-resistant Acinetobacter isolates retain intermediate susceptibility to amikacin or tobramycin; resistance to this class of agents is increasingly associated with aminoglycoside-modifying enzymes or efflux pump mechanisms.

Polymyxin therapy. Given limited therapeutic options, clinicians have returned to the use of polymyxin B or polymyxin E (colistin) for the most drug-resistant Acinetobacter infections [94, 95]. Colistin acts by disturbing the bacterial cell membrane, thus increasing permeability, leading to cell death [94]. Colistin is bactericidal against Acinetobacter species, and its effect is concentration dependent [95]. Resistance to polymyxins has been reported, possibly as a result of outer cell membrane alterations or an efflux pump mechanism [65, 66, 94, 95]. Observational studies have reported rates of cure or improvement for colistin of 57%–77% among severely ill patients with multidrug-resistant Acinetobacter infections, including pneumonia, bacteremia, sepsis, intra-abdominal infection, and CNS infection [96–99]. Although high-quality pharmacokinetic data are lacking, colistin is reported to have relatively poor lung and CSF distribution, and clinical outcomes vary for different types of infections [96]. Despite an overall “good outcome” rate of 67%, Levin et al. [96] found a lower response rate of 25% for patients with pneumonia due to multidrug-resistant, gram-negative bacilli who were treated with parenteral colistin. Other studies have reported more favorable clinical response rates (56%–61%) for parenteral colistin treatment of multidrug-resistant Acinetobacter ventilator-associated pneumonia [100–103].

There are case reports of successful treatment of multidrug-resistant Acinetobacter meningitis with parenteral colistin, but its efficacy for this condition remains unclear [104, 105]. Several case reports and case series report the use of intraventricular or intrathecal polymyxin therapy, with or without parenteral therapy, for the treatment of gram-negative bacterial meningitis [104, 106–108]. A recent review of 31 reports involving 64 episodes of gram-negative bacterial meningitis found a cure rate of 80%, including cure for 10 (91%) of 11 patients with Acinetobacter meningitis [109]. The majority of patients received systemic antimicrobial therapy in addition to local administration of polymyxin. Neurologic toxicity occurred primarily in reports published before 1970, and the most common manifestation was meningeal irritation, which was apparently dose-dependent and reversible [109]. Overall, there is insufficient evidence to draw conclusions regarding the efficacy, safety, or pharmacokinetic properties of colistin for treatment of CNS infection, although it remains an important option for salvage therapy [104].

Data are lacking on the pharmacokinetics, pharmacodynamics, and toxicodynamics of colistin. Earlier methods of measuring serum concentrations of the drug were unable to adequately distinguish concentrations of colistimethate, the nonactive prodrug, from concentrations of colistin [95]. There are inconsistencies among manufacturers regarding the recommended dosing of colistin and the units of measurement employed [95]. Data suggest that current recommended dosing regimens may lead to serum levels of colistin that are less than the MIC for Acinetobacter infection [95]. These problems highlight the need for careful pharmacologic studies and the importance of attention to formulation and dosing in clinical care and research studies.

Synergy and combination therapy. A lack of controlled clinical trials makes it difficult to evaluate the role of synergy or combination therapy for multidrug-resistant Acinetobacter infection. Most available data are from uncontrolled case series, animal models, or in vitro studies. The studies summarized in table 2 investigated various combinations of rifampin, sulbactam, aminoglycoside agents, colistin, carbapenems, and other agents against multidrug-resistant Acinetobacter infection [102, 110–123].

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